bluuebunny/crossref_metadata_2025 huggingface dataset:
Depressive symptoms and physical activity mediate the adverse effect of pain on functional independence in patients with arthritis: Evidence from the Canadian Longitudinal Study on Aging
Authors: Goubran Miriam , van Allen Zachary M. , Bilodeau Martin , Boisgontier Matthieu P.
Published: February 2025

Objective

Arthritis is a chronic condition affecting hundreds of millions of people worldwide, often leading to pain and functional limitations. This study aimed to investigate the direct and indirect effects of pain on functional independence in individuals with arthritis. Depressive symptoms and physical activity were examined as potential mediators of this relationship.

Methods

A total of 6972 participants with arthritis (4930 with osteoarthritis and 694 with rheumatoid arthritis) were included from the Canadian Longitudinal Study on Aging. Multiple linear regression models, generalized linear models, and bootstrapping were used to assess the relationships between baseline pain, depressive symptoms, physical activity, and functional status at follow-up.

Results

Baseline pain was positively associated with depressive symptoms (b = 0.356 [95% CI: 0.310 to 0.402]) and negatively associated with physical activity (b = −0.083 [95% CI: −0.125 to −0.042]). Functional status at follow-up was significantly predicted by baseline pain (OR = 1.834 [95% CI: 1.306 to 2.610]), depressive symptoms (OR = 1.431 [95% CI: 1.205 to 1.709]), and physical activity (OR = 0.550 [95% CI: 0.440 to 0.683]). Mediation analysis showed that 30.4% of the effect of pain on functional status was mediated by the total indirect effect, with contributions from depressive symptoms (19.8%), physical activity (8.9%), and the serial mediation pathway (1.7%).

Conclusions

Pain at baseline was associated with a higher likelihood of functional dependence in basic and instrumental activities of daily living after a mean follow-up period of 6.3 years, with depressive symptoms and lower physical activity acting as partial mediators. These findings highlight the importance of managing pain, mental health, and physical activity in patients with arthritis to maintain functional independence.

Impact

These findings support the importance for intervention to target both mental health and exercise to mitigate functional decline resulting from the long-term effects of pain in patients with arthritis.
Hemispherotomy: a cortical island of sleep-like activity in awake humans
Authors: Colombo Michele A. , Favaro Jacopo , Mikulan Ezequiel , Pigorini Andrea , Zauli Flavia M. , Sartori Ivana , d’Orio Piergiorgio , Castana Laura , Toldo Irene , Sartori Stefano , Sarasso Simone , Bayne Tim , Seth Anil K. , Massimini Marcello
Published: February 2025

Hemispherotomy is a neurosurgical procedure for treating refractory epilepsy, which entails disconnecting a significant portion of the cortex, potentially encompassing an entire hemisphere, from its cortical and subcortical connections. While this intervention prevents the spread of seizures, it raises important questions. Given the complete isolation from sensory-motor pathways, it remains unclear whether the disconnected cortex retains any form of inaccessible awareness. More broadly, the activity patterns that large portions of the deafferented cortex can sustain in awake humans remain poorly understood.

We address these questions by exploring for the first time the electrophysiological state of the isolated cortex before and after surgery in ten awake pediatric patients. Post-surgery, the isolated cortex exhibited prominent slow oscillations (<2 Hz) and a broad-band shift in power spectral density from high to low frequencies. This resulted in a marked decrease of the spectral exponent, a validated consciousness marker, indicating broad-band slowing characteristic of unconscious states.

When compared with a reference pediatric sample across the sleep-wake cycle, the spectral exponent of the contralateral cortex aligned with wakefulness, whereas that of the isolated cortex was consistent with deep NREM sleep. However, spindles did not emerge in the isolated cortex due to the lack of subcortical inputs, constituting a fundamental difference from physiological sleep.

These findings demonstrate a unihemispheric sleep-like state during wakefulness, challenging the possibility that hemispherotomy might lead to inaccessible “islands of awareness.” Moreover, the persistence of sleep-like patterns years after disconnection provides unique insights into the electrophysiological effects of disconnections in the human brain.
Investigating the Role ofOnchocerca ochengiin Epilepsy Development: A Gerbil Model Study
Authors: Ayiseh Rene Bilingwe , Anangafack Fobang Ulrick , Etaka Judith Christine , Dobgima Gamua Stanley , Bimela Chrysantus Njobinkir , Ghogomu Stephen Mbigha , Cho-Ngwa Fidelis
Published: February 2025

Background

Onchocerca volvulusinfection is linked to onchocerciasis-associated epilepsy (OAE) in humans, but the role ofOnchocerca ochengiin epilepsy development remains unexplored. This study aimed to investigate whetherO. ochengiinfection contributes to epilepsy development.

Methodology/Principal Findings

Gerbils were implanted withO. ochengiworm masses (test group) or underwent sham surgery (control group). Behavioral and physical assessments were performed between days 15–19 using multiple tests, including the elevated plus maze, open-field, object recognition, and hanging wire tests. On day 21, gerbils were sacrificed, and body/organ weights were recorded, along with worm mass survival. Implantation of 15 worm masses resulted in 100% mortality in the test group, while implantation of 10 worm masses resulted in 53.3% mortality, with all control animals surviving. At day 21, worm mass survival averaged 1.4 out of 10, with a viability score of 93.3%. Test animals showed significant reductions in body weight and increased spleen weight compared to controls, but no significant behavioral differences were observed.

Conclusions/Significance

WhileO. ochengiinfection caused notable physical effects, including high mortality and changes in body/organ weights, no behavioral evidence of epilepsy was observed. The high mortality rate and limited observation period restrict the interpretation of these findings. Further studies with larger cohorts and longer observation periods are needed to assess the potential role ofOnchocerca spp. in epilepsy development. To the best of our knowledge, this study represents the first attempt to establish an animal model for OAE.

Author Summary

Onchocerca volvulusinfection is linked to onchocerciasis-associated epilepsy (OAE) in humans, but we know less about whether other types ofOnchocerca, such asOnchocerca ochengi, might also contribute to epilepsy. Our study aimed to investigate this question by infecting gerbils withO. ochengiworm masses and observing the impact on their behavior and physical health. We found that while the infection caused significant physical changes, including high mortality rates and changes in body and organ weights, there were no signs of behavioral changes typical of epilepsy. In particular, we did not see any of the usual neurological symptoms that might indicate epilepsy. These results suggest that whileO. ochengican affect animal health in some ways, it might not be directly involved in causing epilepsy. However, the high mortality rate in the infected gerbils and the relatively short duration of the study mean that we cannot draw firm conclusions. Future research with more animals and a longer time frame will be important to better understand whetherOnchocercaworms contribute to epilepsy development in humans.
High-Fidelity Long-Read Sequencing of an Avian Herpesvirus Reveals Extensive Intrapopulation Diversity in Tandem Repeat Regions
Authors: Ortigas-Vasquez Alejandro , Bowen Christopher D , Renner Daniel W , Baigent Susan J , Zhang Yaoyao , Yao Yongxiu , Nair Venugopal , Kennedy David A , Szpara Moriah L
Published: February 2025

Comparative genomic studies of Marek's disease virus (MDV) have suggested that attenuated and virulent strains share >98% sequence identity. However, these estimates fail to account for variation in regions of the MDV genome harboring tandem repeats. To resolve these loci and enable assessments of intrapopulation diversity, we used a PacBio Sequel II platform to sequence MDV strains CVI988/Rispens (attenuated), HPRS-B14 (virulent), Md5 (very virulent) and 675A (very virulent plus). This approach enabled us to identify patterns of variation in tandem repeat regions that are consistent with known phenotypic differences across these strains. We also found CVI988/Rispens variants showing a 4.3-kb deletion in the Unique Short (US) region, resulting in the loss of five genes. These findings support a potential link between MDV tandem repeats and phenotypic traits like virulence and attenuation, and demonstrate that DNA viruses can harbor high levels of intrapopulation diversity in tandem repeat regions.
Cethromycin Pharmacokinetics and Pharmacodynamics for Single Dose Cure ofPlasmodium bergheiLiver Stages
Authors: Kennedy Grace J , West Rachel M. , Poti Kristin , Bobb Bryce , Ippolito Matthew Michael , Marzinke Mark A , Kaludov Nikola , Sullivan David J
Published: February 2025

Cethromycin combines a quinoline nucleus and a macrolide for broad spectrum antibacterial and antiprotozoan activity. Here we characterized the murine pharmacokinetics andPlasmodium bergheilifecycle stage pharmacodynamics for the cethromycin base. Liver pharmacokinetic studies in mice show peak mM drug levels in the liver with 20 hour sustained levels above 10 mM. Peak concentrations in the liver were double the lung and about 440 times that of plasma. Immunofluorescence imaging ofin vitrocethromycin-treated infected hepatocytes shows complete ablation of the apicoplast. We observed complete cure ofP. bergheiliver stage infection by single oral dose of 60 mg/kg in mice which is equivalent to the 5 mg/kg human dose of 300 mg a day used in bacterial pneumonia studies. Cethromycin at 60 mg/kg daily for 7 days was curative in the high parasitemicP. bergheimouse model. Both mosquito membrane feeding ofP. falciparumgametocytes incubated with 20 mM cethromycin and oral dosing in mice demonstrated no decrease in oocyst numbers. Cethromycin has been evaluated for efficacy against bacterial pneumonia in more than 5,000 patients with good safety profiles. Cethromycin has potential for rapid clinical development for casual malaria prophylaxis and possibly radical cure of dormant liverP. vivax.
Semiparametric Confidence Sets for Arbitrary Effect Sizes in Longitudinal Neuroimaging
Authors: Zhang Xinyu , Liao Kenneth , Seidlitz Jakob , McHugo Maureen , Avery Suzanne N. , Huang Anna , Alexander-Bloch Aaron , Woodward Neil , Heckers Stephan , Vandekar Simon
Published: February 2025

The majority of neuroimaging inference focuses on hypothesis testing rather than effect estimation. With concerns about replicability, there is growing interest in reporting standardized effect sizes from neuroimaging group-level analyses. Confidence sets are a recently developed approach to perform inference for effect sizes in neuroimaging but are restricted to univariate effect sizes and cross-sectional data. Thus, existing methods exclude increasingly common multigroup or nonlinear longitudinal associations of biological brain measurements with inter- and intra-individual variations in diagnosis, development, or symptoms. We broadly generalize the confidence set approach by developing a method for arbitrary effect sizes in longitudinal studies. Our method involves robust estimation of the effect size image and spatial and temporal covariance function based on generalized estimating equations. We obtain more efficient effect size estimates by concurrently estimating the exchangeable working covariance and using a nonparametric bootstrap to determine the joint distribution of effect size across voxels used to construct confidence sets. These confidence sets identify regions of the image where the lower or upper simultaneous confidence interval is above or below a given threshold with high probability. We evaluate the coverage and simultaneous confidence interval width of the proposed procedures using realistic simulations and perform longitudinal analyses of aging and diagnostic differences of cortical thickness in Alzheimer’s disease and diagnostic differences of resting-state hippocampal activity in psychosis. This comprehensive approach along with the visualization functions integrated into the pbj R package offers a robust tool for analyzing repeated neuroimaging measurements.
Too little and too much: medial prefrontal functional inhibition impairs early acquisition of operant reversal learning, whereas medial prefrontal disinhibition impairs established serial-reversal performance in rats
Authors: Renström Jacco G. , Taylor Charlotte J.L , Grasmeder Allen Rachel , Loayza Joanna , O’Hara Luke , von Heimendahl Moritz , Deiana Serena , Moran Paula M. , Stevenson Carl W. , Maggi Silvia , Bast Tobias
Published: February 2025

Schizophrenia has been linked to hypofrontality (reduced prefrontal activation) and neural disinhibition (reduced GABAergic inhibition) within the dorsolateral prefrontal cortex (dlPFC), as well as reversal learning deficits. Interestingly, whilst reversal learning has been strongly linked to the orbitofrontal cortex, research suggests that the primate dlPFC – or its rodent analogue, the medial PFC (mPFC) – is less important for this process. Nevertheless, we hypothesized that the mPFC may be required for reversal learning if the reversal is particularly demanding. Furthermore, even if the mPFC is not required, mPFC disinhibition may impair reversals, because it may disrupt processing in mPFC projection sites. To test this, we induced mPFC functional inhibition and disinhibition in rats, using microinfusions of the GABA-A receptor agonist muscimol or antagonist picrotoxin, respectively, and examined the impact on early and serial reversals on a food-reinforced two-lever discrimination task. Using classical performance measures and Bayesian trial-by-trial strategy analysis, we found that mPFC functional inhibition impaired early, but not serial, reversals by increasing perseveration and impairing exploratory (lose-shift) behavior. In contrast, disinhibition impaired serial reversals, which was associated with reduction in both exploratory (lose-shift) and exploitative (win-stay) behavior. These findings suggest that mPFC hypoactivation and disinhibition disrupt distinct aspects of reversal learning by different mechanisms.
The role of symmetry breaking in connectivity and neurodegeneracy in the brain’s resting state dynamics
Authors: Gudibanda Kashyap , Fousek Jan , Petkoski Spase , Jirsa Viktor
Published: February 2025

The functioning of brain networks can be broadly categorized as an interplay of two main contributors, namely the neurological processes dictating the local dynamics and the patterns of anatomical connections that enable the interactions between the various local processes, resulting in a global emergent behavior. Using Brain Network Modeling we describe the constraints of the anatomical structure upon the resting state dynamics of the human brain. We identify a low-dimensional representation of the brain states, the Resting State Manifold (RSM), and leveraging network degeneracy and its relationship to structural properties, we identify dynamic patterns supported by the RSM. Noise driven dynamics of the BNM are used to explore the manifold and validate the contours of degeneracy. We demonstrate that the patterns of degeneracy regulate the dynamics of the broader system in the presence of external and/or internal perturbations, revealing the productive relationship between emergent network processes and their constituent network entities.
Fast adaptation in invertebrate looming-sensitive descending neurons
Authors: Sporar Klinge Katja , Nordström Karin
Published: February 2025

Motion vision plays a crucial role in guiding dynamic behaviors, such as determining when to escape from predators, pursue prey, navigate obstacles, or adjust flight patterns during migration. Adaptation to repetitive motion stimuli is a crucial aspect of this process, allowing animals to efficiently process new stimuli while avoiding sensory overload. This helps animals remain responsive to novel or important stimuli, ensuring appropriate behavioral reactions. Adaptation to looming stimuli, which often signal an approaching threat through the rapid expansion of an object’s image on the retina, allows animals to distinguish harmless from harmful stimuli. While neural adaptation has been extensively studied in the fly’s optic lobes, less is known about how descending neurons, which link the optic lobes to the motor centers in the thoracic ganglia, adapt. To address this gap, we investigate adaptation in looming-sensitive descending neurons in the hoverflyEristalis tenax. Using intracellular recordings, we show that these descending neurons adapt to looming stimuli with inter-stimulus intervals of 1-3 s. We show that the level of adaptation depends on the ISI, with shorter intervals leading to greater adaptation. Specifically, we find that adaptation leads to decreased response duration, with a pronounced delayed response onset. We identified descending neurons that responded to looming stimuli either unilaterally or bilaterally and used this to show that most of the adaptation takes place within the neuron itself, rather than its pre-synaptic inputs. Finally, we found that the wing beat amplitude of tethered hoverflies did not appear to adapt to repetitive looming stimuli.

Significance Statement

Rapidly expanding looming objects often signal approaching threats, and appropriate detection is therefore critical for survival across species. Adaptation to repetitive looming cues allows animals to filter out irrelevant information, ensuring they respond only to significant threats. While adaptation has been well studied in the brain, how descending neurons, which connect the brain with the body, adapt to looming stimuli remains poorly understood. Here, we investigate looming-sensitive descending neurons in the hoverflyEristalis tenaxand show that they adapt strongly when looming stimuli are repeated in quick succession. We show that most of the adaptation takes place within the descending neuron itself. Our research establishes a foundation for future exploration of the neural mechanisms underlying behavior in constantly changing environments.
Methanogenesis marker 16 metalloprotein is the primary coenzyme M synthase inMethanosarcina acetivorans
Authors: Chadwick Grayson L. , Williams Madison C. , Shalvarjian Katie E. , Nayak Dipti D.
Published: February 2025

2-mercaptoethanesulfonate (Coenzyme M, CoM) is an organic sulfur-containing cofactor used for hydrocarbon metabolism in Archaea and Bacteria. In Archaea, CoM serves as an alkyl group carrier for enzymes belonging to the alkyl-CoM reductase family, including methyl-CoM reductase, which catalyzes methane formation in methanogens. Two pathways for the biosynthesis of CoM are present in methanogenic archaea. The initial steps of these pathways are distinct but the last two reactions, leading up to CoM formation, are universally conserved. The final step is proposed to be mediated by methanogenesis marker metalloprotein 16 (MMP16), a putative sulfurtransferase, that replaces the aldehyde group of sulfoacetaldehyde with a thiol to generate CoM. The assignment of MMP16 as CoM synthase (ComF) is not widely accepted as deletion mutants have been shown to grow without any CoM dependence. Here, we investigate the role of MMP16 in the model methanogen,Methanosarcina acetivorans.We show that a mutant lacking MMP16 has a CoM-dependent growth phenotype and a global transcriptomic profile reflective of CoM-starvation. Additionally, the ΔMMP16 mutant is a CoM auxotroph in sulfide-free medium. These data reinforce prior claims that MMP16 is abona fideComF but point to backup pathway(s) that can conditionally compensate for its absence. We found that L- aspartate semialdehyde sulfurtransferase (L-ASST), catalyzing a sulfurtransferase reaction during homocysteine biosynthesis in methanogens, is potentially involved in genetic compensation of the MMP16 deletion. Even though, both, L-ASST and MMP16 are members of the COG1900 family, site-directed mutagenesis of conserved cysteine residues implicated in catalysis reveal that the underlying reaction mechanisms may be distinct. Altogether, we have provided concrete evidence that MMP16 is the primary ComF in methanogenic archaea.

Author Summary

Methane is a high energy renewable fuel that is the primary constituent of natural gas and a potent greenhouse gas. A significant fraction of global methane emissions is generated by the activity of methanogenic archaea. These microorganisms use a cofactor called Coenzyme M (CoM) as a methyl carrier for methane production mediated by the enzyme Methyl-Coenzyme M reductase. Since methane production is essential for energy conservation in methanogens, they need to synthesize or import CoM. Accordingly, most methanogens encode either one of two CoM biosynthesis pathways. Methanogenesis marker 16 metalloprotein (MMP16) is proposed to catalyze the last step of CoM biosynthesis in both pathways however experimental evidence to this effect is lacking. Here we demonstrate that MMP16 is, indeed, the primary CoM synthase (ComF) in the model methanogen,Methanosarcina acetivorans.Since MMP16 is uniquely and widely distributed in methanogens, it can serve as an ideal candidate for the design of anti- methanogenic chemical inhibitors.
Unraveling the mechanism of 1-deoxynojirimycin (DNJ) accumulation: the role of SWEET3 in mulberry chloroplasts
Authors: Yang Zhen , Zhao Shuo , Li Yan , Wei Yeling , Wang Zhonghao , Xia Xiaoyu , Li Dong , He Ningjia
Published: February 2025

Transporters are crucial for the accumulation and secretion of plant metabolic products. 1-Deoxynojirimycin (DNJ), a natural compound widely distributed in nature and known for its medicinal properties, has production limitations in microorganisms and herbaceous plants. Mulberry leaves, being easy to harvest and growing rapidly, are the main source of DNJ. However, the current production from mulberry is insufficient to meet the demand. Improving DNJ content in mulberry and thereby reducing production costs is a significant challenge. We first used a green fluorescent tag to visualize the localization of DNJ and found that DNJ highly accumulates in the chloroplasts of mulberry leaves but not in callus tissue. The sugar transporter gene SWEET3, which is highly expressed in mulberry leaves but not in callus, was shown to have DNJ transport capability. Molecular docking analysis revealed that the acidic amino acid residues E68 and D126 in the SWEET3 protein are potential binding sites for DNJ, and both neutral and basic mutations at these sites significantly reduced the ability to DNJ-transporting ability of SWEET3. Furthermore, transient overexpression or RNA interference of SWEET3 in mulberry leaves significantly increased or decreased DNJ content, respectively. Similarly, stable overexpression of the SWEET3 in mulberry hairy roots led to an enhancement in DNJ content within the roots. Our results demonstrated that SWEET3 is essential for DNJ accumulation in mulberry. The study represents a breakthrough in increasing DNJ yield in mulberry through the key role of transporters and identify specific molecular targets required for developing mulberry germplasm with increased DNJ levels.
Vitamin D deficiency and depressive episodes in adolescents and young adults: systematic review and meta-analysis
Authors: Nano Joseph P. , Catterall William A. , Filer Violet , Khaleghzadegan Salar , Almazan Ricardo , Blunt Heather B. , Yen Renata W.
Published: February 2025

Background

We conducted a systematic review and meta-analysis to examine the relationship between vitamin-D deficiency and depression in adolescents and young adults.

Methods

We searched academic databases and reference lists from inception to July 2023, limited to English studies. We extracted data and assessed study quality using the Newcastle-Ottawa Quality-Assessment-Scale of Cohort Studies. We used random-effects meta-analyses to determine vitamin-D serum levels in depressed vs. non-depressed participants (mean difference) and odds ratio for vitamin-D categories (insufficiency and deficiency) and for gender and age subgroup analyses. We assessed statistical heterogeneity using I2.

Results

From 9,369 citations, we included seventeen studies (2010-2023). Mean sample size was 32,844 (range: 51 to 483,683). Meta-analysis of six studies showed that depressed individuals had lower vitamin-D levels than non-depressed individuals, mean difference = -7.99 nmol/L (95%CI: -14.44 to -1.55; p=0.02; I²=79%). Among the 11 studies not in the meta-analysis, ten found that vitamin-D insufficiency (50-75 nmol/L) and deficiency (<50 nmol/L) were significantly associated with depression. This association was stronger among female participants (OR=1.39, 95%CI: 1.33 to 1.45, I2=88%) and young adults (OR=1.25, 95%CI: 1.18 to 1.33, p<0.001, I2=94%).

Limitations

Our included studies ranged in sample size, which may influence the interpretation and generalizability of the results.

Conclusions

Over half of the studies indicated that vitamin-D insufficiency and deficiency are significantly associated with depression, with important variations by gender and age.
The Relationship Between Visual Motion Detection Thresholds and Visual Sensitivity to Medial/Lateral Balance Control
Authors: DiBianca Stephen J. , Reimann Hendrik , Gray Julia , Peterka Robert J. , Jeka John J.
Published: February 2025

The ability to differentiate between self-motion and motion in the environment is an important factor for maintaining upright balance control. Visual motion can elicit the sensation of a fall by cueing a false position sense. While there is evidence supporting the role of central vision and fall risk, including measures of contrast sensitivity, depth perception, and size of the visual field, the relationship between motion detection thresholds and balance control remains unknown. The aim of this study is to explore the relationship between thresholds for visual motion detection (VMDTs) of the environment and measures of visual sensitivity to balance disturbances in the environment while walking. Thirty young adults (18–35 years) and thirty older adults (55–79 years) participated in a counter-balanced study where they 1) walked on a self-paced treadmill within a virtual environment that delivered frontal plane multi-sine visual disturbances at three amplitudes (6°, 10°, and 15°), and 2) performed 100 trials of a two-alternative forced choice (2AFC) task in which they discriminated between a counterclockwise (“left”) and clockwise (“right”) rotation of a visual scene under three conditions (standing, standing with optic flow, and walking). Visual sensitivity was measured using frequency response functions of the center of mass displacement relative to the screen tilt (cm/deg) while VMDTs were measured by fitting a psychometric curve to the responses of the 2AFC task. We found significant positive correlations between measures of visual sensitivity and VMDTs for 7 out of the 9 conditions in young adults, and nonsignificant positive correlations between the two measures in older adults. VMDTs were overall higher in older adults, although not significantly in the standing condition, indicating more motion in the environment is required for older adults to consciously perceive it. VMDTs also tended to increase from standing, standing with optic flow, and walking, although not significantly between the standing and standing with optic flow conditions for both populations. We interpret the positive correlations between the two measures as an indication that individuals with lower motion detection thresholds can more accurately differentiate between self-motion and motion in the environment, resulting in lower responses from visual disturbances in the environment.
Short 5’ UTRs serve as a marker for viral mRNA translation inhibition by the IFIT2-IFIT3 antiviral complex
Authors: Glasner Dustin R. , Todd Candace , Cook Brian , D’Urso Agustina , Khosla Shivani , Estrada Elena , Wagner Jaxon D. , Bartels Mason D. , Ford Pierce , Prych Jordan , Hatch Katie , Yee Brian A. , Ego Kaori M. , Liang Qishan , Holland Sarah R. , Case James Brett , Corbett Kevin D. , Diamond Michael S. , Yeo Gene W. , Herzik Mark A. , Van Nostrand Eric L. , Daugherty Matthew D.
Published: February 2025

Recognition of “non-self” nucleic acids, including cytoplasmic dsDNA, dsRNA, or mRNAs lacking proper 5’ cap structures, is critical for the innate immune response to viruses. Here, we demonstrate that short 5’ untranslated regions (UTRs), a characteristic of many viral mRNAs, can also serve as a molecular pattern for innate immune recognition via the interferon-induced proteins IFIT2 and IFIT3. The IFIT2-IFIT3 heterodimer, formed through an intricate domain swap structure resolved by cryo-EM, mediates viral mRNA 5’ end recognition, translation inhibition, and ultimately antiviral activity. Critically, 5’ UTR lengths <50 nucleotides are necessary and sufficient to sensitize an mRNA to translation inhibition by the IFIT2-IFIT3 complex. Accordingly, diverse viruses whose mRNAs contain short 5’ UTRs, such as vesicular stomatitis virus and parainfluenza virus 3, are sensitive to IFIT2-IFIT3-mediated antiviral activity. Our work thus reveals a pattern of antiviral nucleic acid immune recognition that takes advantage of the inherent constraints on viral genome size.
Mapping Anhedonia-Related Damage Network: Insights for TMS Treatment
Authors: Chen Chengfeng , Wang Shiying , Liu Yuan , Zhang Xuezhen , Rong Xinyan , Wang Jiang , Wang Jijun , Sun Ling , Zhang Bin
Published: February 2025

Background

Many studies have explored anhedonia-related functional connectivity (FC), but the findings remain inconsistent. There is a gap in identifying a consistent anhedonia-related damage network and applying it to TMS treatment.

Methods

We systematically reviewed studies on anhedonia-related functional connectivity and identified anhedonia-related brain damage locations. Using a novel functional connectivity network mapping approach applied to a large normative connectome dataset, we mapped these damage locations to anhedonia-related damage networks. Subsequently, transcriptomic analysis was conducted to uncover underlying molecular mechanisms. Additionally, we investigated the application of the anhedonia-related damage network in transcranial magnetic stimulation (TMS) treatment, focusing on changes in FC within this network following TMS treatment and its association with anhedonia improvement, as well as predicting TMS treatment efficacy based on baseline FC within the anhedonia-related damage network.

Results

A total of eight experiments from seven studies using the nucleus accumbens (NAc) as the seed were eligible for functional connectivity network mapping analysis. This study identified an anhedonia-related damage network, primarily characterized by disrupted functional connectivity between the NAc and the default mode network. Transcriptomic analysis revealed gene enrichment associated with synaptic signaling, neuronal development, ion transport, and actin cytoskeleton regulation. TMS treatment increased NAc functional connectivity within the anhedonia-related damage network in the response group, with these changes correlating with improvements in anhedonia. Furthermore, baseline NAc FC within this network demonstrated predictive potential for TMS treatment efficacy.

Conclusion

The anhedonia-related damage network was identified, emphasizing its underlying mechanisms and predictive value for TMS in treating anhedonia.
Elimination of separase inhibition reveals absence of cohesin protection in oocyte metaphase II
Authors: Jailani Safia El , Cladière Damien , Nikalayevich Elvira , Touati Sandra A. , Chesnokova Vera , Melmed Shlomo , Buffin Eulalie , Wassmann Katja
Published: February 2025

The meiotic segregation pattern to generate haploid gametes is mediated by step-wise cohesion removal by separase, first from chromosome arms in meiosis I, and then from the centromere region in meiosis II. In mammalian oocytes, separase is tightly controlled during the hours-long prometaphase and until chromosome segregation in meiosis I, activated for a short time window, and again inhibited until metaphase II arrest is lifted by fertilization. Centromeric cohesin is protected from cleavage by Sgo2-PP2A in meiosis I. It remained enigmatic how tight control of alternating separase activation and inactivation is achieved during the two divisions in oocytes. It was equally unknown when cohesin protection is put in place and removed. Using structure-function assays in knock-out mouse models we established the contributions of cyclin B1 and securin for separase inhibition during both divisions. When eliminating separase inhibition we found that cohesin is not protected early in meiosis I and at metaphase II arrest. Importantly, in meiosis II, the sole event required for cleavage of centromeric cohesin besides separase activation is prior kinetochore individualization in meiosis I.
Centrosome-assisted assembly of the Balbiani body
Authors:   Divyanshi, Li Meining , Böke Elvan , Yang Jing
Published: February 2025

The Balbiani body (Bb), which was discovered about 170 years ago, is a membraneless organelle in the oocyte in most species. In organisms likeXenopusand Zebrafish, Bb accumulates mitochondria, endoplasmic reticulum (ER), and germline determinants and regulates the proper localization of germline determinants. The Bb forms around the centrosome in the oocyte during early oogenesis. The mechanism behind its assembly has gained attention only very recently. Here, we report that overexpression of the germ plasm matrix protein Xvelo leads to the formation of a ‘Bb-like’ structure in somatic cells. The ‘Bb-like’ structure assembles around the centrosome and selectively recruits mitochondria, ER, and germline determinants. Taking advantage of this system, we investigated the roles of centrosome components on the assembly of Xvelo. Our results reveal that multiple components of the centrosome, including Sas6, Cenexin, and DZIP1, interact with Xvelo and promote its assembly, with Sas6 exhibiting the most prominent activity. Importantly, knocking down Sas6, Cenexin, and DZIP1 individually or in combination resulted in reduced Xvelo aggregates. Taken together, our work suggests that the centrosome may function as a nucleation center to promote the initiation of Xvelo assembly, resulting in the formation of the Bb around the centrosome.
Incorporation of complex narratives into dreaming
Authors: Palmieri Jessica , Kumral Deniz , Wymer Sammy-Jo , Kirchner Susanne , Schneider Maximilian , Gais Steffen , Schönauer Monika
Published: February 2025

Reactivation of waking neuronal activity during sleep holds a functional role in memory consolidation. Reprocessing of daytime memory in dreams might aid later memory performance in a similar way. Numerous findings hint at a link between dreaming and sleep-dependent memory processing, however, studies investigating day-residue incorporation in dreaming led to mixed results so far. In this study, we used a naturalistic learning paradigm aimed at biasing dream content by manipulating pre-sleep experience. Participants listened to one of four different audiobooks while falling asleep and were awoken several times during the night to report their dreams. Afterwards, we tested how well they remembered the content of the audiobook. We then asked three blind raters to guess, based solely on anonymized dream reports, which audiobook someone had listened to before experiencing a dream. Our findings show that dreams across the whole night and from both NREM and REM awakenings contain specific information about the content of narratives studied before sleep. Moreover, if participants dreamt of the audiobook, they retained the content better across the sleep period. Finally, memory performance was lower when the experimental situation was incorporated into dreams, regardless of the presence of audiobook content, suggesting competitive reprocessing between audiobook and experimental memory representations.
Retro Nasal blockade reduces the Neural Processing of Sucrose in the Human Brain
Authors: Ko Hee-kyoung , Shi Jingang , Eidenberger Thomas , Shi Weiyao , McCabe Ciara
Published: February 2025

Traditionally, taste perception is understood to occur through taste receptors located in the oral cavity, particularly on the tongue. Recent findings suggest that taste compounds, when aerosolized, can reach the retro nasal olfactory region and be perceived. However, the neural mechanisms by which the human brain interprets taste stimuli via retro nasal pathways remain unclear.

Healthy adults (N=34, Mean age 25 yrs.) were recruited. We examined neural activity during the tasting of sucrose with a nose clip on (to block retro nasal sensation) compared to when there was no nose clip. We examined whole brain data and ROIs involved in taste (insula, postcentral gyrus, amygdala), smell (olfactory cortex, piriform cortex) odour attention (sgACC) and multi-modal flavour processing (OFC) and reward (pgACC and nucleus accumbens). We also examined subjective ratings of pleasantness and fullness of the sucrose with and without the nose clip.

We found that the nose clip condition reduced neural activity in primary taste and olfaction regions and regions involved in attention to odours, and food reward. When examining the whole brain activity, we also found reduced activity in the rolandic operculum, lingual gyrus and precuneus. The olfactory cortex and prefrontal cortex ROIs tracked the sucrose subjective fullness ratings, but this effect was not present with the nose clip on.

In conclusion, our findings are the first to demonstrate that blocking retro nasal sensation with a nose clip significantly reduces the subjective and objective neural responses to sucrose taste. These findings support the idea that retro nasal sensations could play a role in the perception of sucrose taste. This study suggests that developing more satisfying low-sugar foods could be achieved by enhancing the perception of sweetness through aroma modulation.
Mechanism of Nanomaterial-Induced Lipid Droplet Formation inRaphidocelis subcapitatais Mediated by Charge Properties
Authors: McKeel Emma , Kim Hye-In , Jeon Su-ji , McKinnon Britta , Giraldo Juan Pablo , Klaper Rebecca
Published: February 2025

Increasing the production of renewable energy will be critical to achieving global sustainability goals in the coming decades. Biofuels derived from microalgae have great potential to contribute to this production. However, cultivating algae with sufficient neutral lipid content, while maintaining high growth rates, is a continual challenge in making algal-derived biofuels a reality. Previous work has shown that exposure to polymer-functionalized carbon dots can increase the lipid content of the microalgaeRaphidocelis subcapitata. This study investigates this finding, aiming to determine the mechanisms underlying this effect and if altering nanoparticle surface charge mediates the mechanism of action of the carbon dots used. Carbon dots with both negative and positive surface charges were added to microalgal cultures, and the impacts of this exposure were analyzed using high-content imaging, growth measurements, and chlorophyll content measurements. Results indicate that positively charged carbon dots induce a nano-specific increase in lipid content but also cause decreases in growth. Additionally, the mechanism of action of each nanoparticle was examined by conducting a morphological comparison to known treatments. This analysis showed that negatively charged carbon dots cause similar impacts toR. subcapitataas nitrogen deprivation, a known mechanism by which lipid droplet content can be increased. The findings of this study suggest that carbon dots may have surface charge dependent effects on the lipid metabolism ofR. subcapitata. Future work should consider the use of carbon dots with varied surface charge densities for enhancing algae biofuel production in bioreactors.
High-throughput Single-Virion DNA-PAINT Reveals Structural Diversity, Cooperativity and Flexibility during Selective Packaging in Influenza
Authors: Hepp Christof , Zhao Qing , Robb Nicole , Fodor Ervin , Kapanidis Achillefs N.
Published: February 2025

Influenza A, a negative-sense RNA virus, has a genome that consists of eight single-stranded RNA segments. Influenza co-infections can result in re-assortant viruses that contain gene segments from multiple strains, causing pandemic outbreaks with severe consequences for human health. The outcome of re-assortment is likely influenced by a selective sequence-specific genome packaging mechanism.

To uncover the contributions of individual segment pairings to selective packaging, we set out to statistically analyse packaging defects and inter-segment distances in individual A/Puerto Rico/8/34 (H1N1) (PR8) virus particles. To enable such analysis, we developed a multiplexed DNA-PAINT approach capable of assessing the segment stoichiometry of more than 10,000 individual virus particles in one experiment; our approach can also spatially resolve the individual segments inside complete virus particles with a localisation precision of ~10 nm.

Our results show the influenza genome can be assembled through multiple pathways in a redundant and cooperative process guided by preferentially interacting segment pairs and aided by synergistic effects that enhance genome assembly, driving it to completion. Our structural evidence indicates that the interaction strength of segment pairs affects the spatial configuration of the gene segments, which appears to be preserved in mature virions. As our method quantified the interactions of whole influenza segments instead of identifying individual sequence-based interactions, our results can serve as a template to quantify the contributions of individual sequence motifs to selective packaging.
Data-driven results for light-quark connected and strange-plus-disconnected hadronic
g−2
short- and long-distance windows
Authors: Benton Genessa , Boito Diogo , Golterman Maarten , Keshavarzi Alexander , Maltman Kim , Peris Santiago
Published: February 2025

A key issue affecting the attempt to reduce the uncertainty on the Standard Model prediction for the muon anomalous magnetic moment is the current discrepancy between lattice-QCD and data-driven results for the hadronic vacuum polarization. Progress on this issue benefits from precise data-driven determinations of the isospin-limit light-quark-connected (lqc) and strange-plus-light-quark-disconnected (s+lqd) components of the related RBC/UKQCD windows. In this paper, using a strategy employed previously for the intermediate window, we provide data-driven results for the lqc and s+lqd components of the short- and long-distance RBC/UKQCD windows. Comparing these results with those from the lattice, we find significant discrepancies in the lqc parts but good agreement for the s+lqd components. We also explore the impact of recent CMD-3  e+e−→π+π− cross section results, demonstrating that an upward shift in the ρ-peak region of the type seen in the CMD-3 data serves to eliminate the discrepancies for the lqc components without compromising the good agreement between lattice and data-driven s+lqd results.

Published by the American Physical Society
2025
Probing neutrino millicharges at the European Spallation Source
Authors: Parada Alexander , Garcia G. Sanchez
Published: February 2025

We study the potential of a set of future detectors, proposed to be located at the European Spallation Source (ESS), to probe neutrino millicharges through coherent elastic neutrino-nucleus scattering. In particular, we focus on detectors with similar characteristics as those that are under development for operation at the ESS, including detection technologies based on cesium iodine, germanium, and noble gases. Under the considered conditions, we show that the Ge detector, with a lighter nuclear target mass with respect to CsI and a noble gas like Xe, is more efficient to constrain neutrino millicharges, reaching a sensitivity of ∼10−9e for diagonal neutrino millicharges, and ∼10−8e for the transition ones. In addition, we study the effects of including electron scattering processes for the CsI detector, achieving an expected sensitivity of ∼10−11e for the diagonal millicharges.

Published by the American Physical Society
2025
BPS chiral vortices in Maxwell-Higgs electrodynamics
Authors: Andrade J. , Casana Rodolfo , da Hora E.
Published: February 2025

We investigate the existence of Bogomol’nyi-Prasad-Sommerfield (BPS) structures in Maxwell-Higgs electrodynamics immersed in a chiral medium. The medium has its electromagnetic properties controlled by both a Chern-Simons term and a neutral scalar field. We implement the Bogomol’nyi-Prasad-Sommerfield technique and minimize the corresponding total energy. As a consequence, we get the BPS potential and the self-dual equations whose solutions saturate the Bogomol’nyi bound. In such a context, we look for vortices in two chiral media. The first one engenders localized configurations with an exponential decay similar to that of the standard Abrikosov-Nielsen-Olesen solutions. The second medium generates delocalized profiles whose tail follows a power-law decay. In both cases, we discuss the effects on the shape of the field profiles due to the chiral medium.

Published by the American Physical Society
2025
Application of boundary functionals of random processes in statistical physics
Authors: Ryazanov V. V.
Published: February 2025

The potential applications of boundary functionals of random processes, such as the extreme values of these processes, the moment of first reaching a fixed level, the value of the process at the moment of reaching the level, the moment of reaching extreme values, the time the process stays above a fixed level, and other functionals, are considered for the description of physical, chemical, and biological problems. Definitions of these functionals are provided, and characteristic functions are presented for the model with an exponential distribution of incoming demands. A generalization of these limitations is also considered. The potential uses of boundary functionals are demonstrated through examples such as a unicyclic network with affinity A, an asymmetric random walk, nonlinear diffusion, two-level model, Brownian motion, and multiple diffusing particles with reversible target-binding kinetics.

Published by the American Physical Society
2025
Atoms as Electron Accelerators for Measuring the Cross Section of
e+e−→Hadrons
Authors: Arias-Aragón Fernando , Darmé Luc , Grilli di Cortona Giovanni , Nardi Enrico
Published: February 2025

The hadronic vacuum polarization contribution to (g−2)μ can be determined via dispersive methods from e+e−→hadrons data. We propose a novel approach to measure the hadronic cross section σhad(s) as an alternative to the initial-state radiation and energy scan techniques, which relies on positron annihilation off atomic electrons of a high Z target (U238, Z=92). We show that by leveraging the relativistic electron velocities of the inner atomic shells, a high-intensity 12 GeV positron beam, such as the one foreseen at JLab, can allow measuring σhad(s) with high statistical accuracy from the two-pion threshold up to above s∼1  GeV.

Published by the American Physical Society
2025