bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood pressure variability compromises vascular function in middle-aged mice
Authors: Mendiola Perenkita J. , O’Herron Philip , Xie Kun , Brands Michael W. , Bush Weston , Patterson Rachel E. , Di Stefano Valeria , Filosa Jessica A.
Published: October 2024

Blood pressure variability (BPV) has emerged as a novel risk factor for cognitive decline and dementia, independent of alterations in average blood pressure (BP). However, the underlying consequences of large BP fluctuations on the neurovascular complex are unknown. We developed a novel mouse model of BPV in middle-aged mice based on intermittent Angiotensin II infusions. Using radio telemetry, we demonstrated that the 24-hr BP averages of these mice were similar to controls, indicating BPV without hypertension. Chronic (20-25 days) BPV led to a blunted bradycardic response and cognitive deficits. Two-photon imaging of parenchymal arterioles showed enhanced pressure-evoked constrictions (myogenic response) in BPV mice. Sensory stimulus-evoked dilations (neurovascular coupling) were greater at higher BP levels in control mice, but this pressure-dependence was lost in BPV mice. Our findings support the notion that large BP variations impair vascular function at the neurovascular complex and contribute to cognitive decline.
The relationship between health literacy and adherence to physical activity guidelines: a scoping review
Authors: Lawrence Alex , Wardle Jon , Yoxall Jacqui Susan
Published: October 2024

Objective

To examine the relationship between health literacy and adherence to physical activity guidelines.

Methods

In line with the Joanna Briggs Institute framework, we conducted a scoping review of the literature.

Results

Out of 2,098 articles identified, 19 met the inclusion criteria. The studies utilised various health literacy measurement tools, with the European Health Literacy Survey being used the most. Fifteen studies examined the association between total health literacy scores and achieving >150 minutes of moderate-to-vigorous physical activity weekly. Nine studies reported a positive association, while others found no significant association. In particular, studies using self-reported physical activity more frequently found an association, whereas no association was found when using objective physical activity measures.

Conclusions

The findings of this review were inconclusive. The lack of standard health literacy instruments and reporting presents a barrier to the field of knowledge progressing. Moreover, longitudinal relationships between health literacy, mediators and physical activity need to be investigated.
Strengthening Phage Resistance of Streptococcus thermophilus by Leveraging Complementary Defense Systems
Authors: Leprince Audrey , Lefrançois Justine , Magill Damian , Horvath Philippe , Romero Dennis , Rousseau Geneviève M. , Moineau Sylvain
Published: October 2024

CRISPR-Cas and restriction-modification systems represent the core defense arsenal in Streptococcus thermophilus to block lytic phages, but their effectiveness is compromised by phages encoding anti-CRISPR proteins (ACRs) and other counter-defense strategies. Here, we explored the resistome of 263 S. thermophilus strains to uncover other anti-phage systems. The defense landscape of S. thermophilus was enriched by 21 accessory defense systems, 13 of which had not been previously investigated in this species. Experimental validation of 17 systems with 14 phages showed varying anti-phage levels, uncovering intra-genus specificities among the five viral genera infecting S. thermophilus. Interestingly, the resistance levels were even higher when some defense systems (Dodola and PD-Lambda-1) were expressed from a low-copy plasmid or when integrated into the chromosome. We also observed a synergistic effect when combining Gabija with CRISPR-Cas, underscoring the potential of these additional defense systems for developing more robust industrial S. thermophilus strains, particularly against ACR-encoding phages.
Structural basis for a dual-function type II-B CRISPR-Cas9
Authors: Hibshman Grace N. , Taylor David W.
Published: October 2024

Cas9 fromStreptococcus pyogenes(SpCas9) revolutionized genome editing by enabling programmable DNA cleavage guided by an RNA. However, SpCas9 tolerates mismatches in the DNA-RNA duplex, which can lead to deleterious off-target editing. Here, we reveal that Cas9 fromFrancisella novicida(FnCas9) possesses a unique structural feature—the REC3 clamp—that underlies its intrinsic high-fidelity DNA targeting. Through kinetic and structural analyses, we show that the REC3 clamp forms critical contacts with the PAM-distal region of the R-loop, thereby imposing a novel checkpoint during enzyme activation. Notably,F. novicidaencodes a non-canonical small CRISPR-associated RNA (scaRNA) that enables FnCas9 to repress an endogenous bacterial lipoprotein gene, subverting host immune detection. Structures of FnCas9 with scaRNA illustrate how partial R-loop complementarity hinders REC3 clamp docking and prevents cleavage in favor of transcriptional repression. The REC3 clamp is conserved in type II-B CRISPR-Cas9 systems, pointing to a potential path for engineering precise genome editors or developing novel antibacterial strategies. These findings reveal the dual mechanisms of high specificity and virulence by FnCas9, with broad implications for biotechnology and therapeutic development.

Graphical Abstract
HuR-dependent expression of RyR2 contributes to calcium-mediated thermogenesis in brown adipocytes
Authors: Guarnieri Adrienne R. , Anthony Sarah R. , Acharya Pooja , Wen Bo Yao , Lanzillotta Lindsey , Gavin Rylie , Tranter Michael
Published: October 2024

Several uncoupling protein 1 (UCP1)-independent thermogenic pathways have been described in thermogenic adipose tissue, including calcium-mediated thermogenesis in beige adipocytes via sarco/endoplasmic reticulum ATPase (SERCA). We have previously shown that adipocyte-specific deletion of the RNA binding protein human antigen R (HuR) results in thermogenic dysfunction independent of UCP1 expression. RNA sequencing revealed the downregulation of several genes involved in calcium ion transport upon HuR deletion. The goal of this work was to define the HuR-dependent mechanisms of calcium driven thermogenesis in brown adipocytes.

We generated (BAT)-specific HuR-deletion (BAT-HuR-/-) mice and show that their body weight, glucose tolerance, brown and white adipose tissue weights, and total lipid droplet size were not significantly different compared to wild-type. Similar to our initial findings in Adipo-HuR-/-mice, mice with BAT-specific HuR deletion are cold intolerant following acute thermal challenge at 4°C, demonstrating specificity of acute HuR-dependent thermogenesis to BAT. We also found decreased expression of ryanodine receptor 2 (RyR2), but no changes in RyR2, SERCA1, SERCA2, or UCP1 expression, in BAT from BAT-HuR-/-mice. Next, we used Fluo-4 calcium indicator dye to show that genetic deletion or pharmacological inhibition of HuR blunts the increase in cytosolic calcium concentration in SVF-derived primary brown adipocytes. Moreover, we saw a similar blunting in β-adrenergic-mediated heat generation, as assessed by ERtherm AC fluorescence, in SVF-derived brown adipocytes following HuR inhibition or deletion. Mechanistically, we show that HuR directly binds and reduces the decay rate of RyR2 mRNA in brown adipocytes, and stabilization of RyR2 via S107 rescues β-adrenergic-mediated cytosolic calcium increase and heat generation in HuR deficient brown adipocytes.

In conclusion, our results suggest that HuR-dependent control of RyR2 expression plays a significant role in the thermogenic function of brown adipose tissue through modulation of SR calcium cycling.
ALS-associated RNA binding proteins converge onUNC13Atranscription through regulation of REST
Authors: Watanabe Yasuaki , Suzuki Naoki , Nakagawa Tadashi , Hosogane Masaki , Akiyama Tetsuya , Warita Hitoshi , Aoki Masashi , Nakayama Keiko
Published: October 2024

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Although multiple pathophysiological mechanisms have been identified, a unified molecular basis for ALS has remained elusive. The ALS-associated RNA binding protein (RBP) TDP-43 has previously been shown to stabilizeUNC13AmRNA by preventing cryptic exon inclusion. We here show that three ALS-associated RBPs—MATR3, FUS, and hnRNPA1—regulateUNC13Aexpression by targeting the silencing transcription factor REST. These three RBPs bind to and downregulateRESTmRNA and thereby promoteUNC13Atranscription. REST overexpression was detected not only in response to the loss of each of these three RBPs in cultured cells but also in motor neurons of individuals with familial or sporadic ALS. The functional convergence of four RBPs on the regulation ofUNC13A, a gene essential for synaptic transmission, highlights a pivotal contribution of these proteins to maitainance of synaptic integrity. Our findings thus provide key insight into ALS pathogenesis and a basis for the development of new therapeutic agents.
Extreme precipitation, exacerbated by anthropogenic climate change, drove Peru’s record-breaking 2023 dengue outbreak
Authors: Harris Mallory J. , Trok Jared T. , Martel Kevin S. , Borbor Cordova Mercy J. , Diffenbaugh Noah S. , Munayco César V. , Lescano Andrés G. , Mordecai Erin A.
Published: October 2024

Anthropogenic forcing is increasing the likelihood and severity of certain extreme weather events, which may catalyze outbreaks of climate-sensitive infectious diseases. Extreme precipitation events can promote the spread of mosquito-borne illnesses by creating vector habitat, destroying infrastructure, and impeding vector control. Here, we focus on Cyclone Yaku, which caused heavy rainfall in northwestern Peru from March 7th - 20th, 2023 and was followed by the worst dengue outbreak in Peru’s history. We apply generalized synthetic control methods to account for baseline climate variation and unobserved confounders when estimating the causal effect of Cyclone Yaku on dengue cases across the 56 districts with the greatest precipitation anomalies. We estimate that 67 (95% CI: 30 - 87) % of cases in cyclone-affected districts were attributable to Cyclone Yaku. The cyclone significantly increased cases for over six months, causing 38,209 (95% CI: 17,454 - 49,928) out of 57,246 cases. The largest increases in dengue incidence due to Cyclone Yaku occurred in districts with a large share of low-quality roofs and walls in residences, greater flood risk, and warmer temperatures above 24°C. Analyzing an ensemble of climate model simulations, we found that extremely intense March precipitation in northwestern Peru is 42% more likely in the current era compared to a preindustrial baseline due to climate forcing. In sum, extreme precipitation like that associated with Cyclone Yaku has become more likely with climate change, and Cyclone Yaku caused the majority of dengue cases across the cyclone-affected districts.

Significance Statement

Anthropogenic climate change is increasing the risk of extreme events that can lead to infectious disease epidemics, but few studies have directly measured this health cost of climate change. We do so by focusing on Cyclone Yaku, which affected northwestern Peru in March 2023, and was immediately followed by a dengue epidemic. Cyclone Yaku caused 67% of cases reported over six months in the affected region. Industrial-era climate forcing has increased the likelihood of extreme March precipitation like that associated with Cyclone Yaku by 42%. Assessing the linkages between climate change, extreme weather, and outbreaks of dengue and other infectious diseases is crucial for understanding the impact that climate change has already had and preparing for future health risks.
Gene Regulatory Network Based Biomarker Transition from Normalcy to Malignancy: A study of Lung Cancer Using Differential Gene Expression Data
Authors: Mandal Supriya , Biswas Surama
Published: October 2024

Lung cancer is a global threat, and understanding its pathology through gene regulatory network (GRN)-based biomarkers could offer significant insights. In this study, GRN-based biomarkers have been constructed to demonstrate the topology shift of GRN from a normal condition to a lung cancer condition. This study employed three distinct processes to identify significant genes from differential gene expression data related to lung cancer: 1) simple variance-based screening, 2) a recent gene selection algorithm incorporating simulated annealing and a biologically inspired objective function, and 3) a volcano plot comparing log2 fold changes against -log10 P values. These comprehensive methods identified 21 common genes as significant genes, including KRT5, SFTPC, KRT16, and AKR1B10, which have strong associations with lung cancer pathology according to previous literature. To gain deeper insights into the underlying biological mechanisms, co-expression-modelled GRNs have been constructed for both normal and lung cancer conditions based on these significant genes. These networks provide a detailed visual and mathematical representation of gene interactions within the cellular environment, illustrating how these interactions differ between healthy and diseased states. The shift in network biomarker topologies from normal to diseased conditions have been closely analysed using centrality measures, which quantify the importance of genes based on their connectivity and position within the network. Notably, the pronounced change in the degree of centrality for genes such as GJB6 between normal and diseased states suggests their pivotal roles in the transition to lung cancer. Rigorous statistical and machine learning methods validated the significance of the selected genes and their interconnections, ensuring the robustness of the findings.
Mycobacterium tuberculosis-specific cytokine responses of infants born to mothers with active tuberculosis in Uganda
Authors: Sitenda Diana , Ssekamatte Phillip , Nakavuma Rose , Kyazze Andrew Peter , Bongomin Felix , Baluku Joseph , Nabatanzi Rose , Kibirige Davis , Cose Stephen , Andia-Biraro Irene , Nakimuli Annettee
Published: October 2024

Background

Immunizing infants with various vaccines, includingBacillus Calmette–Guérin(BCG), Diphtheria-Pertusis-Tetanus (DPT), and measles, aims to enhance immunity. In instances where vaccine responses have been reported to be compromised, individuals are prone to infection. The BCG vaccine, for example, induces strong type 1 immune responses, particularly interferon-gamma (IFN-γ) expression, that are essential for protection againstMycobacterium tuberculosis(Mtb). However, there is scanty evidence on whether this effect is established or sustained when infants are exposed toMtbeither in utero or after birth. We compared TB-specific cytokine responses for IFN-γ, interleukin (IL)-2 (IL-2), tumour necrosis factor-alpha (TNF-α), IL-17A, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) using supernatants harvested from QFT-Plus Blood Collection Tubes.

Methods

This cross-sectional study compared 22 infants born to mothers with bacteriologically confirmed active tuberculosis (TB), defined as TB exposed or cases, to 20 infants born to mothers without active TB, defined as TB non-exposed or controls. Plasma harvested from the QFT-plus tubes (TB1 and TB2) was used to perform a 5-plex Luminex assay using the LX 100/200 Luminex machine and measured in pg/mL. Data was analysed using R (v.4.4.1). The Mann-Whitney U test was used to determine statistical significance at a p-value less than 0.05 and a 95% confidence interval. Data was expressed as median and interquartile ranges (IQR).

Results

TB-exposed infants showed IFNγ responses were slightly higher among TB-exposed infants compared to non-exposed (Medians (IQR): 15.49 (14.58-16.49) versus 14.96 (14.60-16.60), p=0.68, respectively. There was a strong expression of total IL-17A among TB-exposed compared to non-exposed 11.91 (10.89-13.50) versus 10.69 (10.17-11.64), p=0.035. We observed no differences in IL-2, TNF, and GM-CSF responses.

Conclusion

TB exposure among infants slightly alters theirMtb-specific cytokine responses, especially IL-17A cytokine responses. This suggests possible ongoingMtbinfection among TB-exposed infants. Follow-up studies of such infants are necessary to assess their risk of future TB infection and disease and the potential need for TB chemoprophylaxis.
Electroencephalography Markers of Perinatal Depression and Anxiety in a Diverse Longitudinal Cohort: A Preliminary Study
Authors: Attre Maigh , Alvernaz Suzanne , Wenzel Elizabeth , Pettineo Abigail , Parikh Sarah , Conway Catherine , Kroeger Molly , Ajilore Olu , Maki Pauline , Leow Alex , Bernabé Beatriz Peñalver
Published: October 2024

Perinatal mental health disorders, such as depression and anxiety, are highly prevalent and can have severe consequences on maternal morbidity and mortality, and on infant neurodevelopment. Yet, the biological mechanisms of these disorders are underexplored, especially in Black, Indigenous, and People of Color (BIPOC) populations. Here, we aim to investigate functional brain alterations across the perinatal period using portable electroencephalography (pEEG) in a diverse cohort of pregnant individuals reporting symptoms of depression or anxiety. Participants (61 subjects, 45% Non-Hispanic Black and 32% Hispanic) were followed longitudinally from early pregnancy through postpartum. Brain electrical activity was quantified with pEEG (61 subjects, 209 pEEG recordings) and mental health was assessed using the PHQ-9 and GAD-7 at multiple time points throughout the perinatal period. Using linear models and linear mixed models, our preliminary findings suggest significant changes in brain wave activity, such as alpha and delta waves, are associated with depression and anxiety severity during the perinatal period. The study addresses critical gaps in understanding perinatal mental health in racially, ethnically, and socioeconomically diverse populations, with the goal of developing sensitive clinically feasible diagnostic tools to mitigate health disparities.
Development and validation of the TabCAT-EXAMINER: tablet-based executive functioning factor score for research and clinical trials
Authors: Sanderson-Cimino Mark , Possin Katherine L. , Mungas Dan M. , Paolillo Emily W. , Asken Breton M. , Tsoy Elena , Jarrott Sabrina , Cobigo Yann , Saloner Rowan , Casaletto Kaitlin B. , Considine Ciaran , Fields Julie A. , Molden Joie , Rascovsky Katya , Weintraub Sandra , Wong Bonnie , Heuer Hilary W. , Forsberg Leah K. , Rojas Julio C. , VandeVrede Lawren , Ljubenkov Peter , Rabinovici Gil D. , Gorno-Tempini Maria L. , Seeley William W. , Miller Bruce L. , Boeve Bradley F. , Rosen Howard J. , Boxer Adam L. , Rankin Katherine P. , Kramer Joel H. , Staffaroni Adam M.
Published: October 2024

Objective

The National Institute of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) is a validated laptop-based battery of executive functioning tests. A modified tablet version of the EXAMINER was developed on the UCSF Tablet-based Cognitive Assessment Tool (TabCAT-EXAMINER). Here we describe the battery and investigate the reliability and validity of a composite score.

Methods

A diagnostically heterogeneous sample of 2135 individuals (mean age=65.58, SD=16.07), including controls and participants with a variety of neurodegenerative syndromes completed the TabCAT-EXAMINER. A composite score was developed using confirmatory factor analysis and item response theory. Validity was evaluated via linear regressions that tested associations with neuropsychological tests, demographics, clinical diagnosis, and disease severity. Replicability of cross-sectional results was tested in a separate sample of participants (n=342) recruited from a Frontotemporal dementia study. As this separate sample also collected longitudinal TabCAT-EXAMINER measures, we additionally assessed test-retest reliability and associations between baseline disease severity and changes in TabCAT-EXAMINER scores.

Results

The TabCAT-EXAMINER score was normally distributed, demonstrated high test-retest reliability, and was associated in the expected directions with independent tests of executive functioning, demographics, disease severity, and diagnosis. Greater baseline disease severity was associated with faster longitudinal TabCAT-EXAMINER decline.

Conclusions

The TabCAT-EXAMINER is a tablet-based executive functioning battery developed for observational research and clinical trials. Performance can be summarized as a single composite score, and results of this study support its reliability and validity in cognitive aging and neurodegenerative disease cohorts.
Modulation of leg trajectory by transcranial magnetic stimulation during walking
Authors: Bourgeois H. , Guay-Hottin R. , Meftah E.-M. , Martinez M. , Bonizzato M. , Barthélemy D.
Published: October 2024

The primary motor cortex is involved in initiation and adaptive control of locomotion. However, the role of the motor cortex in controlling gait trajectories remains unclear. In animals, cortical neuromodulation allows for precise control of step height. We hypothesized that a similar control framework applies to humans, whereby cortical stimulation would primarily increase foot elevation.

Transcranial magnetic stimulation (TMS) was applied over the motor cortex to assess the involvement of the corticospinal tract over the limb trajectory during human walking. Eight healthy adults (aged 20-32 years) participated in treadmill walking at 1.5 km/h. TMS was applied over the left motor cortex at an intensity of 120% of the threshold to elicit a dorsiflexion of the right ankle during the swing phase of gait. Electromyographic (EMG) measurements and three-dimensional (3D) lower limb kinematics were collected.

When delivered during the early swing phase, TMS led to a significant increase in the maximum height of the right toe by a mean of 40.7% ± 14.9% (25.6mm ± 9.4 mm, p = 0.0352) and knee height by 57.8%± 16.8%; (32mm ± 9.3 mm; p = 0.008) across participants.

These findings indicate that TMS can influence limb trajectory during walking, highlighting its potential as a tool for studying cortical control of locomotion.
SC10X/U: A High-density Electrode System for Non-Invasive Recording of Neural Activity of the Cervical Spinal Cord
Authors: Mehra Prabhav , Metzger Marjorie , Bista Saroj , Plaitano Serena , Giglia Eileen R. , Nash Leah , Domhnaill Éanna Mac , Mitchell Matthew , Bede Peter , Lowery Madeleine , Muthuraman Muthuraman , Hardiman Orla , Nasseroleslami Bahman
Published: October 2024

Objective

To design and develop a high-density (HD) electrode system that describes the position of surface electrodes for recording electrophysiological signals from the human cervical spinal cord. The system is intended to standardize experimental recordings and facilitate the subsequent analysis of evoked and spontaneous spinal cord neural activity, using high-density electrospinography (HD-ESG).

Method

The proposed system (SC10-X/U) describes the locations of up to 76 channels with a unique nomenclature, where the division of the spinal cord (SC) electrode space was inspired by the EEG 10-10 system. As proof of concept, spinal evoked potentials in response to median nerve stimulation at the wrist were recorded from 10 participants and characterized based on a 64-channel derivation from the SC10-X/U system.

Results

Following the design criteria, the SC10-X/U defines 76 electrode positions and its configuration. HD-ESG system was utilized to successfully record evoked spinal responses and significant N13 and P9 potential were observed in response to the stimulation. The spinal N13 potential had a latency of 13.2 +-1.1ms (mean +-SD) after stimulation. A topographic map of the N13 electro-spinal activity using the 64-channel recording system revealed an epicentre at C5-C7 dorsal-vertebral locations (ML4 - ML6 electrodes).

Conclusion

The proposed SC10-X/U system will facilitate standardized recording and analysis of high-density ESG signals from the human cervical spinal cord. The system defines electrode locations to promote standardization across different individuals, studies, and clinical and research centres. The HD-ESG evoked potentials recorded using the proposed system were comparable to those observed in previous non-HD studies. The presented topographic maps conform to known neurophysiological and neuroanatomical findings. This served to validate the design and development of the electrode system and patch for future studies.
Lack of neuroprotection after systemic administration of the soluble TNF inhibitor XPro1595 in an rAAV6-α-Syn+PFFs-induced rat model for Parkinson’s disease
Authors: Fredlund Filip , Fryklund Claes , Trujeque-Ramos Olivia , Staley Hannah A. , Pardo Joaquin , Luk Kelvin C. , Tansey Malú G. , Swanberg Maria
Published: October 2024

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration, α-Synuclein (α-Syn) pathology, and inflammation. Microglia in the substantia nigra pars compacta (SNpc) upregulate major histocompatibility complex class II (MHCII), and variants in genes encoding MHCII affect PD risk. Additionally, elevated TNF levels and α-Syn-reactive T cells in circulation suggest a strong link between innate and adaptive immune responses in PD. We have previously reported that reduced levels of the class II transactivator, the master regulator of MHCII expression, increases susceptibility to α-Syn-induced PD-like pathology in rats and are associated with higher serum levels of soluble TNF (sTNF). Here, we demonstrate that inhibiting sTNF with a dominant-negative TNF variant, XPro1595, known to be neuroprotective in endotoxin- and toxin-induced neurodegeneration models, fails to protect against robust α-Syn-induced PD-like pathology in rats. We used a model combining rAAV-mediated α-Syn overexpression in SNpc with striatal injection of α-Syn preformed fibrils two weeks later. Systemic XPro1595 treatment was initiated one-week post-rAAV-α-Syn. We observed up to 70% loss of striatal dopaminergic fibers without treatment, and no protective effects on dopaminergic neurodegeneration after XPro1595 administration. Pathological α-Syn levels as well as microglial and astrocytic activation were not reduced in SNpc or striatum following XPro1595 treatment. An increase in IL-6 and IL-1β levels in CSF was observed in rats treated with XPro1595, possibly explaining a lack of protective effects following treatment. Our results highlight the need to determine the importance of timing of treatment initiation, which is crucial for future applications of sTNF therapies in PD patients.
Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness
Authors: Dai Rui , Jang Hyunwoo , Hudetz Anthony G. , Huang Zirui , Mashour George A.
Published: October 2024

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.
RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa
Authors: Chandler Laurel C. , Gardner Apolonia , Cepko Constance L.
Published: October 2024

Retinitis pigmentosa (RP) is the most common cause of inherited retinal degeneration worldwide. It is characterized by the sequential death of rod and cone photoreceptors, the cells responsible for night and daylight vision, respectively. Although mutations in RP are mostly rod-specific, there is a secondary degeneration of cones. One possible mechanism behind cone death is metabolic dysregulation. Photoreceptors are highly metabolically active, consuming large quantities of glucose and producing substantial amounts of lactate. The retinal pigment epithelium (RPE) mediates the transport of glucose from the blood to photoreceptors and, in turn, removes lactate, which it can use as its own source of fuel. The model for metabolic dysregulation in RP suggests that, following the death of rods, lactate levels are substantially diminished causing the RPE to withhold glucose, resulting in nutrient deprivation for cones. Here, we present adeno-associated viral vector-mediated delivery of monocarboxylate transporter 2 (MCT2) into RPE cells with the aim of promoting lactate uptake from the blood and encouraging the passage of glucose to cones. We demonstrate prolonged survival and function of cones in rat and mouse RP models, revealing a possible gene agnostic therapy for preserving vision in RP. We also present the use of fluorescence lifetime imaging-based biosensors for lactate and glucose within the eye. Using this technology, we show changes to lactate and glucose levels within MCT2-expressing RPE, suggesting cone survival is impacted by RPE metabolism.
Convergent olfactory circuits for courtship inDrosophilarevealed byds-Tango
Authors: Fisher John D. , Crown Anthony M. , Sorkaç Altar , Martinez-Machado Sasha , Snell Nathaniel J. , Vishwanath Neel , Monje Silas , Vo An , Wu Annie H. , Moșneanu Rareș A. , Okoro Angel M. , Savaş Doruk , Nkera Bahati , Iturralde Pablo , Kumari Aastha , Chou-Freed Cambria , Hartmann Griffin G. , Talay Mustafa , Barnea Gilad
Published: October 2024

Animals exhibit sex-specific behaviors that are governed by sexually dimorphic circuits. One such behavior in maleDrosophila melanogaster, courtship, is regulated by various sensory modalities, including olfaction. Here, we reveal how sexually dimorphic olfactory pathways in male flies converge at the third-order, onto lateral horn output neurons, to regulate courtship. To achieve this, we developedds-Tango, a modified version of the monosynaptic tracing and manipulation tooltrans-Tango. Inds-Tango, two distinct configurations oftrans-Tango are positioned in series, thus providing selective genetic access not only to the monosynaptic partners of starter neurons but also to their disynaptic connections. Usingds-Tango, we identified a node of convergence for three sexually dimorphic olfactory pathways. Silencing this node results in deficits in sex recognition of potential partners. Our results identify lateral horn output neurons required for proper courtship behavior in male flies and establishds-Tango as a tool for disynaptic circuit tracing.
Touchscreen response precision is sensitive to the explore/exploit tradeoff
Authors: Mueller Dana , Giglio Erin , Chen Cathy S. , Holm Aspen , Ebitz R. Becket , Grissom Nicola M.
Published: October 2024

The explore/exploit tradeoff is a fundamental property of choice selection during reward-guided decision making. In perceptual decision making, higher certainty decisions are more motorically precise, even when the decision does not require motor accuracy. However, while we can parametrically control uncertainty in perceptual tasks, we do not know what variables - if any - shape motor precision and reflect subjective certainty during reward-guided decision making. Touchscreens are increasingly used across species to measure choice, but provide no tactile feedback on whether an action is precise or not, and therefore provide a valuable opportunity to determine whether actions differ in precision due to explore/exploit state, reward, or individual variables. We find all three of these factors exert independent drives towards increased precision. During exploit states, successive touches to the same choice are closer together than those made in an explore state, consistent with exploit states reflecting higher certainty and/or motor stereotypy in responding. However, exploit decisions might be expected to be rewarded more frequently than explore decisions. We find that exploit choice precision is increased independently of a separate increase in precision due to immediate past reward, suggesting multiple mechanisms regulating choice precision. Finally, we see evidence that male mice in general are less precise in their interactions with the touchscreen than females, even when exploiting a choice. These results suggest that as exploit behavior emerges in reward-guided decision making, individuals become more motorically precise reflecting increased certainty, even when decision choice does not require additional motor accuracy, but this is influenced by individual differences and prior reward. These data uncover the hidden potential for touchscreen tasks in any species to uncover the latent neural states that unite cognition and movement.
Hippocampal subfield volume in relation to cerebrospinal fluid Amyloid-ß in early Alzheimer’s disease: Diagnostic Utility of 7T MRI
Authors: Adeyemi Oluwatobi F , Gowland Penny , Bowtell Richard , Mougin Olivier , Hosseini Akram A.
Published: October 2024

INTRODUCTION

Alzheimer’s disease (AD) is a neurodegenerative condition characterised by amyloid plaque accumulation and neurofibrillary tangles. Early detection is essential for effective intervention, but current diagnostic methods that enable early diagnosis in clinical practice rely on invasive or costly biomarker scanning. This study aimed to explore the utility of 7T MRI in assessing hippocampal subfield volumes and their correlation with cerebrospinal fluid (CSF) biomarkers in prodromal AD. METHODS: Fifty-six participants, including AD patients and healthy controls, underwent 7T MRI scanning. Automated segmentation delineated hippocampal subfield volumes, with subsequent normalization to whole brain volume.

RESULTS

Significant differences in hippocampal and subfield volumes were observed in prodromal AD patients, even when they did not exhibit high MTA scores on 3T MRI or show any whole brain volume loss. Additionally, the volume of the entorhinal cortex (ERC) correlated significantly with CSF amyloid-β levels, suggesting ERC’s potential as a proxy CSF amyloid-ß measurement. Conversely, no significant associations were found between CSF 181-phospho-tau or total tau levels and any hippocampal subfield volumes.

DISCUSSION

These findings show the potential use of 7T MRI, particularly in ERC assessment, as a biomarker for early AD identification. Further validation studies are warranted to confirm these results and elucidate the relationship of ERC volume with CSF biomarkers.
Persistence of training-induced visual improvements after occipital stroke
Authors: Willis Hanna E. , Farenthold Berkeley , Millington-Truby Rebecca S. , Willis Rebecca , Starling Lucy , Cavanaugh Matthew , Tamietto Marco , Huxlin Krystel , Bridge Holly
Published: October 2024

Damage to the primary visual cortex causes homonymous visual impairments that appear to benefit from visual discrimination training. However, whether improvements persist without continued training remains to be determined and was the focus of the present study. After a baseline assessment visit, 20 participants trained twice daily in their blind-field for a minimum of six months (median=155 sessions), using a motion discrimination and integration task. At the end of training, a return study visit was used to assess recovery. Three months later, 14 of the participants returned for a third study visit to assess persistence of recovery. At each study visit, motion discrimination and integration thresholds, Humphrey visual fields, and structural MRI scans were collected. Immediately after training, all but four participants showed improvements in the trained discrimination task, and shrinkage of the perimetrically-defined visual defect. While these gains were sustained in seven out of eleven participants who improved with training, four participants lost their improvement in motion discrimination thresholds at the follow-up visit. Persistence of recovery was not related to age, time since lesion, number of training sessions performed, proportion of V1 damaged, deficit size, or optic tract degeneration measured from structural MRI scans. The present findings underscore the potential of extended visual training to induce long-term improvements in stroke-induced vision loss. However, they also highlight the need for further investigations to better understand the mechanisms driving recovery, its persistence post-training, and especially heterogeneity among participants.
Trends in smoking prevalence and socioeconomic inequalities across regions in England: a population study, 2006 to 2024
Authors: Jackson Sarah E. , Cox Sharon , Buss Vera , Tattan-Birch Harry , Brown Jamie
Published: October 2024

Background

In addition to national policies and interventions, certain regions in England (particularly in the North) coordinate regional tobacco control programmes. This study examined trends in tobacco smoking prevalence and socioeconomic inequalities in smoking across regions.

Methods

Data were obtained from monthly household surveys of adults (≥16y) in England, conducted between November 2006 and July 2024 (totaln=368,057). We used logistic regression to estimate time trends in current smoking by region, and tested interactions with occupational social grade to explore differences between more and less advantaged groups.

Results

Smoking prevalence declined most in the North (28.8% to 15.8%; -12.9 percentage points [95%CI -14.4; -11.5]), similar to the national average in the Midlands (25.2% to 16.0%; -9.2 [-10.6; -7.9]), and least in the South (22.7% to 17.3%; -5.3 [-6.5; -4.0]), reducing regional disparities such that prevalence was similar across regions in 2024. Socioeconomic inequalities in smoking prevalence between more and less advantaged social grades fell most in Yorkshire and the Humber (from 17.9 percentage points [14.1; 21.8] to 3.7 [0.4; 7.0]) and the West Midlands (from 16.1 [12.8; 19.6] to 3.0 [-0.03; 6.0]). Regions with sustained regional tobacco control activity saw greater declines in smoking prevalence (−18.1 [-21.4; - 14.7]) than regions with none (−12.8 [-13.9; -11.6]).

Conclusions

Between 2006 and 2024, smoking rates in the North of England fell faster than the national average, aligning with other regions. Regional tobacco control programmes appeared to contribute to this progress.
Impulsive adolescents exhibit inefficient processing and a low decision threshold when decoding facial expressions of emotions
Authors: Schreiber Alison M. , Hall Nathan T. , Parr Daniel F. , Hallquist Michael N.
Published: October 2024

Background

Borderline personality disorder (BPD) is a debilitating psychiatric illness whose symptoms frequently emerge during adolescence. Initial studies in adults suggest that the interpersonal difficulties common in BPD may emerge from disrupted processing of social and emotional stimuli. Less is known about these processes in adolescents with BPD symptoms, despite substantial changes in socioemotional processing during this developmental period.

Methods

86 adolescents and young adults with and without BPD symptoms completed an emotional interference task involving the identification of a facial emotion expression in the presence of a conflicting or congruent emotion word. We used hierarchical drift diffusion modeling to index speed of processing and decision boundary. Using Bayesian multilevel regression, we characterized age-related differences in facial emotion processing. We then examined whether BPD symptom dimensions were associated with facial emotion processing on this task. To determine the specificity of our effects, we analyzed behavioral data from a corresponding nonemotional interference task.

Results

Impulsivity, but not negative affectivity or interpersonal dysfunction, predicted inefficient processing when presented with conflicting negative emotional stimuli. Across both tasks, impulsivity in adolescents was further associated with a lower decision boundary. Impulsive adolescents were especially likely to make fast, but inaccurate decisions about another person’s emotional state.

Conclusion

Impulsive adolescents with BPD symptoms are prone to making errors when appraising facial expressions of emotions, which may potentiate or worsen interpersonal conflicts. Our findings highlight the role of lower-level social cognitive processes in interpersonal difficulties among vulnerable youth during a sensitive developmental window.
Soft-gluon exchange matters: Isotropic screening in QCD kinetic theory
Authors: Boguslavski K. , Lindenbauer F.
Published: October 2024

QCD kinetic theory simulations are a prominent tool for studying the nonequilibrium initial stages in heavy-ion collisions. Despite their success, all implementations rely on approximations of the hard thermal loop (HTL) screened matrix elements in the collision terms. In this paper, we present our results for different isotropic screening prescriptions in the elastic collision term for gluons. In particular, we go beyond the simple Debye-like screening form that is used in all current implementations and apply the isotropic HTL matrix element instead. For isotropic systems, the evolution is nearly unchanged, but when studying the equilibration process in a Bjorken expanding plasma, we find qualitative and quantitative differences in a range of moments of the distribution function, such as a decrease in the maximum pressure anisotropy by up to 50%. In contrast, we find no significant qualitative impact on the jet quenching parameter or on the late-time hydrodynamization dynamics of anisotropic plasmas, but observe systematically smaller values of η/s by about 10% that coincide with perturbative calculations at small couplings. Our study reveals that the choice of the screening prescription can lead to large corrections at early times, but is less important close to equilibrium.

Published by the American Physical Society
2024
Streamlining latent spaces in machine learning using moment pooling
Authors: Gambhir Rikab , Osathapan Athis , Thaler Jesse
Published: October 2024

Many machine learning applications involve learning a latent representation of data, which is often high-dimensional and difficult to directly interpret. In this work, we propose “moment pooling,” a natural extension of deep sets networks which drastically decreases the latent space dimensionality of these networks while maintaining or even improving performance. Moment pooling generalizes the summation in deep sets to arbitrary multivariate moments, which enables the model to achieve a much higher effective latent dimensionality for a fixed learned latent space dimension. We demonstrate moment pooling on the collider physics task of quark/gluon jet classification by extending energy flow networks (EFNs) to moment EFNs. We find that moment EFNs with latent dimensions as small as 1 perform similarly to ordinary EFNs with higher latent dimension. This small latent dimension allows for the internal representation to be directly visualized and interpreted, which in turn enables the learned internal jet representation to be extracted in closed form.

Published by the American Physical Society
2024
Analysis of
DD*
and
D¯(*)Ξcc(*)
molecule by one boson exchange model based on heavy quark symmetry
Authors: Asanuma Tatsuya , Yamaguchi Yasuhiro , Harada Masayasu
Published: October 2024

Numerous exotic hadrons with heavy quarks have been reported in the experiments. In such states, symmetries of heavy quarks are considered to play a significant role. In particular, the superflavor symmetry, or also called the heavy quark antidiquark symmetry is one of the interesting symmetries, which links a quark Q to an antidiquark Q¯Q¯ having the same color representation as Q. In this paper, we study a D¯Ξcc molecular state as a superflavor partner of the doubly charmed tetraquark

T

c

c

reported by LHCb recently. Tcc locating slightly below the DD* threshold is a candidate of the hadronic molecule. Thus by replacing the singly charmed meson D(*) with the doubly charmed baryon Ξcc(*), superflavor symmetry predicts the existence of the D¯(*)Ξcc(*) bound state. We employ the one boson exchange model respecting with the heavy quark spin symmetry where the parameter is obtained to reproduce the Tcc binding energy. We apply this model with superflavor symmetry to the D¯(*)Ξcc(*) molecule and predict a bound state with I(JP)=0(12−). If the pentaquark state corresponding to D¯(*)Ξcc(*) molecular state is observed in future experiments as predicted in this work, it is more likely that Tcc is a DD* molecular state.

Published by the American Physical Society
2024
Constraints on dark matter from dynamical heating of stars in ultrafaint dwarfs. II. Substructure and the primordial power spectrum
Authors: Graham Peter W. , Ramani Harikrishnan
Published: October 2024

There is a large and growing interest in observations of small-scale structure in dark matter. We propose a new way to probe dark matter structures in the ∼10–108M⊙ range. This allows us to constrain the primordial power spectrum over shorter distances scales than possible with direct observations from the CMB. For k in the range ∼10–1000  Mpc−1 our constraints on the power spectrum are orders of magnitude stronger than previous bounds. We also set some of the strongest constraints on dark matter isocurvature perturbations. Our method relies on the heating effect such dark matter substructures would have on the distribution of stars in an ultrafaint dwarf galaxy. Many models of inflation produce enhanced power at these short distance scales and can thus be constrained by our observation. Further, many dark matter models such as axion dark matter, self-interacting dark matter and dissipative dark matter, produce dense structures which could be constrained this way.

Published by the American Physical Society
2024
Theoretical constraints on models with vectorlike fermions
Authors: Adhikary Amit , Olechowski Marek , Rosiek Janusz , Ryczkowski Michał
Published: October 2024

We provide a set of theoretical constraints on models in which the Standard Model field content is extended by vectorlike fermions and in some cases also by a real scalar singlet. Our approach is based on the study of electroweak vacuum stability, perturbativity of model couplings, and gauge couplings unification with the use of renormalization group equations. We show that careful analysis of these issues leads to strong constraints on the parameter space of the considered models. This, in turn, has important implications for phenomenology, as we show using examples of the double Higgs boson production, electroweak precision observables, and the electroweak phase transition.

Published by the American Physical Society
2024