bluuebunny/crossref_metadata_2025 huggingface dataset:
BOLD Contrast Response Characteristics of Aberrant Voxels with Bilateral Visual Population Receptive Fields in Human Albinism
Authors: Duwell Ethan J. , Woertz Erica N. , Mathis Jedidiah , Carroll Joseph , DeYoe Edgar A.
Published: May 2024

Albinism is an inherited disorder characterized by disrupted melanin production in the eye, and often in the skin and hair. This retinal hypopigmentation is accompanied by pathological decussation of many temporal retinal afferents at the optic chiasm during development, ultimately resulting in partially superimposed representations of opposite visual hemifields in each cortical hemisphere. Within these aberrant regions of hemifield overlap, individual voxels have been shown to have bilateral, dual population receptive fields (pRFs) responding to roughly mirror-image locations across the vertical meridian. Nonetheless, how these two conflicting inputs combine to determine a voxel’s response to image contrast is still unknown. To address this, we stimulated the right and left hemifields with separately controlled sinusoidal gratings, each having a variety of contrasts (0, 8, 20, 45, 100%), and extracted voxel-wise BOLD response amplitudes to each contrast combination in visual areas V1-V3. We then compared voxels’ responses to each hemifield stimulated individually with conditions when both hemifields were stimulated simultaneously. We hypothesized that simultaneous stimulation of the two pRF components will result in either a suppressive or facilitative interaction. However, we found that BOLD responses to simultaneous stimulation appeared to reflect simple summation of the neural activity from the individual hemifield conditions. This suggests that the superimposed opposite hemifield representations do not interact. Thus, dual pRFs in albinism likely reflect two co-localized, but functionally independent populations of neurons each of which respond to a single hemifield. This finding is commensurate with psychophysical studies which have shown no clear perceptual interaction between opposite visual hemifields in human albinism.
High refresh rate display for natural monocular viewing in AOSLO psychophysics experiments
Authors: Moon Benjamin , Linebach Glory , Yang Angelina , Jenks Samantha K. , Rucci Michele , Poletti Martina , Rolland Jannick P.
Published: May 2024

By combining an external display operating at 360 frames per second with an Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) for human foveal imaging, we demonstrate color stimulus delivery at high spatial and temporal resolution in AOSLO psychophysics experiments. A custom pupil relay enables viewing of the stimulus through a 3-mm effective pupil diameter and provides refractive error correction from -8 to +4 diopters. Performance of the assembled and aligned pupil relay was validated by measuring the wavefront error across the field of view and correction range, and the as-built Strehl ratio was 0.64 or better. High-acuity stimuli were rendered on the external display and imaged through the pupil relay to demonstrate that spatial frequencies up to 54 cycles per degree, corresponding to 20/11 visual acuity, are resolved. The completed external display was then used to render fixation markers across the field of view of the monitor, and a continuous retinal montage spanning 9.4 by 5.4 degrees of visual angle was acquired with the AOSLO. We conducted eye-tracking experiments during free-viewing and high-acuity tasks with polychromatic images presented on the external display. Sub-arcminute eye position uncertainty was achieved, enabling precise localization of the line of sight on the monitor while simultaneously imaging the fine structure of the human central fovea. This high refresh rate display overcomes the temporal, spectral, and field of view limitations of AOSLO-based stimulus presentation, enabling natural monocular viewing of stimuli in psychophysics experiments conducted with AOSLO.
Oxygen-releasing nanodroplets relieve intratumoral hypoxia in head and neck cancer spheroids.
Authors: Xavierselvan Marvin , Bednarke Brooke , Shethia Ronak Tarun , Yang Vicky , Moses Leah , Mallidi Srivalleesha
Published: May 2024

Hypoxia in solid tumors, including head and neck cancer (HNC), contributes to treatment resistance, aggressive phenotypes, and poor clinical outcomes. Perfluorocarbon nanodroplets have emerged as promising oxygen carriers to alleviate tumor hypoxia. However, a thorough characterization of the hypoxia alleviation effects in terms of sustenance of oxygenated environments have not been thoroughly studied. In this study, we developed and characterized perfluoropentane nanodroplets (PFP NDs) for co-delivery of oxygen and the photoactivatable drug or photosensitizer benzoporphyrin derivative (BPD) to hypoxic HNC spheroids. The PFP NDs exhibited excellent stability, efficient oxygen loading/release, and biocompatibility. Using 3D multicellular tumor spheroids of FaDu and SCC9 HNC cells, we demonstrated the ability of oxygenated PFP NDs to penetrate the hypoxic core and alleviate hypoxia, as evidenced by reduced fluorescence of a hypoxia-sensing reagent and downregulation of hypoxia-inducible factors HIF-1α and HIF-2α. BPD-loaded PFP NDs successfully delivered the photosensitizer into the spheroid core in a time-dependent manner. These findings highlight the potential of PFP NDs as a co-delivery platform to overcome hypoxia-mediated treatment resistance and improve therapy outcomes in HNC.
Protective Effect of 2-Hydroxyestrone and 2-Hydroxyestradiol Against Chemically-Induced HepatotoxicityIn VitroandIn Vivo
Authors: Sun Xi , Hao Xiangyu , Jia Yichen , Zhang Qi , Zhu Yanyin , Yang Yong Xiao , Zhu Bao Ting
Published: May 2024

Ferroptosis is a form of regulated cell death closely associated with glutathione depletion and accumulation of reactive lipid peroxides. In the present study, we seek to determine whether 2-hydroxyestrone (2-OH-E1) and 2-hydroxyestradiol (2-OH-E2), two major metabolites of endogenous estrone and 17β-estradiol formed in liver by cytochrome P450 enzymes, can strongly protect against erastin– and RSL3-induced ferroptosis in hepatoma cells (H-4-II-E and HuH-7)in vitroand acetaminophen-induced mouse liver injuryin vivo. We find that 2-OH-E1and 2-OH-E2can protect, in a dose-dependent manner, H-4-II-E hepatoma cells against erastin/RSL3-induced ferroptosis. Similar protective effect of 2-OH-E1and 2-OH-E2against RSL3-induced ferroptosis is also observed in HuH-7 hepatoma cells. These two estrogen metabolites strongly reduce the levels of erastin– and/or RSL3-induced accumulation of cellular NO, ROS and lipid-ROS. Mechanistically, 2-OH-E1and 2-OH-E2protect cells against chemically-induced ferroptosis mainly by binding to cellular protein disulfide isomerase (PDI), and then inhibit its catalytic activity and reduce PDI-catalyzed formation of iNOS dimer, thereby abrogating cellular NO, ROS and lipid-ROS accumulation. Animal studies show that 2-OH-E1and 2-OH-E2can also exert a strong protection against acetaminophen-induced liver injury in mice. Interestingly, while estrone and 17β-estradiol display a very weak protective effect in cultured hepatoma cells, they exert a similarly-strong protective effect as 2-OH-E1and 2-OH-E2in vivo, suggesting that the metabolic conversion of estrone and 17β-estradiol to 2-OH-E1and 2-OH-E2contributes importantly to their hepatoprotective effect. The results of this study reveal that 2-OH-E1and 2-OH-E2are important endogenous factors for protection against chemically-induced liver injuryin vivo.
The antimicrobial peptides pipeline: a bacteria-centric AMP predictor
Authors: Veldsman Werner Pieter , Zhang Qi , Zhao Qian , Zhang Eric Lu
Published: May 2024

Antimicrobial peptides (AMPs), unlike antibiotics, are encoded in genomes. AMPs are exported from the cell after expression and translation. In the case of bacteria, the exported peptides target other microbes to give the producing bacterium a competitive edge. While AMPs are sought after for their similar antimicrobial activity to traditional antibiotics, it is difficult to predict which combinations of amino acids will confer antimicrobial activity. Many computer algorithms have been designed to predict whether a sequence of amino acids will exhibit antimicrobial activity, but the vast majority of validated AMPs in databases are still of eukaryotic origin. This defies common sense since the vast majority of life on earth is prokaryotic. The antimicrobial peptides pipeline, presented here, is a bacteria-centric AMP predictor that predicts AMPs by taking design inspiration from the sequence properties of bacterial genomes with the intention to improve detection of naturally occurring bacterial AMPs. The pipeline integrates multiple concepts of comparative biology to search for candidate AMPs at the primary, secondary and tertiary peptide structure level. Results showed that the antimicrobial peptides pipeline identifies known AMPs that are missed by state-of-the-art AMP predictors, and that the pipeline yields more AMP candidates from real bacterial genomes than from fake genomes, with the rate of AMP detection being significantly higher in the genomes of seven nosocomial pathogens than in the fake genomes.
Direct and Indirect Salt Effects on Homotypic Phase Separation
Authors: MacAinsh Matthew , Dey Souvik , Zhou Huan-Xiang
Published: May 2024

The low-complexity domain of hnRNPA1 (A1-LCD) phase separates in a salt-dependent manner. Unlike many intrinsically disordered proteins (IDPs) whose phase separation is suppressed by increasing salt concentrations, the phase separation of A1-LCD is promoted by > 100 mM NaCl. To investigate the atypical salt effect on A1-LCD phase separation, we carried out all-atom molecular dynamics simulations of systems comprising multiple A1-LCD chains at NaCl concentrations from 50 to 1000 mM NaCl. The ions occupy first-shell as well as more distant sites around the IDP chains, with Arg sidechains and backbone carbonyls the favored partners of Cl-and Na+, respectively. They play two direct roles in driving A1-LCD condensation. The first is to neutralize the high net charge of the protein (+9) by an excess of bound Cl-over Na+; the second is to bridge between A1-LCD chains, thereby fortifying the intermolecular interaction networks in the dense phase. At high concentrations, NaCl also indirectly strengthens π-π, cation-π, and amino-π interactions, by drawing water away from the interaction partners. Therefore, at low salt, A1-LCD is prevented from phase separation by net charge repulsion; at intermediate concentrations, NaCl neutralizes enough of the net charge while also bridging IDP chains to drive phase separation. This drive becomes even stronger at high salt due to strengthened π-type interactions. Based on this understanding, four classes of salt dependence of IDP phase separation can be predicted from amino-acid composition.
Histone H2B isoformH2bc27is expressed in the developing brain of mouse embryos
Authors: Egashira Saki , Maehara Kazumitsu , Tanaka Kaori , Nakamura Mako , Takemoto Tatsuya , Ohkawa Yasuyuki , Harada Akihito
Published: May 2024

Histones bind directly to DNA and play a role in regulating gene expression mediated by chromatin structure. DNA sequences of these histone genes are quite similar, which has hindered individual analyses. The exact function of the 13 different isoforms of histone H2B remains unclear. In this report, a comprehensive gene expression analysis of the H2B isoforms, focusing on tissue specificity, was conducted. We generated mice lacking the H2bc27 gene, which exhibited brain-specific expression of E14.5, and proceeded to characterize the brain tissue. The phenotype ofH2bc27knockout brains was similar to that of wild-type brains, yet transcriptome analysis indicated thatH2bc27is associated with regulating the expression of several functional genes involved in mouse brain development. The methods used in this study may serve to facilitate comprehensive H2B isoform analysis.
Cold exposure transiently increases resistance ofArabidopsis thalianaagainst the fungal pathogenBotrytis cinerea
Authors: Schütte Dominic , Remmo Abdulmalek , Baier Margarete , Griebel Thomas
Published: May 2024

A sudden cold exposure (4°C, 24 h) primes resistance ofArabidopsis thalianaagainst the virulent biotrophic pathogenPseudomonas syringaepv.tomatoDC3000 (Pst) for several days. This effect is mediated by chloroplast cold sensing and the activity of stromal and thylakoid-bound ascorbate peroxidases (sAPX/tAPX). In this study, we investigated the impact of such cold exposure on plant defence against the necrotrophic fungusBotrytis cinerea. Plant resistance was transiently enhanced if theB. cinereainfection occurred immediately after the cold exposure, but this cold-enhancedB. cinerearesistance was absent when the cold treatment and the infection were separated by 5 days at normal growth conditions. Plastid ascorbate peroxidases partially contributed to the transient cold-enhanced resistance against the necrotrophic fungus. In response toB. cinerea, the levels of reactive oxygen species (ROS) were significantly higher in cold-pretreated Arabidopsis leaves. Pathogen-triggered ROS levels varied in the absence of sAPX, highlighting the strong capacity for sAPX-dependent ROS regulation in the chloroplast stroma. The cold-enhanced resistance againstB. cinereawas associated with cold-induced plant cell wall modifications, including sAPX-dependent callose formation and significant lignification in cold-treated Arabidopsis leaves.

Funding

This work was supported by the German Research Foundation (CRC973/C4) and the FU Berlin.
The global prevalence and genetic spectrum of primary carnitine deficiency
Authors: Sun Liu , Wu Hang-Jing
Published: May 2024

Background

Primary carnitine deficiency (PCD) is an autosomal recessive rare disorder of carnitine cycle and carnitine transport caused by mutations in the SLC22A5 gene. The prevalence of PCD is unclear. This study aimed to estimate the carrier frequency and genetic prevalence of PCD using Genome Aggregation Database (gnomAD) data.

Methods

The pathogenicity of SLC22A5 variants was interpreted according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The minor allele frequency (MAF) of SLC22A5 gene disease-causing variants in 807,162 unique individuals was examined to estimate the global prevalence of PCD in five major ethnicities: African (afr), Admixed American (amr), East Asian (eas), Non-Finnish European (nfe) and South Asian (sas). The global and population-specific carrier frequencies and genetic prevalence of PCD were calculated using the Hardy–Weinberg equation.

Results

In total, 195 pathogenic/likely pathogenic variants (PV/LPV) were identified according to ACMG standards and guidelines. The global carrier frequency and genetic prevalence of PCD were 1/88 and 1/31,260, respectively.

Conclusions

The prevalence of PCD is estimated to be 1/30,000 globally, with a range of between 1/20,000 and 1/70,000 depending on ethnicity.
Weight Gain Following a Diagnosis of Anti-neutrophil Cytoplasm Antibody-Associated Vasculitis
Authors: Salehi Tania , French Thomas , Farrah Tariq E , Dhaun Neeraj , Hunter Robert W
Published: May 2024

Objectives

Patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) are at increased long-term risk of cardiometabolic diseases. The prevalence of obesity in AAV has not been well documented. We aimed to characterise change in body weight following a diagnosis of active AAV and to determine the risk factors for this.

Methods

We examined data from a single-centre registry of patients with AAV, diagnosed between 2003 and 2023. We evaluated changes in body weight and BMI following diagnosis. Using linear regression, we identified factors contributing to an increase in BMI at six-months. Logistic regression was used to define predictors for obesity at six-months.

Results

Two-hundred and fifteen patients with active AAV were included in the analysis. Patients experienced a mean gain in body weight of 5.2% in the first six-months; this was maintained for at least two-years. 64.1% of patients were overweight or obese at six-months. Weight gain was greater following first presentation of AAV compared to relapsing disease. Baseline factors associated with an increase in BMI at six-months included higher eGFR (β=0.70 [0.36-1.03], P<0.001) and earlier year of presentation (β=0.38 [0.08-0.69], P=0.008). Higher eGFR (aOR=1.36 (1.08-2.72), P<0.001) and baseline BMI (aOR=2.57 (1.81-3.64), P<0.001) were associated with an increased likelihood of obesity at six-months.

Conclusion

Weight gain is common following a diagnosis of active AAV. This is less pronounced than it was two-decades ago. Better kidney function and higher baseline BMI are associated with a greater risk of being obese at six-months. Management of AAV should include risk mitigation for developing an unhealthy high BMI.

Key messages

Weight gain and an unhealthy high BMI are prevalent following diagnosis of active AAV.

Higher baseline eGFR is associated with greater weight-gain in the first six-months following diagnosis.

Weight gain is less pronounced following treatment of relapsing disease compared to initial presentation.
Prevalence of Depressive symptoms and its associated factors among elderly living in old age homes of Kathmandu Metropolitan City, Nepal
Authors: Maharjan Sanju , Tiwari Nujan , Bista Sita , Basel Prem
Published: May 2024

Background

Depressive symptoms have become a global public health problem, with a predominant effect on the elderly people. The studies on mental health status of elderly people in Nepal are quite limited. In this study, we aim to assess the prevalence of depressive symptoms and its associated factors among the elderly living in public old age homes of Kathmandu Metropolitan City in Nepal.

Methodology

A cross-sectional study was conducted including 142 adults aged 60 years and above recruited through proportional simple random sampling from six old age homes. The 15 item-Geriatric Depression Scale(GDS) was used to assess the depressive symptoms among the participants. Associated factors were tested using Chi-square test; and a p-value of less than 0.05 with a confidence interval of 95% was used for statistical significance.

Results

More than half of the study participants, 58.5% (95% CI: 49.9%-66.7%) were found to have depressive symptoms. Among them, 38.7% had mild symptoms, 16.2% had moderate symptoms and 3.5% had severe symptoms. Age (OR = 2.25, 95% CI: 1.08-4.66), sex (OR = 2.36, 95% CI: 1.17-4.75), past family type (OR = 0.44, 0.22-0.89), chronic physical health problem (OR = 0.34, 95% CI: 0.12-0.98) and feelings of loneliness were found to have significant association with depressive symptoms among the elderly population.

Conclusion

The prevalence of depressive symptoms among the elderly in old age homes in Kathmandu Metropolitan City is quite high and a concerning issue that requires targeted mental health programs and interventions in order to bring about a positive shift in their mental health condition.
Ventricle stimulation as a potential gold-standard control stimulation site for transcranial focused ultrasound stimulation
Authors: Atkinson-Clement Cyril , Kaiser Marcus , Lambon Ralph Matthew A. , Jung JeYoung
Published: May 2024

This research investigates whether ventricular-focused ultrasound stimulation (ventricle-FUS) can serve as an effective control in studies using transcranial FUS, a non-invasive technology for brain modulation. FUS has notable potential for therapeutic applications but requires a robust control to accurately assess its effects. We evaluated the effectiveness of ventricle-FUS, as an active, non-cerebrum control for FUS research, comparing it to sham stimulation. We conducted a comprehensive assessment of ventricle-FUS, employing both questionnaires and multiple neuroimaging metrics such as grey matter and white matter volumes, and functional connectivity. Ventricle-FUS did not alter any of these metrics, thereby successfully retaining the auditory, somatosensory, and experiential elements of FUS without affecting brain structure or function. Importantly, participants were unable to distinguish whether they received ventricle-FUS or sham FUS. Our findings confirm that ventricle-FUS establishes it as a reliable control approach in FUS research, crucial for advancing its therapeutic applications.
Overlapping role of synaptophysin and synaptogyrin family proteins in determining the small size of synaptic vesicles
Authors: Park Daehun , Fujise Kenshiro , Wu Yumei , Luján Rafael , Del Olmo-Cabrera Sergio , Wesseling John F. , De Camilli Pietro
Published: May 2024

Members of the synaptophysin and synaptogyrin family are vesicle proteins with four transmembrane domains. In spite of their abundance in synaptic vesicle (SV) membranes, their role remains elusive and only mild defects at the cellular and organismal level are observed in mice lacking one or more family members. Here, we show that co-expression with synapsin of each of the four brain-enriched members of this family - synaptophysin, synaptoporin, synaptogyrin1 and synaptogyrin3 - in fibroblasts is sufficient to generate clusters of small vesicles in the same size range of SVs. Moreover, mice lacking all these four proteins have larger SVs. We conclude that synaptophysin and synaptogyrin family proteins play an overlapping function in the biogenesis of SVs and in determining their small size.
Unveiling the hidden electroencephalographical rhythms during development: aperiodic and periodic activity in healthy subjects
Authors: Angulo-Ruiz Brenda Y. , Rodríguez-Martínez Elena I. , Muñoz Vanesa , Gómez Carlos M.
Published: May 2024

Objective

The study analyzes power spectral density (PSD) components, aperiodic (AP) and periodic (P) activity, in resting-state EEG of 240 healthy subjects from 6 to 29 years old, divided into 4 groups.

Methods

We calculate AP and P components using the (Fitting Oscillations and One-Over-f (FOOOF))plugging in EEGLAB. All PSD components were calculated from 1-45Hz. Topography analysis, Spearman correlations, and regression analysis with age were computed for all the components.

Results

AP and P activity show different topography across frequencies and age groups. Age-related decreases in AP exponent and offset parameters lead to reduced power, while P power decreases (1-6Hz) and increases (10-15Hz) with age.

Conclusions

We support the distinction between the AP and P components of the PSD and its possible functional changes with age. AP power is dominant in the configuration of the canonical EEG rhythms topography, although P contribution to topography is embedded in the canonical EEG topography. Some EEG canonical characteristics are similar to those of P component, as topographies of EEG rhythms (embedded) and increases in oscillatory frequency with age.

Significance

We support that spectral power parameterization improves the interpretation and neurophysiological and functional accuracy of brain processes.

Highlights

Differential topography for aperiodic and periodic EEG components.

Power decrease in aperiodic component (exponent and offset) with age.

Decrease (lower frequencies) and increase (higher frequencies) of periodic component.
Dysregulation of synaptic transcripts underlies network abnormalities in ALS patient-derived motor neurons
Authors: Kollstrøm Anna M. , Christiansen Nicholas , Sandvig Axel , Sandvig Ioanna
Published: May 2024

Amyotrophic lateral sclerosis (ALS) is characterized by dysfunction and loss of upper and lower motor neurons. Several studies have identified structural and functional alterations in the motor neurons before the manifestation of symptoms, yet the underlying cause of such alterations and how they contribute to the progressive degeneration of affected motor neuron networks remain unclear. Importantly, the short and long-term spatiotemporal dynamics of neuronal network activity make it challenging to discern how ALS-related network reconfigurations emerge and evolve. To address this, we systematically monitored the structural and functional dynamics of motor neuron networks with a confirmed endogenous C9orf72 mutation. We show that ALS patient-derived motor neurons display time-dependent neural network dysfunction, specifically reduced firing rate and spike amplitude, impaired bursting, but higher overall synchrony in network activity. These changes coincided with altered neurite outgrowth and branching within the networks. Moreover, transcriptional analyses revealed dysregulation of molecular pathways involved in synaptic development and maintenance, neurite outgrowth and cell adhesion, suggesting impaired synaptic stabilization. This study identifies early synaptic dysfunction as a contributing mechanism resulting in network-wide structural and functional compensation, which may over time render the networks vulnerable to neurodegeneration.
Individual differences in the expression and control of anger are encoded in the same fronto-temporal GM-WM network
Authors: Grecucci Alessandro , Geraci Francesca , Munari Ellyson , Yi Xiaoping , Salvato Gerardo , Messina Irene
Published: May 2024

Anger can be deconstructed into distinct components: a temporary emotional state (state anger), a stable personality trait (trait anger), a tendency to outwardly express it (anger-out), or to internally suppress it (anger-in), and the capability to manage it (anger control). These aspects exhibit individual differences that vary across a continuum. Notably, the capacity to express and control anger are of great importance to modulate our reactions in interpersonal situations. The aim of this study was to test the hypothesis that anger expression and control are negatively correlated and that both can be decoded by the same patterns of grey and white matter features of a fronto-temporal brain network. To this aim, a data fusion unsupervised machine learning technique, known as transposed Independent Vector Analysis (tIVA), was used to decompose the brain into covarying GM-WM networks and then backward regression was used to predict both anger expression and control from a sample of 212 healthy subjects. Confirming our hypothesis, results showed that anger control and anger expression are negatively correlated, the more individuals control anger, the less they externalize it. At the neural level, individual differences in anger expression and control can be predicted by the same GM-WM network. As expected, this network included fronto-temporal regions as well as the cingulate, the insula and the precuneus. The higher the concentration of GM-WM in this brain network, the higher level of externalization of anger, and the lower the anger control. These results expand previous findings regarding the neural bases of anger by showing that individual differences in anger control and expression can be predicted by morphometric features.
DENOISING: Dynamic Enhancement and Noise Overcoming in Multimodal Neural Observations via High-density CMOS-based Biosensors
Authors: Hu Xin , Emery Brett Addison , Khanzada Shahrukh , Amin Hayder
Published: May 2024

Large-scale multimodal neural recordings on high-density biosensing microelectrode arrays (HD-MEAs) offer unprecedented insights into the dynamic interactions and connectivity across various brain networks. However, the fidelity of these recordings is frequently compromised by pervasive noise, which obscures meaningful neural information and complicates data analysis. To address this challenge, we introduce DENOISING, a versatile data-derived computational engine engineered to adjust thresholds adaptively based on large-scale extracellular signal characteristics and noise levels. This facilitates the separation of signal and noise components without reliance on specific data transformations. Uniquely capable of handling a diverse array of noise types (electrical, mechanical, and environmental) and multidimensional neural signals, including stationary and non-stationary oscillatory local field potential (LFP) and spiking activity, DENOISING presents an adaptable solution applicable across different recording modalities and brain networks. Applying DENOISING to large-scale neural recordings from mice hippocampal and olfactory bulb networks yielded enhanced signal-to-noise ratio (SNR) of LFP and spike firing patterns compared to those computed from raw data. Comparative analysis with existing state-of-the-art denoising methods, employing SNR and root mean square noise (RMS), underscores DENOISING’s performance in improving data quality and reliability. Through experimental and computational approaches, we validate that DENOISING improves signal clarity and data interpretation by effectively mitigating independent noise in spatiotemporally structured multimodal datasets, thus unlocking new dimensions in understanding neural connectivity and functional dynamics.
Normative evidence weighing and accumulation in correlated environments
Authors: Tardiff Nathan , Kang Jiwon , Gold Joshua I.
Published: May 2024

The brain forms certain deliberative decisions following normative principles related to how sensory observations are weighed and accumulated over time. Previously we showed that these principles can account for how people adapt their decisions to the temporal dynamics of the observations (Glaze et al., 2015). Here we show that this adaptability extends to accounting for correlations in the observations, which can have a dramatic impact on the weight of evidence provided by those observations. We tested online human participants on a novel visual-discrimination task with pairwise-correlated observations. With minimal training, the participants adapted to uncued, trial-by-trial changes in the correlations and produced decisions based on an approximately normative weighing and accumulation of evidence. The results highlight the robustness of our brain’s ability to process sensory observations with respect to not just their physical features but also the weight of evidence they provide for a given decision.
StablePlasmodium falciparummerozoite surface protein-1 allelic diversity despite decreasing parasitemia in children with multiple malaria infections
Authors: Yaa Reuben Mangi , Kimenyi Kelvin M , Antonio Palasciano H , Obiero George , Ochola-Oyier Lynette Isabella
Published: May 2024

Individuals experiencing recurrent malaria infections encounter a variety of alleles with each new infection. This ongoing allelic diversity influences the development of naturally acquired immunity and it can inform vaccine efficacy. To investigate the diversity and infection variability,Plasmodium falciparummerozoite surface protein 1 (Pfmsp1), a crucial protein for parasite invasion and immune response, was assessed in parasites isolated from children with repeated malaria episodes. A total of eleven microhaplotypes were observed across all malaria episodes. There were 4 prevalent microhaplotypes, E-KSNG-L, Q-KSNG-L, Q-KSNG-F, and Q-KNNG-L, in the population. Conversely, microhaplotypes such as E-KSSR-L, E-KNNG-L, E-KSSG-L, E-TSSR-L (3D7), Q-TSSR-L, E-TSSG-L, and E-KSNG-F were rare and maintained at low frequencies. High allelic replacements were observed, however some individuals experienced consecutive re-infections with the same microhaplotype. Notably,Pfmsp119allelic diversity as measured by haplotype diversity was stable, while nucleotide diversity decreased over time with decreasing parasitemia. ParasitePfmsp119allelic diversity remained stable over the multiple malaria episodes, despite declining parasitaemia levels and ongoing immune development. In addition, our findings reveal dynamicPfmsp119allelic replacements across parasite infection episodes, with initial immune responses to prevalent variants potentially waning over time, allowing for re-infections. Overall, our findings emphasize that protective immunity to malaria involves complex immune responses targeting multiple alleles that wane over time and thus the development of sterilizing immunity is a challenge.
Theoretical proposal for restoration of hand motor function utilizing plasticity of motor-cortical interhemispheric interaction
Authors: Nakano Hideki , Tang Yandi , Morita Tomoyo , Naito Eiichi
Published: May 2024

After stroke, the poorer recovery of motor function of upper extremities compared to other body parts is a longstanding problem. Based on our recent functional MRI evidence on healthy volunteers, this perspective paper proposes systematic hand motor rehabilitation utilizing the plasticity of interhemispheric interaction between motor cortices and following its developmental rule. We first discuss the effectiveness of proprioceptive intervention on the paralyzed (immobile) hand synchronized with voluntary movement of the intact hand to induce muscle activity in the paretic hand. In healthy participants, we show that this bilateral proprioceptive-motor coupling intervention activates the bilateral motor cortices (= bilaterally active mode), facilitates interhemispheric motor-cortical functional connectivity, and augments muscle activity of the passively-moved hand. Next, we propose training both hands to perform different movements, which would be effective for stroke patients who become able to manage to move the paretic hand. This bilaterally different movement training may guide the motor cortices into left-right independent mode to improve interhemispheric inhibition and hand dexterity, because we have shown in healthy older adults that this training reactivates motor-cortical interhemispheric inhibition (= left-right independent mode) declined with age, and can improve hand dexterity. Transition of both motor cortices from the bilaterally active mode to the left-right independent mode is a developmental rule of hand motor function and a common feature of motor function recovery after stroke. Hence, incorporating the brain’s inherent capacity for spontaneous recovery and adhering to developmental principles may be crucial considerations in designing effective rehabilitation strategies.
Dynamics of EEG Microstates Change Across the Spectrum of Disorders of Consciousness
Authors: Manasova Dragana , Sanz Perl Yonatan , Bruno Nicolas Marcelo , Valente Melanie , Rohaut Benjamin , Tagliazucchi Enzo , Naccache Lionel , Raimondo Federico , Sitt Jacobo D.
Published: May 2024

As a response to the environment and internal signals, brain networks reorganize on a sub-second scale. To capture this reorganization in patients with disorders of consciousness and understand their residual brain activity, we investigated the dynamics of electroencephalography (EEG) microstates. We analyze EEG microstate markers to quantify the periods of semi-stable topographies and the large-scale cortical networks they may reflect. To achieve this, EEG samples are clustered into four groups and then fit back into each time sample. We then obtain a time series of maps with different frequencies of occurrence and duration. One such occurrence of a map with a given duration is called a microstate. The goal of this work is to study the dynamics of these topographical patterns across patients with disorders of consciousness. Using the microstate time series, we calculate static and dynamic markers. In contrast to the static, the dynamic metrics depend on the specific temporal sequences of the maps. The static measure Ratio of Total Time covered (RTT) shows differences between healthy controls and patients, however, no differences were observed between the groups of patients. In contrast, some dynamic markers capture inter-patient group differences. The dynamic markers we investigated are Mean Microstate Durations (MMD), Microstate Duration Variances (MDV), Microstate Transition Matrices (MTM), and Entropy Production (EP). The MMD and MDV decrease with the state of consciousness, whereas the MTM non-diagonal transitions and EP increase. In other words, DoC patients have slower and closer to equilibrium (time-reversible) brain dynamics. In conclusion, static and dynamic EEG microstate metrics differ across consciousness levels, with the latter capturing the subtitler differences between groups of patients with disorders of consciousness.

Abbreviated summary

This study investigates EEG microstate dynamics in patients with disorders of consciousness (DoC) to understand residual brain activity and network reorganization. Entropy production, in addition to static markers, differs between patients and healthy controls, whereas the rest of the dynamic markers show differences across patient groups.
Learning Conjunctive Representations
Authors: Pettersen Markus , Rogge Frederik , Lepperød Mikkel Elle
Published: May 2024

Hippocampal place cells are known for their spatially selective firing patterns, which has led to the suggestion that they encode an animal’s location. However, place cells also respond to contextual cues, such as smell. Furthermore, they have the ability to remap, wherein the firing fields and rates of cells change in response to environmental changes. How place cell responses emerge, and how these representations remap is not fully understood. In this work, we propose a similarity-based objective function that translates proximity in space, to proximity in representation. We show that a neural network trained to minimize the proposed objective learns place-like representations. We also show that the proposed objective is trivially extended to include other sources of information, such as context information, in the same way. When trained to encode multiple contexts, networks learn distinct representations, exhibiting remapping behaviors between contexts. The proposed objective is invariant to orthogonal transformations. Such transformations of the original trained representation (e.g. rotations), therefore yield new representations distinct from the original, without explicit relearning, akin to remapping. Our findings shed new light on the formation and encoding properties of place cells, and also demonstrate an interesting case of representational reuse.
A thalamic perspective of (un)consciousness in pharmacological and pathological states in humans
Authors: Szocs Dorottya , Lyu Dian , Luppi Andrea I. , Coppola Peter , Woodrow Rebecca , Williams Guy B. , Allanson Judith , Pickard John D. , Owen Adrian M. , Naci Lorina , Menon David K. , Stamatakis Emmanuel A.
Published: May 2024

Currently, there is substantial ongoing discussion around the functional role of the thalamus in consciousness. What is missing in the literature, however, is a systematic investigation of the relevance of specific thalamic nuclei in pharmacologically and pathologically altered states of consciousness in humans. Using functional neuroimaging in both healthy anaesthetised volunteers and patients with disorders of consciousness (DOC), we sought to identify which specific thalamic subregions in both cohorts may be differentially significant for loss of consciousness. Our findings revealed that the pulvinar (Pu) and ventral-latero-ventral (VLV) nuclei, in anaesthesia, and the VLV, in DOC, had distinct functional connectivity patterns related to the default mode and somatomotor networks. Remarkably, among all nuclei, the Pu was found to have the strongest functional connectivity change with anaesthetic-induced loss of consciousness, while in DOC patients, we found the VLV revealed the strongest connectivity change in comparison with healthy controls. Furthermore, we provide evidence that this neural connectivity biomarker in patients also mirrors the changes observed at the behavioural level, which could have clinical implications for targeted deep brain stimulation in therapy for DOC.
Microbiota in the ptarmigan intestine - an Inuit delicacy and its potential in popular cuisine
Authors: Bjørnsen Mads Bjørn , Valerón Nabila Rodríguez , Vásquez Diego Prado , Velasco Esther Merino , Hansen Anders Johannes , Hauptmann Aviaja Lyberth
Published: May 2024

The consumption of prey intestines and their content, known as gastrophagy, is well-documented among Arctic Indigenous peoples, particularly Inuit. In Greenland, Inuit consume intestines from various animals, including the ptarmigan, a small herbivorous grouse bird. While gastrophagy provides the potential to transfer a large number of intestinal microorganisms from prey to predator, including to the human gut, its microbial implications remain to be investigated. This study addresses this gap by investigating the microbial composition of the Greenlandic rock ptarmigan’s gastrointestinal tract by analyzing the crop, stomach, and intestines while also comparing it with the microbiota found in garum, a fermented sauce made from ptarmigan meat and intestines. Through 16S rRNA gene sequencing, we assessed whether garum made from ptarmigan intestines provides access to microbial diversity otherwise only accessible through gastrophagy. Our findings reveal that garum made from ptarmigan intestines displayed distinct flavors and microbial composition similar to that found in the ptarmigan gut and intestines, highlighting the potential role of fermented products in mediating food microbial diversity associated with Indigenous food practices. Furthermore, our study underscores the broader importance of understanding microbial diversity in different food systems, particularly in the context of shifting dietary patterns and concerns about diminishing food microbial diversity. By elucidating the microbial richness gained through gastrophagy this research contributes to a deeper understanding of traditional and Indigenous foodways and their implications for human gut health.
Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm
Authors: Ee Ly-sha , Medina-Cano Dani , Uyehara Christopher , Schwarz Clayton , Goetzler Emily , Salataj Eralda , Polyzos Alexander , Madhuranath Subhashini , Evans Todd , Hadjantonakis Kat , Apostolou Effie , Vierbuchen Tommy , Stadtfeld Matthias
Published: May 2024

The molecular mechanisms that drive essential developmental patterning events in the mammalian embryo remain poorly understood. To generate a conceptual framework for gene regulatory processes during germ layer specification, we analyzed transcription factor (TF) expression kinetics around gastrulation and during in vitro differentiation. This approach identified Otx2 as a candidate regulator of definitive endoderm (DE), the precursor of all gut-derived tissues. Analysis of multipurpose degron alleles in gastruloid and directed differentiation models revealed that loss of OTX2 before or after DE specification alters the expression of core components and targets of specific cellular signaling pathways, perturbs adhesion and migration programs as well as de-represses regulators of other lineages, resulting in impaired foregut specification. Key targets of OTX2 are conserved in human DE. Mechanistically, OTX2 is required to establish chromatin accessibility at candidate enhancers, which regulate genes critical to establishing an anterior cell identity in the developing gut. Our results provide a working model for the progressive establishment of spatiotemporal cell identity by developmental TFs across germ layers and species, which may facilitate the generation of gut cell types for regenerative medicine applications.
Diverse perceptual biases emerge from Hebbian plasticity in a recurrent neural network model
Authors: Schönsberg Francesca , Giana Davide , Chopra Yukti , Diamond Mathew , Goldt Sebastian
Published: May 2024

Perceptual biases offer a glimpse into how the brain processes sensory stimuli. While psycho-physics has uncovered systematic biases such as contraction (stored information shifts towards a central tendency), and repulsion (the current percept shifts away from recent percepts), a unifying neural network model for how such seemingly distinct biases emerge from learning is lacking. Here, we show that both contractive and repulsive biases emerge from continuous Hebbian plasticity in a single recurrent neural network. We test the model in four different datasets, two sensory modalities and three experimental paradigms: two working memory tasks, a reference memory task, and a novel “one-back task” that we designed to test the robustness of the model. We find excellent agreement between model predictions and experimental data without fine-tuning the model to any particular paradigm. These results show that apparently contradictory perceptual biases can in fact emerge from a simple local learning rule in a single recurrent region of the brain.
Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis
Authors: Blackwell Amanda Mixon , Jami-Alahmadi Yasaman , Nasamu Armiyaw S. , Kudo Shota , Senoo Akinobu , Slam Celine , Tsumoto Kouhei , Wohlschlegel James A. , Caaveiro Jose M. M. , Goldberg Daniel E. , Sigala Paul A.
Published: May 2024

Malaria parasites have evolved unusual metabolic adaptations that specialize them for growth within heme-rich human erythrocytes. During blood-stage infection,Plasmodium falciparumparasites internalize and digest abundant host hemoglobin within the digestive vacuole. This massive catabolic process generates copious free heme, most of which is biomineralized into inert hemozoin. Parasites also express a divergent heme oxygenase (HO)-like protein (PfHO) that lacks key active-site residues and has lost canonical HO activity. The cellular role of this unusual protein that underpins its retention by parasites has been unknown. To unravel PfHO function, we first determined a 2.8 Å-resolution X-ray structure that revealed a highly α-helical fold indicative of distant HO homology. Localization studies unveiled PfHO targeting to the apicoplast organelle, where it is imported and undergoes N-terminal processing but retains most of the electropositive transit peptide. We observed that conditional knockdown of PfHO was lethal to parasites, which died from defective apicoplast biogenesis and impaired isoprenoid-precursor synthesis. Complementation and molecular-interaction studies revealed an essential role for the electropositive N-terminus of PfHO, which selectively associates with the apicoplast genome and enzymes involved in nucleic acid metabolism and gene expression. PfHO knockdown resulted in a specific deficiency in levels of apicoplast-encoded RNA but not DNA. These studies reveal an essential function for PfHO in apicoplast maintenance and suggest thatPlasmodiumrepurposed the conserved HO scaffold from its canonical heme-degrading function in the ancestral chloroplast to fulfill a critical adaptive role in organelle gene expression.
Carbapenem-induced β-lactamase-isoform expression trends inAcinetobacter baumannii
Authors: Benin Bogdan M. , Hillyer Trae , Aguirre Noah , Sham Yuk Yin , Willard Belinda , Shin Woo Shik
Published: May 2024

Carbapenem-resistantAcinetobacter baumannii(CRAb) is an urgent bacterial threat to public health, with only a few treatment options and a >50% fatality rate. Although several resistance mechanisms are understood, the appearance of these mutations is generally considered stochastic. Recent reports have, however, begun to challenge this assumption. Here, we demonstrate that independent samples of Ab, exposed to different carbapenems with escalating concentrations, show concentration- and carbapenem-dependent trends in β-lactamase-isoform expression. This result, based on the isoforms identified through label-free-quantification LC-MS/MS measurements of cell-free, gel-separated β-lactamases, suggests that the appearance of antibiotic resistance may be somewhat non-stochastic. Specifically, several minor AmpC/ADC β-lactamase-isoforms were found to exhibit both dose- and carbapenem-dependent expression, suggesting the possibility of non-stochastic mutations. Additionally, these also have high sequence similarity to major expressed isoforms, indicating a potential path over which resistance occurred in independent samples. Antibiotic resistance maybe somewhat antibiotic-directed by a hitherto unknown mechanism and further investigation may lead to new strategies for mitigating antibiotic resistance.

Teaser

The emergence of antibiotic-resistant β-lactamase proteins from mutations may exhibit patterns based on specific antibiotics.