bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Update on Applications of Quaternary Ammonium Silane as an Antibacterial Biomaterial: A Novel Drug Delivery Approach in Dentistry
Authors: Bapat Ranjeet Ajit , Parolia Abhishek , Chaubal Tanay , Yang Ho Jan , Kesharwani Prashant , Phaik Khoo Suan , Lin Seow Liang , Daood Umer
Published: September 2022

Quaternary ammonium silane [(QAS), codename – k21] is a novel biomaterial developed by sol-gel process having broad spectrum antimicrobial activities with low cytotoxicity. It has been used in various concentrations with maximum antimicrobial efficacy and biocompatibility. The antimicrobial mechanism is displayed via contact killing, causing conformational changes within the bacterial cell membrane, inhibiting Sortase-A enzyme, and causing cell disturbances due to osmotic changes. The compound can attach to S1' pockets on matrix metalloproteinases (MMPs), leading to massive MMP enzyme inhibition, making it one of the most potent protease inhibitors. Quaternary ammonium silane has been synthesized and used in dentistry to eliminate the biofilm from dental tissues. QAS has been tested for its antibacterial activity as a cavity disinfectant, endodontic irrigant, restorative and root canal medication, and a nanocarrier for drug delivery approaches. The review is first of its kind that aims to discuss applications of QAS as a novel antibacterial biomaterial for dental applications along with discussions on its cytotoxic effects and future prospects in dentistry.
Minimal impacts on the wheat microbiome when Trichoderma gamsii T6085 is applied as a biocontrol agent to manage fusarium head blight disease
Authors: Alukumbura Arshani S. , Bigi Alessandro , Sarrocco Sabrina , Fernando W. G. Dilantha , Vannacci Giovanni , Mazzoncini Marco , Bakker Matthew G.
Published: September 2022

Fusarium head blight (FHB) is a major fungal disease that causes severe yield and quality loss in wheat. Biological control can be integrated with other management strategies to control FHB. For this purpose, Trichoderma gamsii strain T6085 is a potential biocontrol agent to limit the infection of F. graminearum and F. culmorum in wheat. However, the possible impacts of T. gamsii T6085 on the broader microbiome associated with the wheat plant are not currently understood. Therefore, we identified bacteria and fungi associated with different wheat tissues, including assessment of their relative abundances and dynamics in response to the application of T6085 and over time, using amplicon sequencing. Residues of the prior year’s wheat crop and the current year’s wheat spikes were collected at multiple time points, and kernel samples were collected at harvest. DNA was extracted from the collected wheat tissues, and amplicon sequencing was performed to profile microbiomes using 16S v4 rRNA amplicons for bacteria and ITS2 amplicons for fungi. Quantitative PCR was performed to evaluate the absolute abundances of F. graminearum and T. gamsii in different wheat tissues. Disease progression was tracked visually during the growing season, revealing that FHB severity and incidence were significantly reduced when T6085 was applied to wheat spikes at anthesis. However, treatment with T6085 did not lessen the F. graminearum abundance in wheat spikes or kernels. There were substantial changes in F. graminearum abundance over time; in crop residue, pathogen abundance was highest at the initial time point and declined over time, while in wheat spikes, pathogen abundance increased significantly over time. The predominant bacterial taxa in wheat spikes and kernels were Pseudomonas, Enterobacter, and Pantoea, while Alternaria and Fusarium were the dominant fungal groups. Although the microbiome structure changed substantially over time, there were no community-scale rearrangements due to the T6085 treatment. The work suggests several other taxa that could be explored as potential biocontrol agents to integrate with T6085 treatment. However, the timing and the type of T6085 application need to be improved to give more advantages for T6085 to colonize and reduce the F. graminearum inoculum in the field.
Liver-stage fate determination in Plasmodium vivax parasites: Characterization of schizont growth and hypnozoite fating from patient isolates
Authors: Vantaux Amélie , Péneau Julie , Cooper Caitlin A. , Kyle Dennis E. , Witkowski Benoit , Maher Steven P.
Published: September 2022

Plasmodium vivax, one species of parasite causing human malaria, forms a dormant liver stage, termed the hypnozoite, which activate weeks, months or years after the primary infection, causing relapse episodes. Relapses significantly contribute to the vivax malaria burden and are only killed with drugs of the 8-aminoquinoline class, which are contraindicated in many vulnerable populations. Development of new therapies targeting hypnozoites is hindered, in part, by the lack of robust methods to continuously culture and characterize this parasite. As a result, the determinants of relapse periodicity and the molecular processes that drive hypnozoite formation, persistence, and activation are largely unknown. While previous reports have described vastly different liver-stage growth metrics attributable to which hepatocyte donor lot is used to initiate culture, a comprehensive assessment of how different P. vivax patient isolates behave in the same lots at the same time is logistically challenging. Using our primary human hepatocyte-based P. vivax liver-stage culture platform, we aimed to simultaneously test the effects of how hepatocyte donor lot and P. vivax patient isolate influence the fate of sporozoites and growth of liver schizonts. We found that, while environmental factors such as hepatocyte donor lot can modulate hypnozoite formation rate, the P. vivax case is also an important determinant of the proportion of hypnozoites observed in culture. In addition, we found schizont growth to be mostly influenced by hepatocyte donor lot. These results suggest that, while host hepatocytes harbor characteristics making them more- or less-supportive of a quiescent versus growing intracellular parasite, sporozoite fating toward hypnozoites is isolate-specific. Future studies involving these host–parasite interactions, including characterization of individual P. vivax strains, should consider the impact of culture conditions on hypnozoite formation, in order to better understand this important part of the parasite’s lifecycle.
Investigating genetic diversity within the most abundant and prevalent non-pathogenic leaf-associated bacteria interacting with Arabidopsis thaliana in natural habitats
Authors: Ramírez-Sánchez Daniela , Gibelin-Viala Chrystel , Mayjonade Baptiste , Duflos Rémi , Belmonte Elodie , Pailler Vincent , Bartoli Claudia , Carrere Sébastien , Vailleau Fabienne , Roux Fabrice
Published: September 2022

Microbiota modulates plant health and appears as a promising lever to develop innovative, sustainable and eco-friendly agro-ecosystems. Key patterns of microbiota assemblages in plants have been revealed by an extensive number of studies based on taxonomic profiling by metabarcoding. However, understanding the functionality of microbiota is still in its infancy and relies on reductionist approaches primarily based on the establishment of representative microbial collections. In Arabidopsis thaliana, most of these microbial collections include one strain per OTU isolated from a limited number of habitats, thereby neglecting the ecological potential of genetic diversity within microbial species. With this study, we aimed at estimating the extent of genetic variation between strains within the most abundant and prevalent leaf-associated non-pathogenic bacterial species in A. thaliana located south-west of France. By combining a culture-based collection approach consisting of the isolation of more than 7,000 bacterial colonies with an informative-driven approach, we isolated 35 pure strains from eight non-pathogenic bacterial species. We detected significant intra-specific genetic variation at the genomic level and for growth rate in synthetic media. In addition, significant host genetic variation was detected in response to most bacterial strains in in vitro conditions, albeit dependent on the developmental stage at which plants were inoculated, with the presence of both negative and positive responses on plant growth. Our study provides new genetic and genomic resources for a better understanding of the plant-microbe ecological interactions at the microbiota level. We also highlight the need of considering genetic variation in both non-pathogenic bacterial species and A. thaliana to decipher the genetic and molecular mechanisms involved in the ecologically relevant dialog between hosts and leaf microbiota.
Mitochondrial membrane models built from native lipid extracts: Interfacial and transport properties
Authors: Schiaffarino Olivia , Valdivieso González David , García-Pérez Inés M. , Peñalva Daniel A. , Almendro-Vedia Víctor G. , Natale Paolo , López-Montero Iván
Published: September 2022

The mitochondrion is an essential organelle enclosed by two membranes whose functionalities depend on their very specific protein and lipid compositions. Proteins from the outer mitochondrial membrane (OMM) are specialized in mitochondrial dynamics and mitophagy, whereas proteins of the inner mitochondrial membrane (IMM) have dedicated functions in cellular respiration and apoptosis. As for lipids, the OMM is enriched in glycerophosphatidyl choline but cardiolipin is exclusively found within the IMM. Though the lipid topology and distribution of the OMM and IMM are known since more than four decades, little is known about the interfacial and dynamic properties of the IMM and OMM lipid extracts. Here we build monolayers, supported bilayers and giant unilamellar vesicles (GUVs) of native OMM and IMM lipids extracts from porcine heart. Additionally, we perform a comparative analysis on the interfacial, phase immiscibility and mechanical properties of both types of extract. Our results show that IMM lipids form more expanded and softer membranes than OMM lipids, allowing a better understanding of the physicochemical and biophysical properties of mitochondrial membranes.
The role of extracellular vesicle miRNAs and tRNAs in synovial fibroblast senescence
Authors: Wijesinghe Susanne N. , Anderson James , Brown Thomas J. , Nanus Dominika E. , Housmans Bas , Green Jonathan A. , Hackl Matthias , Choi Katie K. , Arkill Kenton P. , Welting Tim , James Victoria , Jones Simon W. , Peffers Mandy J.
Published: September 2022

Extracellular vesicles are mediators of intercellular communication with critical roles in cellular senescence and ageing. In arthritis, senescence is linked to the activation of a pro-inflammatory phenotype contributing to chronic arthritis pathogenesis. We hypothesised that senescent osteoarthritic synovial fibroblasts induce senescence and a pro-inflammatory phenotype in non-senescent osteoarthritic fibroblasts, mediated through extracellular vesicle cargo. Small RNA-sequencing and mass spectrometry proteomics were performed on extracellular vesicles isolated from the secretome of non-senescent and irradiation-induced senescent synovial fibroblasts. β-galactosidase staining confirmed senescence in SFs. RNA sequencing identified 17 differentially expressed miRNAs, 11 lncRNAs, 14 tRNAs and one snoRNA and, 21 differentially abundant proteins were identified by mass spectrometry. Bioinformatics analysis of miRNAs identified fibrosis, cell proliferation, autophagy, and cell cycle as significant pathways, tRNA analysis was enriched for signaling pathways including FGF, PI3K/AKT and MAPK, whilst protein analysis identified PAX3-FOXO1, MYC and TFGB1 as enriched upstream regulators involved in senescence and cell cycle arrest. Finally, treatment of non-senescent synovial fibroblasts with senescent extracellular vesicles confirmed the bystander effect, inducing senescence in non-senescent cells potentially through down regulation of NF-κβ and cAMP response element signaling pathways thus supporting our hypothesis. Understanding the exact composition of EV-derived small RNAs of senescent cells in this way will inform our understanding of their roles in inflammation, intercellular communication, and as active molecules in the senescence bystander effect.
Possible molecular basis of the biochemical effects of cysteine-derived persulfides
Authors: Cuevasanta Ernesto , Benchoam Dayana , Semelak Jonathan A. , Möller Matías N. , Zeida Ari , Trujillo Madia , Alvarez Beatriz , Estrin Darío A.
Published: September 2022

Persulfides (RSSH/RSS−) are species closely related to thiols (RSH/RS−) and hydrogen sulfide (H2S/HS−), and can be formed in biological systems in both low and high molecular weight cysteine-containing compounds. They are key intermediates in catabolic and biosynthetic processes, and have been proposed to participate in the transduction of hydrogen sulfide effects. Persulfides are acidic, more acidic than thiols, and the persulfide anions are expected to be the predominant species at neutral pH. The persulfide anion has high nucleophilicity, due in part to the alpha effect, i.e., the increased reactivity of a nucleophile when the neighboring atom has high electron density. In addition, persulfides have electrophilic character, a property that is absent in both thiols and hydrogen sulfide. In this article, the biochemistry of persulfides is described, and the possible ways in which the formation of a persulfide could impact on the properties of the biomolecule involved are discussed.
Optimization of a GC-MS method for the profiling of microbiota-dependent metabolites in blood samples: An application to type 2 diabetes and prediabetes
Authors: Mojsak Patrycja , Maliszewska Katarzyna , Klimaszewska Paulina , Miniewska Katarzyna , Godzien Joanna , Sieminska Julia , Kretowski Adam , Ciborowski Michal
Published: September 2022

Changes in serum or plasma metabolome may reflect gut microbiota dysbiosis, which is also known to occur in patients with prediabetes and type 2 diabetes (T2DM). Thus, developing a robust method for the analysis of microbiota-dependent metabolites (MDMs) is an important issue. Gas chromatography with mass spectrometry (GC–MS) is a powerful approach enabling detection of a wide range of MDMs in biofluid samples with good repeatability and reproducibility, but requires selection of a suitable solvents and conditions. For this reason, we conducted for the first time the study in which, we demonstrated an optimisation of samples preparation steps for the measurement of 75 MDMs in two matrices. Different solvents or mixtures of solvents for MDMs extraction, various concentrations and volumes of derivatizing reagents as well as temperature programs at methoxymation and silylation step, were tested. The stability, repeatability and reproducibility of the 75 MDMs measurement were assessed by determining the relative standard deviation (RSD). Finally, we used the developed method to analyse serum samples from 18 prediabetic (PreDiab group) and 24 T2DM patients (T2DM group) from our 1000PLUS cohort. The study groups were homogeneous and did not differ in age and body mass index. To select statistically significant metabolites, T2DM vs. PreDiab comparison was performed using multivariate statistics. Our experiment revealed changes in 18 MDMs belonging to different classes of compounds, and seven of them, based on the SVM classification model, were selected as a panel of potential biomarkers, able to distinguish between patients with T2DM and prediabetes.
Alpha3/alpha2 power ratios relate to performance on a virtual reality shopping task in ageing adults
Authors: Patchitt Joel , Porffy Lilla A. , Whomersley Gabriella , Szentgyorgyi Timea , Brett Jack , Mouchlianitis Elias , Mehta Mitul A. , Nottage Judith F. , Shergill Sukhi S.
Published: September 2022

Background

Aspects of cognitive function decline with age. This phenomenon is referred to as age-related cognitive decline (ARCD). Improving the understanding of these changes that occur as part of the ageing process can serve to enhance the detection of the more incapacitating neurodegenerative disorders such as Alzheimer’s disease (AD). In this study, we employ novel methods to assess ARCD by exploring the utility of the alpha3/alpha2 electroencephalogram (EEG) power ratio – a marker of AD, and a novel virtual reality (VR) functional cognition task – VStore, in discriminating between young and ageing healthy adults.

Materials and methods

Twenty young individuals aged 20–30, and 20 older adults aged 60–70 took part in the study. Participants underwent resting-state EEG and completed VStore and the Cogstate Computerised Cognitive Battery. The difference in alpha3/alpha2 power ratios between the age groups was tested using t-test. In addition, the discriminatory accuracy of VStore and Cogstate were compared using logistic regression and overlying receiver operating characteristic (ROC) curves. Youden’s J statistic was used to establish the optimal threshold for sensitivity and specificity and model performance was evaluated with the DeLong’s test. Finally, alpha3/alpha2 power ratios were correlated with VStote and Cogstate performance.

Results

The difference in alpha3/alpha2 power ratios between age cohorts was not statistically significant. On the other hand, VStore discriminated between age groups with high sensitivity (94%) and specificity (95%) The Cogstate Pre-clinical Alzheimer’s Battery achieved a sensitivity of 89% and specificity of 60%, and Cogstate Composite Score achieved a sensitivity of 83% and specificity of 85%. The differences between the discriminatory accuracy of VStore and Cogstate models were statistically significant. Finally, high alpha3/alpha2 power ratios correlated strongly with VStore (r = 0.73), the Cogstate Pre-clinical Alzheimer’s Battery (r = -0.67), and Cogstate Composite Score (r = -0.76).

Conclusion

While we did not find evidence that the alpha3/alpha2 power ratio is elevated in healthy ageing individuals compared to young individuals, we demonstrated that VStore can classify age cohorts with high accuracy, supporting its utility in the assessment of ARCD. In addition, we found preliminary evidence that elevated alpha3/alpha2 power ratio may be linked to lower cognitive performance.
The functional connectivity of language network across the life span: Disentangling the effects of typical aging from Alzheimer’s disease
Authors: Rafiq Marie , Jucla Mélanie , Guerrier Laura , Péran Patrice , Pariente Jérémie , Pistono Aurélie
Published: September 2022

Language is usually characterized as the most preserved cognitive function during typical aging. Several neuroimaging studies have shown that healthy aging is characterized by inter-network compensation which correlates with better language performance. On the contrary, language deficits occur early in the course of Alzheimer’s disease (AD). Therefore, this study compares young participants, healthy older participants, and prodromal AD participants, to characterize functional connectivity changes in language due to healthy aging or prodromal AD. We first compared measures of integrated local correlations (ILCs) and fractional amplitude of low-frequency oscillations (fALFFs) in language areas. We showed that both groups of older adults had lower connectivity values within frontal language-related areas. In the healthy older group, higher integrated local correlation (ILC) and fALFF values in frontal areas were positively correlated with fluency and naming tasks. We then performed seed-based analyses for more precise discrimination between healthy aging and prodromal AD. Healthy older adults showed no functional alterations at a seed-based level when the seed area was not or only slightly impaired compared to the young adults [i.e., inferior frontal gyrus (IFG)], while prodromal AD participants also showed decreased connectivity at a seed-based level. On the contrary, when the seed area was similarly impaired in healthy older adults and prodromal AD participants on ILC and fALFF measures, their connectivity maps were also similar during seed-to-voxel analyses [i.e., superior frontal gyrus (SFG)]. Current results show that functional connectivity measures at a voxel level (ILC and fALFF) are already impacted in healthy aging. These findings imply that the functional compensations observed in healthy aging depend on the functional integrity of brain areas at a voxel level.
EEG brain oscillations are modulated by interoception in response to a synchronized motor vs. cognitive task
Authors: Angioletti Laura , Balconi Michela
Published: September 2022

So far, little is known about how conscious attention to internal body signals, that is, interoception, affects the synchronization with another person, a necessary or required social process that promotes affiliations and cooperation during daily joint social interactions. The effect of explicit interoceptive attentiveness (IA) modulation, conceived as the focus on the breath for a given time interval, on electrophysiological (EEG) correlates during an interpersonal motor task compared with a cognitive synchronization task was investigated in this study. A total of 28 healthy participants performed a motor and a cognitive synchronization task during the focus and no-focus breath conditions. During the tasks, frequency bands (delta, theta, alpha, and beta bands) from the frontal, temporo-central, and parieto-occipital regions of interest (ROIs) were acquired. According to the results, significantly higher delta and theta power were found in the focus condition in the frontal ROI during the execution of the motor than the cognitive synchronization task. Moreover, in the same experimental condition, delta and beta band power increased in the temporo-central ROI. The current study suggested two main patterns of frequency band modulation during the execution of a motor compared with the cognitive synchronization task while a person is focusing the attention on one's breath. This study can be considered as the first attempt to classify the different effects of interoceptive manipulation on motor and cognitive synchronization tasks using neurophysiological measures.
The retina of the lab rat: focus on retinal ganglion cells and photoreceptors
Authors: Galindo-Romero Caridad , Norte-Muñoz María , Gallego-Ortega Alejandro , Rodríguez-Ramírez Kristy T. , Lucas-Ruiz Fernando , González-Riquelme María Josefa , Vidal-Sanz Manuel , Agudo-Barriuso Marta
Published: September 2022

Albino and pigmented rat strains are widely used in models to study retinal degeneration and to test new therapies. Here, we have summarized the main topographical and functional characteristics of the rat retina focussing on photoreceptors and retinal ganglion cells (RGCs), the beginning and end of the retinal circuitry, respectively. These neurons are very sensitive to injury and disease, and thus knowing their normal number, topography, and function is essential to accurately investigate on neuronal survival and protection.
Correlation Among Psychological Resilience, Social Support, and Coping Style in Patients With Complicated Hepatolithiasis
Authors: Wang Ying , Huang Chunqiu , Zhang Honghui , Cai Yimin , Shen Zhoumin , Hu Xiahong , Zhou Bifang , Yang Lifen , Chen Qian
Published: September 2022

Objectives: To investigate the correlation between psychological resilience, social support, and coping styles in patients with complicated hepatolithiasis.

Methods: The objective sampling method was used in this study to select a total of 156 patients with complicated hepatolithiasis in a Third-class Grade A hospital in Changsha, Hunan Province from January to December 2019. Self-designed general data questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), the Social Support Rating Scale (SSRS), and the Simplified Coping Style Questionnaire (SCSQ) were used to conduct a questionnaire investigation. Spearman correlation analysis was used to analyze the correlation between psychological resilience, social support, and coping styles in patients with complicated hepatolithiasis.

Results: Both the total score of psychological resilience (45.79 ± 16.28) and social support (35.71 ± 9.92) of patients with complicated hepatolithiasis were significantly lower than those of the domestic norm. The total score of psychological resilience of patients with complicated hepatolithiasis was positively correlated with the total score of social support (r = 0.570, p < 0.01). The total score of psychological resilience and its three dimensions were positively correlated with the positive coping (r = 0.682, 0.673, 0.663, 0.535, p < 0.01)and negatively correlated with negative coping (r = −0.240, −0.207, −0.221, −0.286, p < 0.01).

Conclusions: This study indicated that strengthening social support and improving the coping style of patients with complicated hepatolithiasis are helpful to improve their psychological resilience, which provided theory basis and reference for further intervention measures to improve social support system and coping styles.
Prenatal maternal stress and offspring aggressive behavior: Intergenerational and transgenerational inheritance
Authors: Mbiydzenyuy Ngala Elvis , Hemmings Sian Megan Joanna , Qulu Lihle
Published: September 2022

Even though studies have shown that prenatal maternal stress is associated with increased reactivity of the HPA axis, the association between prenatal maternal stress and fetal glucocorticoid exposure is complex and most likely dependent on unidentified and poorly understood variables including nature and timing of prenatal insults. The precise mechanisms in which prenatal maternal stress influence neuroendocrine signaling between the maternal-placental-fetal interface are still unclear. The aim of this review article is to bring comprehensive basic concepts about prenatal maternal stress and mechanisms of transmission of maternal stress to the fetus. This review covers recent studies showing associations between maternal stress and alterations in offspring aggressive behavior, as well as the possible pathways for the “transmission” of maternal stress to the fetus: (1) maternal-fetal HPA axis dysregulation; (2) intrauterine environment disruption due to variations in uterine artery flow; (3) epigenetic modifications of genes implicated in aggressive behavior. Here, we present evidence for the phenomenon of intergenerational and transgenerational transmission, to better understands the mechanism(s) of transmission from parent to offspring. We discuss studies showing associations between maternal stress and alterations in offspring taking note of neuroendocrine, brain architecture and epigenetic changes that may suggest risk for aggressive behavior. We highlight animal and human studies that focus on intergenerational transmission following exposure to stress from a biological mechanistic point of view, and maternal stress-induced epigenetic modifications that have potential to impact on aggressive behavior in later generations.
A scalable assay for chemical preference of small freshwater fish
Authors: Gallois Benjamin , Pontani Lea-Laetita , Debrégeas Georges , Candelier Raphaël
Published: September 2022

Sensing the chemical world is of primary importance for aquatic organisms, and small freshwater fish are increasingly used in toxicology, ethology, and neuroscience by virtue of their ease of manipulation, tissue imaging amenability, and genetic tractability. However, precise behavioral analyses are generally challenging to perform due to the lack of knowledge of what chemical the fish are exposed to at any given moment. Here we developed a behavioral assay and a specific infrared dye to probe the preference of young zebrafish for virtually any compound. We found that the innate aversion of zebrafish to citric acid is not mediated by modulation of the swim but rather by immediate avoidance reactions when the product is sensed and that the preference of juvenile zebrafish for ATP changes from repulsion to attraction during successive exposures. We propose an information-based behavioral model for which an exploration index emerges as a relevant behavioral descriptor, complementary to the standard preference index. Our setup features a high versatility in protocols and is automatic and scalable, which paves the way for high-throughput preference compound screening at different ages.
A novel activation function based recurrent neural networks and their applications on sentiment classification and dynamic problems solving
Authors: Zhu Qingyi , Tan Mingtao
Published: September 2022

In this paper, a nonlinear activation function (NAF) is proposed to constructed three recurrent neural network (RNN) models (Simple RNN (SRNN) model, Long Short-term Memory (LSTM) model and Gated Recurrent Unit (GRU) model) for sentiment classification. The Internet Movie Database (IMDB) sentiment classification experiment results demonstrate that the three RNN models using the NAF achieve better accuracy and lower loss values compared with other commonly used activation functions (AF), such as ReLU, SELU etc. Moreover, in terms of dynamic problems solving, a fixed-time convergent recurrent neural network (FTCRNN) model with the NAF is constructed. Additionally, the fixed-time convergence property of the FTCRNN model is strictly validated and the upper bound convergence time formula of the FTCRNN model is obtained. Furthermore, the numerical simulation results of dynamic Sylvester equation (DSE) solving using the FTCRNN model indicate that the neural state solutions of the FTCRNN model quickly converge to the theoretical solutions of DSE problems whether there are noises or not. Ultimately, the FTCRNN model is also utilized to realize trajectory tracking of robot manipulator and electric circuit currents computation for the further validation of its accurateness and robustness, and the corresponding results further validate its superior performance and widespread applicability.
Conditional deletion of MAD2B in forebrain neurons enhances hippocampus-dependent learning and memory in mice
Authors: Cheng Li , Su Yanfang , Zhi Kaining , Xie Yaru , Zhang Chun , Meng Xianfang
Published: September 2022

Mitotic arrest deficient 2-like protein 2 (MAD2B) is not only a DNA damage repair agent but also a cell cycle regulator that is widely expressed in the hippocampus and the cerebral cortex. However, the functions of MAD2B in hippocampal and cerebral cortical neurons are poorly understood. In this study, we crossed MAD2Bflox/flox and calcium/calmodulin-dependent protein kinase II alpha (Camk2a)-Cre mice to conditionally knock out MAD2B in the forebrain pyramidal neurons by the Cre/loxP recombinase system. First, RNA sequencing suggested that the differentially expressed genes in the hippocampus and the cerebral cortex between the WT and the MAD2B cKO mice were related to learning and memory. Then, the results of behavioral tests, including the Morris water maze test, the novel object recognition test, and the contextual fear conditioning experiment, suggested that the learning and memory abilities of the MAD2B cKO mice had improved. Moreover, conditional knockout of MAD2B increased the number of neurons without affecting the number of glial cells in the hippocampal CA1 and the cerebral cortex. At the same time, the number of doublecortin-positive (DCX+) cells was increased in the dentate gyrus (DG) of the MAD2B cKO mice. In addition, as shown by Golgi staining, the MAD2B cKO mice had more mushroom-like and long-like spines than the WT mice. Transmission electron microscopy (TEM) revealed that spine synapses increased and shaft synapses decreased in the CA1 of the MAD2B cKO mice. Taken together, our findings indicated that MAD2B plays an essential role in regulating learning and memory.
Intrinsically photosensitive retinal ganglion cells in glaucoma
Authors: Gao Jingyi , Provencio Ignacio , Liu Xiaorong
Published: September 2022

Glaucoma is a group of eye diseases afflicting more than 70 million people worldwide. It is characterized by damage to retinal ganglion cells (RGCs) that ultimately leads to the death of the cells and vision loss. The diversity of RGC types has been appreciated for decades, and studies, including ours, have shown that RGCs degenerate and die in a type-specific manner in rodent models of glaucoma. The type-specific loss of RGCs results in differential damage to visual and non-visual functions. One type of RGC, the intrinsically photosensitive retinal ganglion cell (ipRGC), expressing the photopigment melanopsin, serves a broad array of non-visual responses to light. Since its discovery, six subtypes of ipRGC have been described, each contributing to various image-forming and non-image-forming functions such as circadian photoentrainment, the pupillary light reflex, the photic control of mood and sleep, and visual contrast sensitivity. We recently demonstrated a link between type-specific ipRGC survival and behavioral deficits in a mouse model of chronic ocular hypertension. This review focuses on the type-specific ipRGC degeneration and associated behavioral changes in animal models and glaucoma patients. A better understanding of how glaucomatous insult impacts the ipRGC-based circuits will have broad impacts on improving the treatment of glaucoma-associated non-visual disorders.
An implantable neurophysiology platform: Broadening research capabilities in free-living and non-traditional animals
Authors: Gaidica Matt , Dantzer Ben
Published: September 2022

Animal-borne sensors that can record and transmit data (“biologgers”) are becoming smaller and more capable at a rapid pace. Biologgers have provided enormous insight into the covert lives of many free-ranging animals by characterizing behavioral motifs, estimating energy expenditure, and tracking movement over vast distances, thereby serving both scientific and conservational endpoints. However, given that biologgers are usually attached externally, access to the brain and neurophysiological data has been largely unexplored outside of the laboratory, limiting our understanding of how the brain adapts to, interacts with, or addresses challenges of the natural world. For example, there are only a handful of studies in free-living animals examining the role of sleep, resulting in a wake-centric view of behavior despite the fact that sleep often encompasses a large portion of an animal’s day and plays a vital role in maintaining homeostasis. The growing need to understand sleep from a mechanistic viewpoint and probe its function led us to design an implantable neurophysiology platform that can record brain activity and inertial data, while utilizing a wireless link to enable a suite of forward-looking capabilities. Here, we describe our design approach and demonstrate our device’s capability in a standard laboratory rat as well as a captive fox squirrel. We also discuss the methodological and ethical implications of deploying this new class of device “into the wild” to fill outstanding knowledge gaps.
Neural mechanisms for turn-taking in duetting plain-tailed wrens
Authors: Coleman Melissa J. , Day Nancy F. , Fortune Eric S.
Published: September 2022

Recent studies conducted in the natural habitats of songbirds have provided new insights into the neural mechanisms of turn–taking. For example, female and male plain–tailed wrens (Pheugopedius euophrys) sing a duet that is so precisely timed it sounds as if a single bird is singing. In this review, we discuss our studies examining the sensory and motor cues that pairs of wrens use to coordinate the rapid alternation of syllable production. Our studies included behavioral measurements of freely–behaving wrens in their natural habitat and neurophysiological experiments conducted in awake and anesthetized individuals at field sites in Ecuador. These studies show that each partner has a pattern-generating circuit in their brain that is linked via acoustic feedback between individuals. A similar control strategy has been described in another species of duetting songbird, white–browed sparrow–weavers (Plocepasser mahali). Interestingly, the combination of neurophysiological results from urethane-anesthetized and awake wrens suggest a role for inhibition in coordinating the timing of turn–taking. Finally, we highlight some of the unique challenges of conducting these experiments at remote field sites.
High-Risk Intracranial Atherosclerotic Stenosis Despite Aggressive Medical Treatment: Protocol for a Prospective Nested Case-Control Study
Authors: Wang Tao , Luo Jichang , Liu Changyi , Yang Bin , Xu Ran , Li Long , Yang Kun , Zhang Chao , Wang Yabing , Chen Yanfei , Gao Peng , Chen Jian , Jiao Liqun , Ma Yan
Published: September 2022

Introduction

Intracranial atherosclerotic disease (ICAD) is one of the most important etiologies of ischemic stroke, especially in Asia. Although medical treatment was recommended as the first-line therapy for ICAD, the recurrent stroke rate was still high in severe stenosis of ICAD despite aggressive medical treatment. Traditionally, the degree of luminal stenosis is used as the principal index for stroke risk stratification in patients with ICAD, while recent evidence suggested that symptomatic atherosclerotic plaques were characterized by plaque features and hemodynamics. This prospective, longitudinal, and nested case-control study aims to identify multimodal imaging predictors of high-risk patients with ICAD refractory to medical treatment and explore a refined risk stratification model based on the above multimodal imaging predictors.

Methods

This prospective, longitudinal, and nested case-control study includes 400 symptomatic patients with ICAD with 50–99% of stenosis treated with aggressive medical therapy. All patients who meet the eligibility criteria are assessed by multimodal imaging examination from three aspects, including lumen stenosis, plaque characteristics, and hemodynamic features. The enrolled patients receive aggressive medical management, including antiplatelet therapy and cardiovascular risk control. The primary outcome is ischemic stroke or death attributable to the lesion of the target vessel within 1 year. The secondary endpoints are (1) any stroke or death; (2) all-cause mortality; (3) any stroke out of the territory of the responsible lesion; (4) functional outcome with the modified Rankin Scale (mRS).

Ethics and Dissemination

This study has been approved by the ethics committee of our center ([2021]083) and has been prospectively registered (Registration No: ChiCTR2100048832). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings.
The dual function of microglial polarization and its treatment targets in ischemic stroke
Authors: Mo Yong , Xu Weilin , Fu Kaijing , Chen Hainan , Wen Jing , Huang Qianrong , Guo Fangzhou , Mo Ligen , Yan Jun
Published: September 2022

Stroke is the leading cause of disability and death worldwide, with ischemic stroke occurring in ~5% of the global population every year. Recently, many studies have been conducted on the inflammatory response after stroke. Microglial/macrophage polarization has a dual function and is critical to the pathology of ischemic stroke. Microglial/macrophage activation is important in reducing neuronal apoptosis, enhancing neurogenesis, and promoting functional recovery after ischemic stroke. In this review, we investigate the physiological characteristics and functions of microglia in the brain, the activation and phenotypic polarization of microglia and macrophages after stroke, the signaling mechanisms of polarization states, and the contribution of microglia to brain pathology and repair. We summarize recent advances in stroke-related microglia research, highlighting breakthroughs in therapeutic strategies for microglial responses after stroke, thereby providing new ideas for the treatment of ischemic stroke.
Automatic segmentation of the core of the acoustic radiation in humans
Authors: Siegbahn Malin , Engmér Berglin Cecilia , Moreno Rodrigo
Published: September 2022

Introduction

Acoustic radiation is one of the most important white matter fiber bundles of the human auditory system. However, segmenting the acoustic radiation is challenging due to its small size and proximity to several larger fiber bundles. TractSeg is a method that uses a neural network to segment some of the major fiber bundles in the brain. This study aims to train TractSeg to segment the core of acoustic radiation.

Methods

We propose a methodology to automatically extract the acoustic radiation from human connectome data, which is both of high quality and high resolution. The segmentation masks generated by TractSeg of nearby fiber bundles are used to steer the generation of valid streamlines through tractography. Only streamlines connecting the Heschl's gyrus and the medial geniculate nucleus were considered. These streamlines are then used to create masks of the core of the acoustic radiation that is used to train the neural network of TractSeg. The trained network is used to automatically segment the acoustic radiation from unseen images.

Results

The trained neural network successfully extracted anatomically plausible masks of the core of the acoustic radiation in human connectome data. We also applied the method to a dataset of 17 patients with unilateral congenital ear canal atresia and 17 age- and gender-paired controls acquired in a clinical setting. The method was able to extract 53/68 acoustic radiation in the dataset acquired with clinical settings. In 14/68 cases, the method generated fragments of the acoustic radiation and completely failed in a single case. The performance of the method on patients and controls was similar.

Discussion

In most cases, it is possible to segment the core of the acoustic radiations even in images acquired with clinical settings in a few seconds using a pre-trained neural network.
Complexity changes in functional state dynamics suggest focal connectivity reductions
Authors: Blair David Sutherland , Soriano-Mas Carles , Cabral Joana , Moreira Pedro , Morgado Pedro , Deco Gustavo
Published: September 2022

The past two decades have seen an explosion in the methods and directions of neuroscience research. Along with many others, complexity research has rapidly gained traction as both an independent research field and a valuable subdiscipline in computational neuroscience. In the past decade alone, several studies have suggested that psychiatric disorders affect the spatiotemporal complexity of both global and region-specific brain activity (Liu et al., 2013;Adhikari et al., 2017;Li et al., 2018). However, many of these studies have not accounted for the distributed nature of cognition in either the global or regional complexity estimates, which may lead to erroneous interpretations of both global and region-specific entropy estimates. To alleviate this concern, we propose a novel method for estimating complexity. This method relies upon projecting dynamic functional connectivity into a low-dimensional space which captures the distributed nature of brain activity. Dimension-specific entropy may be estimated within this space, which in turn allows for a rapid estimate of global signal complexity. Testing this method on a recently acquired obsessive-compulsive disorder dataset reveals substantial increases in the complexity of both global and dimension-specific activity versus healthy controls, suggesting that obsessive-compulsive patients may experience increased disorder in cognition. To probe the potential causes of this alteration, we estimate subject-level effective connectivityviaa Hopf oscillator-based model dynamic model, the results of which suggest that obsessive-compulsive patients may experience abnormally high connectivity across a broad network in the cortex. These findings are broadly in line with results from previous studies, suggesting that this method is both robust and sensitive to group-level complexity alterations.
Development of a wireless ultrasonic brain stimulation system for concurrent bilateral neuromodulation in freely moving rodents
Authors: Kim Evgenii , Kum Jeungeun , Lee Seung Hyun , Kim Hyungmin
Published: September 2022

Bilateral brain stimulation is an important modality used to investigate brain circuits and treat neurological conditions. Recently, low-intensity pulsed ultrasound (LIPUS) received significant attention as a novel non-invasive neurostimulation technique with high spatial specificity. Despite the growing interest, the typical ultrasound brain stimulation study, especially for small animals, is limited to a single target of sonication. The constraint is associated with the complexity and the cost of the hardware system required to achieve multi-regional sonication. This work presented the development of a low-cost LIPUS system with a pair of single-element ultrasound transducers to address the above problem. The system was built with a multicore processor with an RF amplifier circuit. In addition, LIPUS device was incorporated with a wireless module (bluetooth low energy) and powered by a single 3.7 V battery. As a result, we achieved an ultrasound transmission with a central frequency of 380 kHz and a peak-to-peak pressure of 480 kPa from each ultrasound transducer. The developed system was further applied to anesthetized rats to investigate the difference between uni- and bilateral stimulation. A significant difference in cortical power density extracted from electroencephalogram signals was observed between uni- and bilateral LIPUS stimulation. The developed device provides an affordable solution to investigate the effects of LIPUS on functional interhemispheric connection.
Developmental or adult-onset deletion of neurotensin receptor-1 from dopamine neurons differentially reduces body weight
Authors: Perez-Bonilla Patricia , Ramirez-Virella Jariel , Menon Pooja , Troyano-Rodriguez Eva , Arriaga Sydney K. , Makela Anna , Bugescu Raluca , Beckstead Michael J. , Leinninger Gina M.
Published: September 2022

Central neurotensin signaling via neurotensin receptor-1 (NtsR1) modulates various aspects of physiology, including suppressing feeding and promoting locomotor activity that can support weight loss. However, it remains unclear when and where NtsR1 expression contributes to control of body weight vs. other effects. We previously showed that activating ventral tegmental area (VTA) dopamine (DA) neurons that express NtsR1 promotes weight loss. We therefore hypothesized that deleting NtsR1 from DA neurons would promote weight gain by increasing food intake and decreasing physical activity. In contrast, developmental deletion of NtsR1 from DA neurons (by crossing DATCre mice with NtsR1flox/flox mice) had no impact on the feeding or body weight of mice fed a chow diet, though it augmented locomotor activity. Developmental deletion of NtsR1 from DA neurons protected mice from diet-induced obesity, but not via altering feeding, physical activity, or energy expenditure. Given that NtsR1 may exert distinct roles within development vs. adulthood, we then examined the impact of adult-onset deletion of NtsR1 from VTA DA neurons. We injected adult NtsR1flox/flox mice in the VTA with adeno associated virus to Cre-dependently delete NtsR1 in the VTA (VTAR1Null mice) and compared them to mice with intact NtsR1 (Controls). Again, in contrast to our hypothesis, VTAR1Null mice gained less weight than Controls while on normal chow or high fat diets. Moreover, VTAR1Null mice exhibited blunted feeding after fasting, suggesting a role for NtsR1 in adult VTA DA neurons in coordinating energy need and intake. Altogether, these data suggest that intact expression of NtsR1 in DA neurons is necessary for appropriate regulation of body weight, but a lack of NtsR1 in the developing vs. adult DA system protects from weight gain via different mechanisms. These findings emphasize the need for temporal and site-specific resolution to fully understand the role of NtsR1 within the brain.