bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractHemispherotomy 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

AbstractBackgroundOnchocerca 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 FindingsGerbils 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/SignificanceWhileO. 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 SummaryOnchocerca 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.
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

AbstractThe 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

ABSTRACTSchizophrenia 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

ABSTRACTThe 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

AbstractMotion 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 StatementRapidly 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

Abstract2-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 SummaryMethane 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

AbstractTransporters 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

ABSTRACTBackgroundWe conducted a systematic review and meta-analysis to examine the relationship between vitamin-D deficiency and depression in adolescents and young adults.MethodsWe 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.ResultsFrom 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%).LimitationsOur included studies ranged in sample size, which may influence the interpretation and generalizability of the results.ConclusionsOver 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

AbstractThe 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.