bluuebunny/crossref_metadata_2025 huggingface dataset:
The Molecular Basis of the Effect of Temperature on the Structure and Function of SARS-CoV-2 Spike Protein
Authors: Khan Faez Iqbal , Lobb Kevin A. , Lai Dakun
Published: March 2022

The remarkable rise of the current COVID-19 pandemic to every part of the globe has raised key concerns for the current public healthcare system. The spike (S) protein of SARS-CoV-2 shows an important part in the cell membrane fusion and receptor recognition. It is a key target for vaccine production. Several researchers studied the nature of this protein under various environmental conditions. In this work, we applied molecular modeling and extensive molecular dynamics simulation approaches at 0°C (273.15 K), 20°C (293.15 K), 40°C (313.15 K), and 60°C (333.15 K) to study the detailed conformational alterations in the SARS-CoV-2 S protein. Our aim is to understand the influence of temperatures on the structure, function, and dynamics of the S protein of SARS-CoV-2. The structural deviations, and atomic and residual fluctuations were least at low (0°C) and high (60°C) temperature. Even the internal residues of the SARS-CoV-2 S protein are not accessible to solvent at high temperature. Furthermore, there was no unfolding of SARS-CoV-2 spike S reported at higher temperature. The most stable conformations of the SARS-CoV-2 S protein were reported at 20°C, but the free energy minimum region of the SARS-CoV-2 S protein was sharper at 40°C than other temperatures. Our findings revealed that higher temperatures have little or no influence on the stability and folding of the SARS-CoV-2 S protein.
Where to From Here?
Authors: Schleif Robert , Espinosa Manuel
Published: March 2022

The biological-biochemical community has been shocked and delighted by the remarkable progress that has recently been made on a problem that has consumed the attention, energy, and resources of many, if not most of the scientists in the field for the past 50 years. The problem has been to predict the tertiary structure of a protein merely from its amino acid sequence. Nature does it easily enough, but it has been an incredibly difficult problem, often considered intractable, for humankind. The breakthrough has come in the form of two computer-based approaches, AlphaFold2 and RoseTTAFold in conjunction with factors such as the use of vast computing power, the field of artificial intelligence, and the existence of huge protein sequence databases. The advancement of these tools depended upon and was stimulated by the last 50 years of development of smaller and smaller and more and more powerful electronics components, mainly processors and memory. Along with the problem of protein folding, determining the function or mechanism of action of proteins has similarly limped along as did protein folding until the recent breakthroughs. Perhaps AlphaFold2 and RoseTTAFold can substantially aid in protein mechanistic studies. Now it is not completely insane to consider what might be the next grand challenge in biochemistry-biology. We offer several possibilities.
Sharpening Working Memory With Real-Time Electrophysiological Brain Signals: Which Neurofeedback Paradigms Work?
Authors: Jiang Yang , Jessee William , Hoyng Stevie , Borhani Soheil , Liu Ziming , Zhao Xiaopeng , Price Lacey K. , High Walter , Suhl Jeremiah , Cerel-Suhl Sylvia
Published: March 2022

Growing evidence supports the idea that the ultimate biofeedback is to reward sensory pleasure (e.g., enhanced visual clarity) in real-time to neural circuits that are associated with a desired performance, such as excellent memory retrieval. Neurofeedback is biofeedback that uses real-time sensory reward to brain activity associated with a certain performance (e.g., accurate and fast recall). Working memory is a key component of human intelligence. The challenges are in our current limited understanding of neurocognitive dysfunctions as well as in technical difficulties for closed-loop feedback in true real-time. Here we review recent advancements of real time neurofeedback to improve memory training in healthy young and older adults. With new advancements in neuromarkers of specific neurophysiological functions, neurofeedback training should be better targeted beyond a single frequency approach to include frequency interactions and event-related potentials. Our review confirms the positive trend that neurofeedback training mostly works to improve memory and cognition to some extent in most studies. Yet, the training typically takes multiple weeks with 2–3 sessions per week. We review various neurofeedback reward strategies and outcome measures. A well-known issue in such training is that some people simply do not respond to neurofeedback. Thus, we also review the literature of individual differences in psychological factors e.g., placebo effects and so-called “BCI illiteracy” (Brain Computer Interface illiteracy). We recommend the use of Neural modulation sensitivity or BCI insensitivity in the neurofeedback literature. Future directions include much needed research in mild cognitive impairment, in non-Alzheimer’s dementia populations, and neurofeedback using EEG features during resting and sleep for memory enhancement and as sensitive outcome measures.
Age-Related Hearing Loss Is Accompanied by Chronic Inflammation in the Cochlea and the Cochlear Nucleus
Authors: Seicol Benjamin J. , Lin Shengyin , Xie Ruili
Published: March 2022

Age-related hearing loss (ARHL) is a major hearing impairment characterized by pathological changes in both the peripheral and central auditory systems. Low-grade inflammation was observed in the cochlea of deceased human subjects with ARHL and animal models of early onset ARHL, which suggests that inflammation contributes to the development of ARHL. However, it remains elusive how chronic inflammation progresses during normal aging in the cochlea, and especially the accompanying changes of neuroinflammation in the central auditory system. To address this, we investigated chronic inflammation in both the cochlea and the cochlear nucleus (CN) of CBA/CaJ mice, an inbred mouse strain that undergoes normal aging and develops human, like-late-onset ARHL. Using immunohistochemistry, confocal microscopy, and quantitative image processing, we measured the accumulation and activation of macrophages in the cochlea and microglia in the CN using their shared markers: ionized calcium binding adaptor molecule 1 (Iba1) and CD68—a marker of phagocytic activity. We found progressive increases in the area covered by Iba1-labeled macrophages and enhanced CD68 staining in the osseous spiral lamina of the cochlea that correlated with elevated ABR threshold across the lifespan. During the process, we further identified significant increases in microglial activation and C1q deposition in the CN, indicating increased neuroinflammation and complement activation in the central auditory system. Our study suggests that during normal aging, chronic inflammation occurs in both the peripheral and the central auditory system, which may contribute in coordination to the development of ARHL.
Schizophrenia-Mimicking Layers Outperform Conventional Neural Network Layers
Authors: Mizutani Ryuta , Noguchi Senta , Saiga Rino , Yamashita Yuichi , Miyashita Mitsuhiro , Arai Makoto , Itokawa Masanari
Published: March 2022

We have reported nanometer-scale three-dimensional studies of brain networks of schizophrenia cases and found that their neurites are thin and tortuous when compared to healthy controls. This suggests that connections between distal neurons are suppressed in microcircuits of schizophrenia cases. In this study, we applied these biological findings to the design of a schizophrenia-mimicking artificial neural network to simulate the observed connection alteration in the disorder. Neural networks that have a “schizophrenia connection layer” in place of a fully connected layer were subjected to image classification tasks using the MNIST and CIFAR-10 datasets. The results revealed that the schizophrenia connection layer is tolerant to overfitting and outperforms a fully connected layer. The outperformance was observed only for networks using band matrices as weight windows, indicating that the shape of the weight matrix is relevant to the network performance. A schizophrenia convolution layer was also tested using the VGG configuration, showing that 60% of the kernel weights of the last three convolution layers can be eliminated without loss of accuracy. The schizophrenia layers can be used instead of conventional layers without any change in the network configuration and training procedures; hence, neural networks can easily take advantage of these layers. The results of this study suggest that the connection alteration found in schizophrenia is not a burden to the brain, but has functional roles in brain performance.
Generative Adversarial Training for Supervised and Semi-supervised Learning
Authors: Wang Xianmin , Li Jing , Liu Qi , Zhao Wenpeng , Li Zuoyong , Wang Wenhao
Published: March 2022

Neural networks have played critical roles in many research fields. The recently proposed adversarial training (AT) can improve the generalization ability of neural networks by adding intentional perturbations in the training process, but sometimes still fail to generate worst-case perturbations, thus resulting in limited improvement. Instead of designing a specific smoothness function and seeking an approximate solution used in existing AT methods, we propose a new training methodology, named Generative AT (GAT) in this article, for supervised and semi-supervised learning. The key idea of GAT is to formulate the learning task as a minimax game, in which the perturbation generator aims to yield the worst-case perturbations that maximize the deviation of output distribution, while the target classifier is to minimize the impact of this perturbation and prediction error. To solve this minimax optimization problem, a new adversarial loss function is constructed based on the cross-entropy measure. As a result, the smoothness and confidence of the model are both greatly improved. Moreover, we develop a trajectory-preserving-based alternating update strategy to enable the stable training of GAT. Numerous experiments conducted on benchmark datasets clearly demonstrate that the proposed GAT significantly outperforms the state-of-the-art AT methods in terms of supervised and semi-supervised learning tasks, especially when the number of labeled examples is rather small in semi-supervised learning.
Quantifying Glial-Glial Tiling Using Automated Image Analysis in Drosophila
Authors: Salazar Gabriela , Ross Grace , Maserejian Ariana E. , Coutinho-Budd Jaeda
Published: March 2022

Not only do glia form close associations with neurons throughout the central nervous system (CNS), but glial cells also interact closely with other glial cells. As these cells mature, they undergo a phenomenon known as glial tiling, where they grow to abut one another, often without invading each other’s boundaries. Glial tiling occurs throughout the animal kingdom, from fruit flies to humans; however, not much is known about the glial-glial interactions that lead to and maintain this tiling. Drosophila provide a strong model to investigate glial-glial tiling, where tiling occurs both among individual glial cells of the same subtype, as well as between those of different subtypes. Furthermore, the spatial segregation of the CNS allows for the unique ability to visualize and manipulate inter-subtype interactions. Previous work in Drosophila has suggested an interaction between cortex glia and astrocytes, where astrocytes cross the normal neuropil-cortex boundary in response to dysfunctional cortex glia. Here, we further explore this interaction by implementing an automated pipeline to more fully characterize this astrocyte-cortex glial relationship. By quantifying and correlating the extent of cortex glial dysfunction and aberrant astrocyte infiltration using automated analysis, we maximize the size of the quantified dataset to reveal subtle patterns in astrocyte-cortex glial interactions. We provide a guide for creating and validating a fully-automated image analysis pipeline for exploring these interactions, and implement this pipeline to describe a significant correlation between cortex glial dysfunction and aberrant astrocyte infiltration, as well as demonstrate variations in their relationship across different regions of the CNS.
Discriminating Sleep From Freezing With Cortical Spindle Oscillations
Authors: Pompili Marco N. , Todorova Ralitsa
Published: March 2022

In-vivo longitudinal recordings require reliable means to automatically discriminate between distinct behavioral states, in particular between awake and sleep epochs. The typical approach is to use some measure of motor activity together with extracellular electrophysiological signals, namely the relative contribution of theta and delta frequency bands to the Local Field Potential (LFP). However, these bands can partially overlap with oscillations characterizing other behaviors such as the 4 Hz accompanying rodent freezing. Here, we first demonstrate how standard methods fail to discriminate between sleep and freezing in protocols where both behaviors are observed. Then, as an alternative, we propose to use the smoothed cortical spindle power to detect sleep epochs. Finally, we show the effectiveness of this method in discriminating between sleep and freezing in our recordings.
Maximal Dependence Capturing as a Principle of Sensory Processing
Authors: Raj Rishabh , Dahlen Dar , Duyck Kyle , Yu C. Ron
Published: March 2022

Sensory inputs conveying information about the environment are often noisy and incomplete, yet the brain can achieve remarkable consistency in recognizing objects. Presumably, transforming the varying input patterns into invariant object representations is pivotal for this cognitive robustness. In the classic hierarchical representation framework, early stages of sensory processing utilize independent components of environmental stimuli to ensure efficient information transmission. Representations in subsequent stages are based on increasingly complex receptive fields along a hierarchical network. This framework accurately captures the input structures; however, it is challenging to achieve invariance in representing different appearances of objects. Here we assess theoretical and experimental inconsistencies of the current framework. In its place, we propose that individual neurons encode objects by following the principle of maximal dependence capturing (MDC), which compels each neuron to capture the structural components that contain maximal information about specific objects. We implement the proposition in a computational framework incorporating dimension expansion and sparse coding, which achieves consistent representations of object identities under occlusion, corruption, or high noise conditions. The framework neither requires learning the corrupted forms nor comprises deep network layers. Moreover, it explains various receptive field properties of neurons. Thus, MDC provides a unifying principle for sensory processing.
Investigating the Anatomy and Microstructure of the Dentato-rubro-thalamic and Subthalamo-ponto-cerebellar Tracts in Parkinson's Disease
Authors: Lipp Ilona , Mole Jilu Princy , Subramanian Leena , Linden David E. J. , Metzler-Baddeley Claudia
Published: March 2022

Cerebellar-thalamic connections play a central role in deep brain stimulation-based treatment of tremor syndromes. Here, we used diffusion Magnetic Resonance Imaging (MRI) tractography to delineate the main cerebellar peduncles as well as two main white matter tracts that connect the cerebellum with the thalamus, the dentato-rubro-thalamic tract (DRTT) and the subthalamo-ponto-cerebellar tract (SPCT). We first developed a reconstruction protocol in young healthy adults with high-resolution diffusion imaging data and then demonstrate feasibility of transferring this protocol to clinical studies using standard diffusion MRI data from a cohort of patients with Parkinson's disease (PD) and their matched healthy controls. The tracts obtained closely corresponded to the previously described anatomical pathways and features of the DRTT and the SPCT. Second, we investigated the microstructure of these tracts with fractional anisotropy (FA), radial diffusivity (RD), and hindrance modulated orientational anisotropy (HMOA) in patients with PD and healthy controls. By reducing dimensionality of both the microstructural metrics and the investigated cerebellar and cerebellar-thalamic tracts using principal component analyses, we found global differences between patients with PD and controls, suggestive of higher fractional anisotropy, lower radial diffusivity, and higher hindrance modulated orientational anisotropy in patients. However, separate analyses for each of the tracts did not yield any significant differences. Our findings contribute to the characterization of the distinct anatomical connections between the cerebellum and the diencephalon. Microstructural differences between patients and controls in the cerebellar pathways suggest involvement of these structures in PD, complementing previous functional and diffusion imaging studies.
KCNQ2-Related Neonatal Epilepsy Treated With Vitamin B6: A Report of Two Cases and Literature Review
Authors: Amore Greta , Butera Ambra , Spoto Giulia , Valentini Giulia , Saia Maria Concetta , Salpietro Vincenzo , Calì Francesco , Di Rosa Gabriella , Nicotera Antonio Gennaro
Published: March 2022

Potassium Voltage-Gated Channel Subfamily Q Member 2 (KCNQ2) gene has been initially associated with “Benign familial neonatal epilepsy” (BFNE). Amounting evidence arising by next-generation sequencing techniques have led to the definition of new phenotypes, such as neonatal epileptic encephalopathy (NEE), expanding the spectrum of KCNQ2-related epilepsies. Pyridoxine (PN) dependent epilepsies (PDE) are a heterogeneous group of autosomal recessive disorders associated with neonatal-onset seizures responsive to treatment with vitamin B6 (VitB6). Few cases of neonatal seizures due to KCNQ2 pathogenic variants have been reported as successfully responding to VitB6. We reported two cases of KCNQ2-related neonatal epilepsies involving a 5-year-old male with a paternally inherited heterozygous mutation (c.1639C>T; p.Arg547Trp), and a 10-year-old female with a de novo heterozygous mutation (c.740C>T; p.Ser247Leu). Both children benefited from VitB6 treatment. Although the mechanisms explaining the efficacy of VitB6 in such patients remain unclear, this treatment option in neonatal-onset seizures is easily taken into account in Neonatal Intensive Care Units (NICUs). Further studies should be conducted to better define clinical guidelines and treatment protocols.
Application of the Neuroform Atlas Stent in Intracranial Aneurysms: Current Status
Authors: Hou Kun , Yu Jinlu
Published: March 2022

The Neuroform Atlas stent (NAS) is the successor of the Neuroform EZ stent. The NAS is compatible with a low-profile 0.0165-inch microcatheter and is soft enough to pass through small and highly tortuous vessels. The NAS can be used in treating intracranial aneurysms at almost all locations, and its use is becoming increasingly common. However, there has not yet been a complete review of NAS applications. Therefore, we performed this review, which addresses several aspects of the NAS, mainly including its characteristics, clinical trials of its application in treating aneurysms, deployment techniques for the device, the prognosis and complications of its application in treating aneurysms, and antiplatelet requirements associated with its use. Based on the evidence reviewed here, as well as our experience, we found that the NAS is a promising device for treating intracranial aneurysms, especially complex and distal aneurysms. This stent can also be used as a powerful tool to assist in rescuing coil migration, completing dual-stent reconstruction, and coiling aneurysms via a transcirculation approach. The device may require antiplatelet therapy at a lower dose and over a shorter period than other stents. The deployment of the NAS to assist in aneurysm coiling can yield good clinical outcomes and an acceptable rate of complications. Thus, the NAS is a promising device.
Anodal Transcranial Direct Current Stimulation Could Modulate Cortical Excitability and the Central Cholinergic System in Akinetic Rigid-Type Parkinson's Disease: Pilot Study
Authors: Oh Eungseok , Park Jinse , Youn Jinyoung , Jang Wooyoung
Published: March 2022

Background

Transcranial direct current stimulation (tDCS) is a non-invasive technique that has been widely studied as an alternative treatment for Parkinson's disease (PD). However, its clinical benefit remains unclear. In this study, we aimed to investigate the effect of tDCS on the central cholinergic system and cortical excitability in mainly akinetic rigid-type patients with PD.

Methods

In total, 18 patients with PD were prospectively enrolled and underwent 5 sessions of anodal tDCS on the M1 area, which is on the contralateral side of the dominant hand. We excluded patients with PD who had evident resting tremor of the hand to reduce the artifact of electrophysiologic findings. We compared clinical scales reflecting motor, cognitive, and mood symptoms between pre- and post-tDCS. Additionally, we investigated the changes in electrophysiologic parameters, such as short latency afferent inhibition (SAI) (%), which reflects the central cholinergic system.

Results

The United Parkinson's Disease Rating Scale Part 3 (UPDRS-III), the Korean-Montreal Cognitive Assessment (MoCA-K), and Beck Depression Inventory (BDI) scores were significantly improved after anodal tDCS (p < 0.01, p < 0.01, and p < 0.01). Moreover, motor evoked potential amplitude ratio (MEPAR) (%) and integrated SAI showed significant improvement after tDCS (p < 0.01 and p < 0.01). The mean values of the change in integrated SAI (%) were significantly correlated with the changes in UPDRS-III scores; however, the MoCA-K and BDI scores did not show differences.

Conclusions

Anodal tDCS could influence the central cholinergic system, such as frontal cortical excitability and depression in PD. This mechanism could underlie the clinical benefit of tDCS in patients with PD.
Microvascular Decompression for Trigeminal Neuralgia Caused by Venous Offending on the Ventral Side of the Root Entrance/Exit Zone: Classification and Management Strategy
Authors: Wang Wenhua , Yu Feng , Kwok Sze Chai , Wang Yuhai , Yin Jia
Published: March 2022

Background

Trigeminal neuralgia (TGN) is typically caused by an offending artery (OA) but may also involve an offending vein. Venous offending on the ventral side of the root entrance/exit zone (VO-VREZ) is particularly challenging.

Objective

To analyze the rate and pattern of VO-VREZ and propose management strategy accordingly.

Methods

VO-VREZ was classified into 3 types based on its anatomical relationship with a nerve root (A, the vein was covered by the nerve root entirely; B, the vein was lateral to the nerve root; and C, the vein penetrated the nerve root) and 3 groups based on the absence/presence of offending artery (I, no OA; II, suspected OA; and III, definitive OA).

Results

The analysis included 143 cases with complete follow-up. Type A, B, and C accounted for 11.9, 31.5, and 56.6% of the cases, respectively. Group I, II, and III accounted for 24.5, 26.6, and 49.0%, respectively. Most group I VO-VREZ cases (26 out of 31) were managed with coagulation followed by division. Most group II VO-VREZ cases (31 out of 38) were decompressed with shredded Teflon interposition. Group III VO-VREZ was left in place in all 70 cases. Immediate pain relief was achieved in all cases. Temporary hemifacial hypesthesia occurred in 21 patients (14.7%), among which 14 were managed with Teflon decompression. Within the 4.5-year median follow-up, pain recurred in 11 patients (7.7%), but all with lesser intensity.

Conclusion

VO-VREZ is not uncommon in patients with TGN. Different management strategy should be chosen according to the anatomical feature and the absence/presence of arterial conflict.
Volumetric Brain Loss Correlates With a Relapsing MOGAD Disease Course
Authors: Rechtman Ariel , Brill Livnat , Zveik Omri , Uliel Benjamin , Haham Nitzan , Bick Atira S. , Levin Netta , Vaknin-Dembinsky Adi
Published: March 2022

Background

Myelin oligodendrocyte glycoprotein antibody disorders (MOGAD) have evolved as a distinct group of inflammatory, demyelinating diseases of the CNS. MOGAD can present with a monophasic or relapsing disease course with distinct clinical manifestations.However, data on the disease course and disability outcomes of these patients are scarce. We aim to compare brain volumetric changes for MOGAD patients with different disease phenotypes and HCs.

Methods

Brain magnetic resonance imaging (MRI) scans and clinical data were obtained for 22 MOGAD patients and 22 HCs. Volumetric brain information was determined using volBrain and MDbrain platforms.

Results

We found decreased brain volume in MOGAD patients compared to HCs, as identified in volume of total brain, gray matter, white matter and deep gray matter (DGM) structures. In addition, we found significantly different volumetric changes between patients with relapsing and monophasic disease course, with significantly decreased volume of total brain and DGM, cerebellum and hippocampus in relapsing patients during the first year of diagnosis. A significant negative correlation was found between EDSS and volume of thalamus.

Conclusions

Brain MRI analyses revealed volumetric differences between MOGAD patients and HCs, and between patients with different disease phenotypes. Decreased gray matter volume during the first year of diagnosis, especially in the cerebrum and hippocampus of MOGAD patients was associated with relapsing disease course.
Executive Functions and Impulsivity as Transdiagnostic Correlates of Psychopathology in Childhood: A Behavioral Genetic Analysis
Authors: Freis Samantha M. , Morrison Claire L. , Smolker Harry R. , Banich Marie T. , Kaiser Roselinde H. , Hewitt John K. , Friedman Naomi P.
Published: March 2022

Executive functions (EFs) and impulsivity are dimensions of self-regulation that are both related to psychopathology. However, self-report measures of impulsivity and laboratory EF tasks typically display small correlations, and existing research indicates that impulsivity and EFs may tap separate aspects of self-regulation that independently statistically predict psychopathology in adulthood. However, relationships between EFs, impulsivity, and psychopathology may be different in childhood compared to adulthood. Here, we examine whether these patterns hold in the baseline assessment of the Adolescent Brain and Cognitive Development (ABCD) sample, a national sample of over 11,000 children (including 749 twin pairs) ages 9–10 years. We examine the phenotypic and genetic relationships among latent variables for different components of EFs and multiple facets of impulsivity. Additionally, we assess how EFs and impulsivity relate to composite measures and latent variables of psychopathology derived from parent report. EFs were weakly correlated with impulsivity, and the strength varied by impulsivity facet, emphasizing their separability. We did not identify significant genetic and environmental correlations between EFs and impulsivity. Moreover, controlling for their small relationships with each other, both EFs and some facets of impulsivity statistically predicted an Externalizing factor, attention problems, and social problems, and twin analyses suggested these relationships were genetic in origin. These findings indicate that EFs and impulsivity represent phenotypically and genetically separable aspects of self-regulation that are both transdiagnostic correlates of psychopathology in childhood.
Sleep Habits, Quality of Life and Psychosocial Aspects in the Older Age: Before and During COVID-19
Authors: Almondes Katie Moraes de , Castro Eleni de Araujo Sales , Paiva Teresa
Published: March 2022

Aim

This study aimed to describe sleep habits, quality of life and psychosocial aspects in older people and analyze associated differences considering the time before COVID-19 pandemic and during its first wave in Portugal.

Methods

Online survey used for data collection received answers from 914 elderly (age range 65 – 90y), from April to August 2020.

Results

Symptoms of self-perception of depression, anxiety, irritability and economic problems were not prominent in the elderly, except for worries concerning uncertainty about the future. There was no difference in sleep duration before and during the pandemic, although there was a worsening of some aspects related to sleep, such as sleep quality, sleep efficiency, awakening quality, sleep latency and nocturnal awakenings. Gender comparisons showed a higher vulnerability in women. Some morbidities got worse during the pandemic among the elderly, such as Insomnia, Headaches, Depression, Tinnitus, among others.

Conclusion

Even though our data suggest that the pandemic did not have a great impact on quality of life, sleep quality and psychosocial aspects in the elderly, they were still affected by the worsening of their health conditions, including sleep and morbidities. Some behaviors may act as protective factors in this population, such as walking and keeping contact with others, as well as other aspects like financial stability, high level of education and family support, as they can help them to cope better with difficulties.
Genetic Inhibition of Plppr5 Aggravates Hypoxic-Ischemie-Induced Cortical Damage and Excitotoxic Phenotype
Authors: Sun Yuxiao , Jin Mei-fang , Li Lili , Liu Yueying , Wang Dandan , Ni Hong
Published: March 2022

Hypoxia-ischemia (HI) is the most common acute brain threat in neonates and a leading cause of neurodevelopmental impairment. Exploring the new molecular mechanism of HI brain injury has important clinical translational significance for the next clinical intervention research. Lipid phosphatase-related proteins (PLPPRs) are regulators of mitochondrial membrane integrity and energy metabolism. We recently found that Plppr5 knockout exacerbated HI impairment in some aspects and partially attenuated the neuroprotective effects of melatonin, suggesting that Plppr5 may be a novel intervention target for HI. The present study aimed to determine the long-term effects of gene knockout of Plppr5 on HI brain injury, focusing on the neuronal excitability phenotype, and to determine the effect of Plppr5 gene silencing on neuronal zinc metabolism and mitochondrial function in vitro. 10-day-old wild type (WT) mice and Plppr5-deficient (Plppr5–/–) mice were subjected to hypoxia-ischemia. Lesion volumes and HI-induced neuroexcitotoxic phenotypes were quantified together with ZnT1 protein expression in hippocampus. In addition, HT22 (mouse hippocampal neuronal cells) cell model was established by oxygen–glucose deprivation/reoxygenation (OGD/R) treatment and was treated with medium containing LV-sh_Plppr5 or control virus. Mitochondrial oxidative stress indicator ROS, mitochondrial ZnT1 protein expression and zinc ion content were detected.

Results

Plppr5-deficient mice subjected to hypoxia-ischemia at postnatal day 10 present significantly higher cerebral infarction. Plppr5-deficient mice were endowed with a more pronounced superexcitability phenotype at 4 weeks after HI, manifested as a reduced seizure threshold. ZnT1 protein was also found reduced in Plppr5-deficient mice as well as in mice subjected to HI excitotoxicity. Plppr5 knockout in vivo exacerbates HI brain injury phenotypes, including infarct volume and seizure threshold. In addition, knockout of the Plppr5 gene reduced the MFS score to some extent. In vitro Plppr5 silencing directly interferes with neuronal zinc metabolism homeostasis and exacerbates hypoxia-induced mitochondrial oxidative stress damage. Taken together, our findings demonstrate for the first time that Plppr5-deficient mouse pups exposed to neuronal hypoxia and ischemia exhibit aggravated acute brain injury and long-term brain excitability compared with the same treated WT pups, which may be related to the disruption of zinc and mitochondria-dependent metabolic pathways in the hippocampus. These data support further investigation into novel approaches targeting Plppr5-mediated zinc and mitochondrial homeostasis in neonatal HIE.
Imaging Synaptic Density: The Next Holy Grail of Neuroscience?
Authors: Serrano Maria Elisa , Kim Eugene , Petrinovic Marija M. , Turkheimer Federico , Cash Diana
Published: March 2022

The brain is the central and most complex organ in the nervous system, comprising billions of neurons that constantly communicate through trillions of connections called synapses. Despite being formed mainly during prenatal and early postnatal development, synapses are continually refined and eliminated throughout life via complicated and hitherto incompletely understood mechanisms. Failure to correctly regulate the numbers and distribution of synapses has been associated with many neurological and psychiatric disorders, including autism, epilepsy, Alzheimer’s disease, and schizophrenia. Therefore, measurements of brain synaptic density, as well as early detection of synaptic dysfunction, are essential for understanding normal and abnormal brain development. To date, multiple synaptic density markers have been proposed and investigated in experimental models of brain disorders. The majority of the gold standard methodologies (e.g., electron microscopy or immunohistochemistry) visualize synapses or measure changes in pre- and postsynaptic proteins ex vivo. However, the invasive nature of these classic methodologies precludes their use in living organisms. The recent development of positron emission tomography (PET) tracers [such as (18F)UCB-H or (11C)UCB-J] that bind to a putative synaptic density marker, the synaptic vesicle 2A (SV2A) protein, is heralding a likely paradigm shift in detecting synaptic alterations in patients. Despite their limited specificity, novel, non-invasive magnetic resonance (MR)-based methods also show promise in inferring synaptic information by linking to glutamate neurotransmission. Although promising, all these methods entail various advantages and limitations that must be addressed before becoming part of routine clinical practice. In this review, we summarize and discuss current ex vivo and in vivo methods of quantifying synaptic density, including an evaluation of their reliability and experimental utility. We conclude with a critical assessment of challenges that need to be overcome before successfully employing synaptic density biomarkers as diagnostic and/or prognostic tools in the study of neurological and neuropsychiatric disorders.
Evaluation of Real-Time Endogenous Brain-Computer Interface Developed Using Ear-Electroencephalography
Authors: Choi Soo-In , Lee Ji-Yoon , Lim Ki Moo , Hwang Han-Jeong
Published: March 2022

While previous studies have demonstrated the feasibility of using ear-electroencephalography (ear-EEG) for the development of brain-computer interfaces (BCIs), most of them have been performed using exogenous paradigms in offline environments. To verify the reliable feasibility of constructing ear-EEG-based BCIs, the feasibility of using ear-EEG should be further demonstrated using another BCI paradigm, namely the endogenous paradigm, in real-time online environments. Exogenous and endogenous BCIs are to use the EEG evoked by external stimuli and induced by self-modulation, respectively. In this study, we investigated whether an endogenous ear-EEG-based BCI with reasonable performance can be implemented in online environments that mimic real-world scenarios. To this end, we used three different mental tasks, i.e., mental arithmetic, word association, and mental singing, and performed BCI experiments with fourteen subjects on three different days to investigate not only the reliability of a real-time endogenous ear-EEG-based BCI, but also its test-retest reliability. The mean online classification accuracy was almost 70%, which was equivalent to a marginal accuracy for a practical two-class BCI (70%), demonstrating the feasibility of using ear-EEG for the development of real-time endogenous BCIs, but further studies should follow to improve its performance enough to be used for practical ear-EEG-based BCI applications.
Enhanced Resting-State Functional Connectivity of the Nucleus Accumbens in First-Episode, Medication-Naïve Patients With Early Onset Schizophrenia
Authors: Cao Xiaohua , Li Qiang , Liu Sha , Li Zexuan , Wang Yanfang , Cheng Long , Yang Chengxiang , Xu Yong
Published: March 2022

There is abundant evidence that early onset schizophrenia (EOS) is associated with abnormalities in widespread regions, including the cortical, striatal, and limbic areas. As a main component of the ventral striatum, the nucleus accumbens (NAc) is implicated in the pathology of schizophrenia. However, functional connection patterns of NAc in patients with schizophrenia, especially EOS, are seldom explored. A total of 78 first-episode, medication-naïve patients with EOS and 90 healthy controls were recruited in the present study, and resting-state, seed-based functional connectivity (FC) analyses were performed to investigate temporal correlations between NAc and the rest of the brain in the two groups. Additionally, correlation analyses were done between regions showing group differences in NAc functional integration and clinical features of EOS. Group comparison found enhanced FC of the NAc in the EOS group relative to the HCs with increased FC in the right superior temporal gyrus and left superior parietal gyrus with the left NAc region of interest (ROI) and elevated FC in left middle occipital gyrus with the right NAc ROI. No significant associations were found between FC strength and symptom severity as well as the age of the patients. Our findings reveal abnormally enhanced FC of the NAc with regions located in the temporal, parietal, and occipital areas, which were implicated in auditory/visual processing, sensorimotor integration, and cognitive functions. The results suggest disturbed relationships between regions subserving reward, salience processing, and regions subserving sensory processing as well as cognitive functions, which may deepen our understanding of the role of NAc in the pathology of EOS.
Comparison of the Index of Nutritional Quality in Breast Cancer Patients With Healthy Women
Authors: Behrad Nasab Mojgan , Afsharfar Maryam , Ahmadzadeh Mina , Vahid Farhad , Gholamalizadeh Maryam , Abbastorki Saheb , Davoodi Sayed Hossein , Majidi Nazanin , Akbari Mohammad Esmail , Doaei Saeid
Published: March 2022

Background

The index of nutritional quality (INQ) is derived from the food frequency questionnaire (FFQ) and is a method of quantitative and qualitative analysis of diet. This study aimed to compare the INQ for different dietary components between breast cancer (BC) patients and healthy control.

Methods

This case-control study was performed on 180 women with BC and 360 healthy women. Data on general characteristics, medical history, anthropometric indices, physical activity, alcohol consumption, reproductive history, smoking, and dietary intake were collected. A valid FFQ was used to assess the intake of nutrients and the INQ was calculated based on the daily intake of the nutrients.

Results

There was a significant association between BC and INQ of vitamin A (OR = 0.07, 0.01–0.29), vitamin E (OR = 0.43, 0.20–0.93), vitamin B6 (OR = 0.003, 0.000–0.021), riboflavin (OR = 0.25, 0.11–0.59), vitamin K (OR = 0.58, 0.37–0.90), biotin (OR = 0.07, 0.02–0.26), vitamin B12 (OR = 0.32, 0.18–0.56), vitamin C (OR = 0.72, 0.55–0.95), zinc (OR = 0.020, 0.005–0.083), calcium (OR = 0.14, 0.04–0.54) and magnesium (OR = 0.003, 0.000–0.024). Further adjustment for BMI disappeared the association between INQ of vitamin C and BC. The results did not change after further adjustments for waist circumstance and total calorie intake

Conclusion

A significant association was observed between BC and the INQ of vitamin A, vitamin E, vitamin B6, riboflavin, vitamin K, biotin, vitamin B12, vitamin C, zinc, calcium, and magnesium. The INQ can be used as an indicator in assessing clinical nutrition-related problems. Future longitudinal studies are needed to confirm these results.
An Overlooked Prebiotic: Beneficial Effect of Dietary Nucleotide Supplementation on Gut Microbiota and Metabolites in Senescence-Accelerated Mouse Prone-8 Mice
Authors: Ding Ting , Xu Meihong , Li Yong
Published: March 2022

Nucleotides (NTs) are regulatory factors in many biological processes and play important roles in the growth, development, and metabolism of living organisms. We used senescence-accelerated mouse prone-8 (SAMP8) to investigate the effects of NTs on the gut microbiota and metabolites. And the promoting effect of NTs on the growth of a probiotic (Lactobacillus casei) was explored through in vitro experiments. The results showed that the sequencing depth of 16S rDNA covered all microbial species in the feces of SAMP8. Supplementation with exogenous NTs to the diet enhanced the diversity of the gut microbiota, reduced the abundance of bacteria with negative effects on the body (such as Verrucomicrobia, Ruminococcaceae, Akkermansia and Helicobacter), and increased the abundance of the microbiota, which had beneficial effects on the mice (such as Lactobacillus, Candidatus saccharimonas and Lachnospiraceae_NK4A136_group). Metabonomic analysis showed that NT deficiency in the diet significantly affected metabolites in the mouse feces. The metabolites in mice supplemented with NTs tended to be normal (SAMR1). The differentially expressed metabolites caused by NT addition are involved in various pathways in the body, including linoleic acid metabolism, vitamin B6 metabolism, and histidine metabolism. Correlation analysis revealed a significant correlation between the gut microbiota and differentially expressed metabolites caused by the addition of NTs. In vitro experiments showed that NTs significantly promoted the growth, secretion of biofilm and extracellular polymeric substance of L. casei. NTs also promoted the ability of the crude extract of L. casei to resist the secretion of Shigella biofilm. Thus, NTs can regulate the abundance of the gut microbiota and alter the metabolic expression of the intestinal microbiome.
Effect of Green Tea Extract and Soy Isoflavones on the Pharmacokinetics of Rosuvastatin in Healthy Volunteers
Authors: Zeng Weiwei , Hu Miao , Lee Hon Kit , Wat Elaine , Lau Clara Bik San , Ho Chung Shun , Wong Chun Kwok , Tomlinson Brian
Published: March 2022

Background and Aim

Green tea and soy products are extensively consumed in daily life. Research has shown that green tea catechins and soy isoflavones may influence the activity of drug metabolizing enzymes and drug transporters. We examined whether regular consumption of green tea extract or soy isoflavones affected the pharmacokinetics of a single dose of rosuvastatin in healthy subjects and whether any interactions were influenced by the polymorphism in the drug transporter ABCG2.

Study Design

This was an open-label, three-phase randomized crossover study with single doses of rosuvastatin.

Methods

Healthy Chinese male subjects were given a single dose of rosuvastatin 10 mg on 3 occasions: 1. without herbs; 2. with green tea extract; 3. with soy isoflavone extract. The green tea and soy isoflavone extract were given at a dose containing EGCG 800 mg once daily or soy isoflavones−80 mg once daily for 14 days before statin dosing and at the same time as the statin dosing with at least 4-weeks washout period between phases.

Results

Twenty healthy male subjects completed the study and the intake of green tea extract significantly reduced the systemic exposure to rosuvastatin by about 20% reducing AUC0−24h from [geometric mean (% coefficient of variation)] 108.7 (28.9) h·μg/L to 74.1 (35.3) h·μg/L and Cmax from 13.1 (32.2) μg/L to 7.9 (38.3) μg/L (P < 0.001 for both), without affecting the elimination half-life. The ABCG2 421C>A polymorphism had a significant effect on rosuvastatin exposure but no impact on the interaction with green tea. Soy isoflavones had no significant effect on rosuvastatin pharmacokinetics.

Conclusion

This study showed that repeated administration of green tea extract significantly reduced the systemic exposure of rosuvastatin in healthy volunteers. These effects might be predicted to either reduce or increase the lipid-lowering effect of rosuvastatin depending on the mechanism of the effect.
The 2018 Revision of Italian Dietary Guidelines: Development Process, Novelties, Main Recommendations, and Policy Implications
Authors: Rossi Laura , Berni Canani Sibilla , Censi Laura , Gennaro Laura , Leclercq Catherine , Scognamiglio Umberto , Sette Stefania , Ghiselli Andrea
Published: March 2022

The fourth edition of the Italian Dietary Guidelines (IDGs) for Healthy Eating was published in 2019. The objective of this paper is to describe the developmental process of IDGs, the main recommendations, the differences with previous revisions, and the concordance and differences with international guidance on a healthy diet. A National Commission oversaw IDG development. A Scientific Dossier (SD), including analysis on nutrition, health, and risk factors status in Italy, was the reference for IDGs preparation. The IDGs are based on the principles of the Mediterranean Diet and are mainly aimed to prevent obesity and nutrition-related non-communicable diseases. The IDGs included 13 directives that were divided into four conceptual blocks: i) how to balance weight; ii) foods to be promoted; iii) foods to be limited; and iv) how to ensure a varied and sustainable diet. Each directive has a box summarizing the key recommendation, myths lists, and false beliefs to be dispelled. The topics of sustainability and the correct approach to food supplementation and weight-loss diet were introduced in the present edition of IDGs. This paper contributes to the debate on the complexity of derivation of Dietary Guidelines and their adaptation to the national context.
Autophagy-Related Signatures as Prognostic Indicators for Hepatocellular Carcinoma
Authors: Ye Wen , Shi Zhehao , Zhou Yilin , Zhang Zhongjing , Zhou Yi , Chen Bicheng , Zhang Qiyu
Published: March 2022

Background

Hepatocellular carcinoma (HCC) is the most common and deadly type of liver cancer. Autophagy is the process of transporting damaged or aging cellular components into lysosomes for digestion and degradation. Accumulating evidence implies that autophagy is a key factor in tumor progression. The aim of this study was to determine a panel of novel autophagy-related prognostic markers for liver cancer.

Methods

We conducted a comprehensive analysis of autophagy-related gene (ARG) expression profiles and corresponding clinical information based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The univariate Cox proportional regression model was used to screen candidate autophagy-related prognostic genes. In addition, a multivariate Cox proportional regression model was used to identify five key prognostic autophagy-related genes (ATIC, BAX, BIRC5, CAPNS1, and FKBP1A), which were used to construct a prognostic signature. Real-time qPCR analysis was used to evaluate the expression levels of ARGs in 20 surgically resected HCC samples and matched tumor-adjacent normal tissue samples. In addition, the effect of FKBP1A on autophagy and tumor progression was determined by performing in vitro and in vivo experiments.

Results

Based on the prognostic signature, patients with liver cancer were significantly divided into high-risk and low-risk groups in terms of overall survival (OS). A subsequent multivariate Cox regression analysis indicated that the prognostic signature remained an independent prognostic factor for OS. The prognostic signature possessing a better area under the curve (AUC) displayed better performance in predicting the survival of patients with HCC than other clinical parameters. Furthermore, FKBP1A was overexpressed in HCC tissues, and knockdown of FKBP1A impaired cell proliferation, migration, and invasion through the PI3K/AKT/mTOR signaling pathway.

Conclusion

This study provides a prospective biomarker for monitoring outcomes of patients with HCC.