bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Cbk-Like Phage Infecting Erythrobacter, Representing a Novel Siphoviral Genus
Authors: Li Xuejing , Guo Ruizhe , Zou Xiao , Yao Yanyan , Lu Longfei
Published: May 2022

Erythrobacter is an important and widespread bacterial genus in the ocean. However, our knowledge about their phages is still rare. Here, a novel lytic phage vB_EliS-L02, infecting Erythrobacter litoralis DSM 8509, was isolated and purified from Sanggou Bay seawater, China. Morphological observation revealed that the phage belonged to Cbk-like siphovirus, with a long prolate head and a long tail. The host range test showed that phage vB_EliS-L02 could only infect a few strains of Erythrobacter, demonstrating its potential narrow-host range. The genome size of vB_EliS-L02 was 150,063 bp with a G+C content of 59.43%, encoding 231 putative open reading frames (ORFs), but only 47 were predicted to be functional domains. Fourteen auxiliary metabolic genes were identified, including phoH that may confer vB_EliS-L02 the advantage of regulating phosphate uptake and metabolism under a phosphate-limiting condition. Genomic and phylogenetic analyses indicated that vB_EliS-L02 was most closely related to the genus Lacusarxvirus with low similarity (shared genes < 30%, and average nucleotide sequence identity < 70%), distantly from other reported phages, and could be grouped into a novel viral genus cluster, in this study as Eliscbkvirus. Meanwhile, the genus Eliscbkvirus and Lacusarxvirus stand out from other siphoviral genera and could represent a novel subfamily within Siphoviridae, named Dolichocephalovirinae-II. Being a representative of an understudied viral group with manifold adaptations to the host, phage vB_EliS-L02 could improve our understanding of the virus–host interactions and provide reference information for viral metagenomic analysis in the ocean.
Characterization of a New Multifunctional GH20 β-N-Acetylglucosaminidase From Chitinibacter sp. GC72 and Its Application in Converting Chitin Into N-Acetyl Glucosamine
Authors: Chen Yan , Zhou Ning , Chen Xueman , Wei Guoguang , Zhang Alei , Chen Kequan , Ouyang Pingkai
Published: May 2022

In this study, a gene encoding β-N-acetylglucosaminidase, designated NAGaseA, was cloned from Chitinibacter sp. GC72 and subsequently functional expressed in Escherichia coli BL21 (DE3). NAGaseA contains a glycoside hydrolase family 20 catalytic domain that shows low identity with the corresponding domain of the well-characterized NAGases. The recombinant NAGaseA had a molecular mass of 92 kDa. Biochemical characterization of the purified NAGaseA revealed that the optimal reaction condition was at 40°C and pH 6.5, and exhibited great pH stability in the range of pH 6.5–9.5. The Vmax, Km, kcat, and kcat/Km of NAGaseA toward p-nitrophenyl-N-acetyl glucosaminide (pNP-GlcNAc) were 3333.33 μmol min–1 l–1, 39.99 μmol l–1, 4667.07 s–1, and 116.71 ml μmol–1 s–1, respectively. Analysis of the hydrolysis products of N-acetyl chitin oligosaccharides (N-Acetyl COSs) indicated that NAGaseA was capable of converting N-acetyl COSs ((GlcNAc)2–(GlcNAc)6) into GlcNAc with hydrolysis ability order: (GlcNAc)2 > (GlcNAc)3 > (GlcNAc)4 > (GlcNAc)5 > (GlcNAc)6. Moreover, NAGaseA could generate (GlcNAc)3–(GlcNAc)6 from (GlcNAc)2–(GlcNAc)5, respectively. These results showed that NAGaseA is a multifunctional NAGase with transglycosylation activity. In addition, significantly synergistic action was observed between NAGaseA and other sources of chitinases during hydrolysis of colloid chitin. Finally, 0.759, 0.481, and 0.986 g/l of GlcNAc with a purity of 96% were obtained using three different chitinase combinations, which were 1.61-, 2.36-, and 2.69-fold that of the GlcNAc production using the single chitinase. This observation indicated that NAGaseA could be a potential candidate enzyme in commercial GlcNAc production.
Antitoxin CrlA of CrlTA Toxin–Antitoxin System in a Clinical Isolate Pseudomonas aeruginosa Inhibits Lytic Phage Infection
Authors: Ni Muyang , Lin Jianzhong , Gu Jiayu , Lin Shituan , He Mei , Guo Yunxue
Published: May 2022

Pseudomonas aeruginosa is an important opportunistic pathogen in cystic fibrosis patients and immunocompromised individuals, and the toxin–antitoxin (TA) system is involved in bacterial virulence and phage resistance. However, the roles of TA systems in P. aeruginosa are relatively less studied and no phage Cro-like regulators were identified as TA components. Here, we identified and characterized a chromosome-encoded prophage Cro-like antitoxin (CrlA) in the clinical isolate P. aeruginosa WK172. CrlA neutralized the toxicity of the toxin CrlA (CrlT) which cleaves mRNA, and they formed a type II TA system. Specifically, crlA and crlT are co-transcribed and their protein products interact with each other directly. The autorepression of CrlA is abolished by CrlT through the formation of the CrlTA complex. Furthermore, crlTA is induced in the stationary phase, and crlA is expressed at higher levels than crlT. The excess CrlA inhibits the infection of lytic Pseudomonas phages. CrlA is widely distributed among Pseudomonas and in other bacterial strains and may provide antiphage activities.
Potential of Natural Alkaloids From Jadwar (Delphinium denudatum) as Inhibitors Against Main Protease of COVID-19: A Molecular Modeling Approach
Authors: Kumar Anuj , Sharma Mansi , Richardson Christopher D. , Kelvin David J.
Published: May 2022

The ongoing pandemic coronavirus disease (COVID-19) caused by a novel corona virus, namely, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has had a major impact on global public health. COVID-19 cases continue to increase across the globe with high mortality rates in immunocompromised patients. There is still a pressing demand for drug discovery and vaccine development against this highly contagious disease. To design and develop antiviral drugs against COVID-19, the main protease (Mpro) has emerged as one of the important drug targets. In this context, the present work explored Jadwar (Delphinium denudatum)–derived natural alkaloids as potential inhibitors against Mpro of SARS-CoV-2 by employing a combination of molecular docking and molecular dynamic simulation–based methods. Molecular docking and interaction profile analysis revealed strong binding on the Mpro functional domain with four natural alkaloids viz. panicutine (−7.4 kcal/mol), vilmorrianone (−7.0 kcal/mol), denudatine (−6.0 kcal/mol), and condelphine (−5.9 kcal/mol). The molecular docking results evaluated by using the MD simulations on 200 nanoseconds confirmed highly stable interactions of these compounds with the Mpro. Additionally, mechanics/generalized Born/Poisson–Boltzmann surface area (MM/G/P/BSA) free energy calculations also affirmed the docking results. Natural alkaloids explored in the present study possess the essential drug-likeness properties, namely, absorption, distribution, metabolism, and excretion (ADME), and are in accordance with Lipinski’s rule of five. The results of this study suggest that these four bioactive molecules, namely, condelphine, denudatine, panicutine, and vilmorrianone, might be effective candidates against COVID-19 and can be further investigated using a number of experimental methods.
Understanding the P-Loop Conformation in the Determination of Inhibitor Selectivity Toward the Hepatocellular Carcinoma-Associated Dark Kinase STK17B
Authors: Liu Chang , Li Zhizhen , Liu Zonghan , Yang Shiye , Wang Qing , Chai Zongtao
Published: May 2022

As a member of the death-associated protein kinase family of serine/threonine kinases, the STK17B has been associated with diverse diseases such as hepatocellular carcinoma. However, the conformational dynamics of the phosphate-binding loop (P-loop) in the determination of inhibitor selectivity profile to the STK17B are less understood. Here, a multi-microsecond length molecular dynamics (MD) simulation of STK17B in the three different states (ligand-free, ADP-bound, and ligand-bound states) was carried out to uncover the conformational plasticity of the P-loop. Together with the analyses of principal component analysis, cross-correlation and generalized correlation motions, secondary structural analysis, and community network analysis, the conformational dynamics of the P-loop in the different states were revealed, in which the P-loop flipped into the ADP-binding site upon the inhibitor binding and interacted with the inhibitor and the C-lobe, strengthened the communication between the N- and C-lobes. These resulting interactions contributed to inhibitor selectivity profile to the STK17B. Our results may advance our understanding of kinase inhibitor selectivity and offer possible implications for the design of highly selective inhibitors for other protein kinases.
Identifying Methylation Signatures and Rules for COVID-19 With Machine Learning Methods
Authors: Li Zhandong , Mei Zi , Ding Shijian , Chen Lei , Li Hao , Feng Kaiyan , Huang Tao , Cai Yu-Dong
Published: May 2022

The occurrence of coronavirus disease 2019 (COVID-19) has become a serious challenge to global public health. Definitive and effective treatments for COVID-19 are still lacking, and targeted antiviral drugs are not available. In addition, viruses can regulate host innate immunity and antiviral processes through the epigenome to promote viral self-replication and disease progression. In this study, we first analyzed the methylation dataset of COVID-19 using the Monte Carlo feature selection method to obtain a feature list. This feature list was subjected to the incremental feature selection method combined with a decision tree algorithm to extract key biomarkers, build effective classification models and classification rules that can remarkably distinguish patients with or without COVID-19. EPSTI1, NACAP1, SHROOM3, C19ORF35, and MX1 as the essential features play important roles in the infection and immune response to novel coronavirus. The six significant rules extracted from the optimal classifier quantitatively explained the expression pattern of COVID-19. Therefore, these findings validated that our method can distinguish COVID-19 at the methylation level and provide guidance for the diagnosis and treatment of COVID-19.
A Double-Edged Sword: The Role of Prior Knowledge in Memory Aging
Authors: Chen Xi , Varghese Leah , Jagust William J.
Published: May 2022

Introduction

People accumulate knowledge throughout their lifespan and the accumulated knowledge influences how we encode and retrieve information in memory processing. This study aims to investigate the role of knowledge in associative memory across the adult lifespan, and specifically examines the effects of two material properties that interact with prior knowledge: congruency – whether the material is congruent with people’s prior knowledge, and ambiguity – whether the material is ambiguous to interpret based on prior knowledge.

Method

273 participants (aged 22–70 years old) completed an incidental memory task online. Participants were shown pictures depicting an object in a scene and judged if the object was likely or unlikely to be in the particular scene. Later, in the recognition test, participants were asked to identify if the exact picture was presented earlier. The pictures were manipulated to have varying levels of congruency, meaning that some depicted likely object–scene pairs and some unlikely. We also measured how different the likely/unlikely judgment for each object–scene pair was across all participants to determine the ambiguity level of the object–scene pair: some were more likely to receive diverse responses across people, whereas others are unambiguously consistent (or inconsistent) with common knowledge shared by most people. We used mixed-effects logistic regressions to predict memory outcome for each trial as a function of age, age2, congruency/ambiguity, and their interactions.

Results

The object–scene pairs perceived as congruent had higher hit rates than incongruent ones, as well as higher false alarm rates, especially in middle-aged and older people. Higher ambiguity was also related to both greater true and false memory, independent of age. Finally, the effect of ambiguity only emerged when the object–scene pair was perceived incongruent.

Discussion

The results suggest that people rely on prior knowledge to process new information and that this reliance improves hit responses, but also induces false memories particularly for middle-aged and older people, suggesting a double-edged role of knowledge in associative memory and its disproportionate influence on memory aging. Over-reliance on knowledge in older adults, which has been suspected in other cognitive processes, may be one of the mechanisms underlying associative memory decrease in aging.
Building an Affordances Map With Interactive Perception
Authors: Le Goff Léni K. , Yaakoubi Oussama , Coninx Alexandre , Doncieux Stéphane
Published: May 2022

Robots need to understand their environment to perform their task. If it is possible to pre-program a visual scene analysis process in closed environments, robots operating in an open environment would benefit from the ability to learn it through their interaction with their environment. This ability furthermore opens the way to the acquisition of affordances maps in which the action capabilities of the robot structure its visual scene understanding. We propose an approach to build such affordances maps by relying on an interactive perception approach and an online classification for a real robot equipped with two arms with 7 degrees of freedom. Our system is modular and permits to learn maps from different skills. In the proposed formalization of affordances, actions and effects are related to visual features, not objects, thus our approach does not need a prior definition of the concept of object. We have tested the approach on three action primitives and on a real PR2 robot.
The Role of Sildenafil in Treating Brain Injuries in Adults and Neonates
Authors: Xiong Ying , Wintermark Pia
Published: May 2022

Sildenafil is a recognized treatment for patients suffering from erectile dysfunction and pulmonary hypertension. However, new evidence suggests that it may have a neuroprotective and a neurorestorative role in the central nervous system of both adults and neonates. Phosphodiesterase type 5—the target of sildenafil—is distributed in many cells throughout the body, including neurons and glial cells. This study is a comprehensive review of the demonstrated effects of sildenafil on the brain with respect to its function, extent of injury, neurons, neuroinflammation, myelination, and cerebral vessels.
Associations of the Severity of Obstructive Sleep Apnea With Age-Related Comorbidities: A Population-Based Study
Authors: Silva Mayra dos Santos , Poyares Dalva , Silva Luciana Oliveira , Souza Ksdy M. , Andersen Monica L. , Ohayon Maurice M. , Tufik Sergio , Piovezan Ronaldo D.
Published: May 2022

Aging is accompanied by changes in the quantity and quality of sleep. Obstructive sleep apnea (OSA) is also more prevalent in the older population. Although severe OSA has been linked to a higher risk of cardiovascular disease regardless of adult age, clinical consequences of mild-to-moderate OSA in the older adults are still uncertain.

Objectives

To investigate the relationships between severity and metabolic, cognitive, and functional characteristics in community-dwelling older adults from a representative sample of the city of São Paulo.

Methods

In total, 199 participants of the first follow-up of the São Paulo Epidemiologic Sleep Study (EPISONO, São Paulo, Brazil) >60 years were cross-sectionally assessed through questionnaires, physical evaluations, laboratory tests, and full in-lab polysomnography (PSG). Three groups according to the OSA severity were compared according to sociodemographic characteristics, anthropometric measures, PSG parameters, the frequency of comorbidities, and the use of medications.

Results

Participants' age ranged from 60 to 87 years with a mean of 70.02 ± 7.31, 59.8% female. In the univariate analysis, body mass index (BMI, kg/m2) (p = 0.049) and waist circumference (p = 0.005) were significantly higher in the participants with moderate OSA, but not among those with severe OSA. Participants with severe OSA had a higher arousal index (p = 0.007). Multivariate analysis showed that severe OSA was significantly associated with hypertension (p = 0.005), heart diseases (p = 0.025), and the use of two or more medications (p = 0.035).

Conclusion

In a population-based study, severe, but not mild-to-moderate, OSA in older adults was associated with hypertension and the use of more medications. As age advances, anthropometric indicators of obesity may not increase the risk of severe OSA.
Epidemiologic Profile of Patients With Epilepsy in a Region of Southeast Brazil: Data From a Referral Center
Authors: Buainain Renata Parissi , Oliveira Carlos Tadeu Parisi , Marson Fernando Augusto Lima , Ortega Manoela Marques
Published: May 2022

Introduction

Epilepsy affects about 50 million people worldwide, 80% of whom live in low- and middle-income countries. In Brazil, epidemiological studies are outdated and restricted to specific regions, mostly due to the continental size of country.

Objective

We aimed to present the first evidence-based study on the epidemiological aspects of individuals with epilepsy, mapping the characteristics of this disease in a referral center in a region of Southeast Brazil.

Methods

A retrospective study was carried out from January 2010 to March 2021. Patients were selected according to the International League Against Epilepsy Criteria.

Results

From a total of 618 selected patients, 317 (51.3%) were men and 301 (48.7%) were women with an average age of 34.03 ± 20.66 years. The average age at the first seizure was 15.16 ± 17.61 years. The prevalence ratio was 1.30 cases/1,000 habitants. Childhood febrile seizure was present in 44 patients (7.9%) and family history of epilepsy in 231 (37.4%) patients. The predominant type of seizure was focal in 401 (64.9%) patients. The most frequent etiologies were structural in 254 (41.1%) patients and unknown in 238 (38.5%) patients. Most of the patients' treatments were based on anti-seizure drugs in monotherapy [389 (62.9%)] with 398 (64.4%) drug-responsive patients.

Conclusions

Our epilepsy prevalence rate was lower than other studies in the Southeast Region of Brazil. In addition, the structural epilepsy type was predominant in our study compared with unknown causes, which is more frequent in other Brazilian regions and worldwide studies. The differences may be attributed to our region, which presents a high prevalence of neuroinfection, specially neurocysticercosis, and a referral center for traumatic brain injury. Moreover, the contrasting results reinforce the need for an adequate epidemiological assessment of epilepsy incidence in a region of Southeast Brazil.
A Multidimensional Investigation of Sensory Processing in Autism: Parent- and Self-Report Questionnaires, Psychophysical Thresholds, and Event-Related Potentials in the Auditory and Somatosensory Modalities
Authors: Dwyer Patrick , Takarae Yukari , Zadeh Iman , Rivera Susan M. , Saron Clifford D.
Published: May 2022

Background

Reconciling results obtained using different types of sensory measures is a challenge for autism sensory research. The present study used questionnaire, psychophysical, and neurophysiological measures to characterize autistic sensory processing in different measurement modalities.

Methods

Participants were 46 autistic and 21 typically developing 11- to 14-year-olds. Participants and their caregivers completed questionnaires regarding sensory experiences and behaviors. Auditory and somatosensory event-related potentials (ERPs) were recorded as part of a multisensory ERP task. Auditory detection, tactile static detection, and tactile spatial resolution psychophysical thresholds were measured.

Results

Sensory questionnaires strongly differentiated between autistic and typically developing individuals, while little evidence of group differences was observed in psychophysical thresholds. Crucially, the different types of measures (neurophysiological, psychophysical, questionnaire) appeared to be largely independent of one another. However, we unexpectedly found autistic participants with larger auditory Tb ERP amplitudes had reduced hearing acuity, even though all participants had hearing acuity in the non-clinical range.

Limitations

The autistic and typically developing groups were not matched on cognitive ability, although this limitation does not affect our main analyses regarding convergence of measures within autism.

Conclusion

Overall, based on these results, measures in different sensory modalities appear to capture distinct aspects of sensory processing in autism, with relatively limited convergence between questionnaires and laboratory-based tasks. Generally, this might reflect the reality that laboratory tasks are often carried out in controlled environments without background stimuli to compete for attention, a context which may not closely resemble the busier and more complex environments in which autistic people’s atypical sensory experiences commonly occur. Sensory questionnaires and more naturalistic laboratory tasks may be better suited to explore autistic people’s real-world sensory challenges. Further research is needed to replicate and investigate the drivers of the unexpected association we observed between auditory Tb ERP amplitudes and hearing acuity, which could represent an important confound for ERP researchers to consider in their studies.
Brain Under Fatigue – Can Perceived Fatigability in Multiple Sclerosis Be Seen on the Level of Functional Brain Network Architecture?
Authors: Sobczak Anna Maria , Bohaterewicz Bartosz , Ceglarek Anna , Zyrkowska Aleksandra , Fafrowicz Magdalena , Slowik Agnieszka , Wnuk Marcin , Marona Monika , Nowak Klaudia , Zur-Wyrozumska Kamila , Marek Tadeusz
Published: May 2022

Background

Fatigue is one of the most common symptoms of multiple sclerosis (MS), significantly affecting the functioning of the patients. However, the neural underpinnings of physical and mental fatigue in MS are still vague. The aim of our study was to investigate the functional architecture of resting-state networks associated with fatigue in patients with MS.

Methods

The sum of 107 high-functioning patients underwent a resting-state scanning session and filled out the 9-item Fatigue Severity Scale (FSS). Based on the FSS score, we identified patients with different levels of fatigue using the cluster analysis. The low-fatigue group consisted of n = 53 subjects, while the high-fatigue group n = 48. The neuroimaging data were analyzed in terms of functional connectivity (FC) between various resting-state networks as well as amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuations (fALFF).

Results

Two-sample t-test revealed between-group differences in FC of posterior salience network (SN). No differences occurred in default mode network (DMN) and sensorimotor network (SMN). Moreover, differences in fALFF were shown in the right middle frontal gyrus and right superior frontal gyrus, however, no ALFF differences took place.

Conclusion

Current study revealed significant functional network (FN) architecture between-group differences associated with fatigue. Present results suggest the higher level of fatigue is related to deficits in awareness as well as higher interoceptive awareness and nociception.
Combination of Group Singular Value Decomposition and eLORETA Identifies Human EEG Networks and Responses to Transcranial Photobiomodulation
Authors: Wang Xinlong , Wanniarachchi Hashini , Wu Anqi , Liu Hanli
Published: May 2022

Transcranial Photobiomodulation (tPBM) has demonstrated its ability to alter electrophysiological activity in the human brain. However, it is unclear how tPBM modulates brain electroencephalogram (EEG) networks and is related to human cognition. In this study, we recorded 64-channel EEG from 44 healthy humans before, during, and after 8-min, right-forehead, 1,064-nm tPBM or sham stimulation with an irradiance of 257 mW/cm2. In data processing, a novel methodology by combining group singular value decomposition (gSVD) with the exact low-resolution brain electromagnetic tomography (eLORETA) was implemented and performed on the 64-channel noise-free EEG time series. The gSVD+eLORETA algorithm produced 11 gSVD-derived principal components (PCs) projected in the 2D sensor and 3D source domain/space. These 11 PCs took more than 70% weight of the entire EEG signals and were justified as 11 EEG brain networks. Finally, baseline-normalized power changes of each EEG brain network in each EEG frequency band (delta, theta, alpha, beta and gamma) were quantified during the first 4-min, second 4-min, and post tPBM/sham periods, followed by comparisons of frequency-specific power changes between tPBM and sham conditions. Our results showed that tPBM-induced increases in alpha powers occurred at default mode network, executive control network, frontal parietal network and lateral visual network. Moreover, the ability to decompose EEG signals into individual, independent brain networks facilitated to better visualize significant decreases in gamma power by tPBM. Many similarities were found between the cortical locations of SVD-revealed EEG networks and fMRI-identified resting-state networks. This consistency may shed light on mechanistic associations between tPBM-modulated brain networks and improved cognition outcomes.
Test-Retest Reliability of fMRI During an Emotion Processing Task: Investigating the Impact of Analytical Approaches on ICC Values
Authors: Heilicher Mickela , Crombie Kevin M. , Cisler Josh M.
Published: May 2022

Test-retest reliability of fMRI is often assessed using the intraclass correlation coefficient (ICC), a numerical representation of reliability. Reports of low reliability at the individual level may be attributed to analytical approaches and inherent bias/error in the measures used to calculate ICC. It is unclear whether low reliability at the individual level is related to methodological decisions or if fMRI is inherently unreliable. The purpose of this study was to investigate methodological considerations when calculating ICC to improve understanding of fMRI reliability. fMRI data were collected from adolescent females (N = 23) at pre- and post-cognitive behavioral therapy. Participants completed an emotion processing task during fMRI. We calculated ICC values using contrasts and β coefficients separately from voxelwise and network (ICA) analyses of the task-based fMRI data. For both voxelwise analysis and ICA, ICC values were higher when calculated using β coefficients. This work provides support for the use of β coefficients over contrasts when assessing reliability of fMRI, and the use of contrasts may underlie low reliability estimates reported in the existing literature. Continued research in this area is warranted to establish fMRI as a reliable measure to draw conclusions and utilize fMRI in clinical settings.
Does Neuroinflammation Underlie the Cognitive Changes Observed With Dietary Interventions?
Authors: Robbins Jacqueline P. , Solito Egle
Published: May 2022

Dietary interventions, such as calorie restriction and ketogenic diet, have been extensively studied in ageing research, including in cognitive decline. Epidemiological studies indicate beneficial effects of certain dietary regimes on mental health, including mood disorders and dementia. However, randomised-controlled trials (the gold-standard of evidence-based medicine) on calorie restriction diets and the ketogenic diet have yet to show clinically convincing effects in neuropsychiatric disorders. This review will examine the quality of studies and evidence base for the ketogenic and calorie restriction diets in common neuropsychiatric conditions, collating findings from preclinical experiments, case reports or small clinical studies, and randomised controlled clinical trials. The major cellular mechanisms that mediate the effects of these dietary interventions on brain health include neuroinflammation, neuroprotection, and neuromodulation. We will discuss the studies that have investigated the roles of these pathways and their interactions. Popularity of the ketogenic and calorie restriction diets has grown both in the public domain and in psychiatry research, allowing for informed review of the efficacy, the limitations, and the side effects of these diets in specific patient populations. In this review we will summarise the clinical evidence for these diets in neuropsychiatry and make suggestions to improve clinical translation of future research studies.
Site-Specific Regulation of Stress Responses Along the Rostrocaudal Axis of the Insular Cortex in Rats
Authors: Tomeo Rodrigo A. , Gomes-de-Souza Lucas , Benini Ricardo , Reis-Silva Lilian L. , Crestani Carlos C.
Published: May 2022

The insular cortex (IC) has been described as a part of the central network implicated in the integration and processing of limbic information, being related to the behavioral and physiological responses to stressful events. Besides, a site-specific control of physiological functions has been reported along the rostrocaudal axis of the IC. However, a functional topography of the IC in the regulation of stress responses has never been reported. Therefore, this study aimed to investigate the impact of acute restraint stress in neuronal activation at different sites along the rostrocaudal axis of the IC. Furthermore, we evaluated the involvement of IC rostrocaudal subregions in the cardiovascular responses to acute restraint stress. We observed that an acute session of restraint stress increased the number of Fos-immunoreactive cells in the rostral posterior region of the IC, while fewer activated cells were identified in the anterior and caudal posterior regions. Bilateral injection of the non-selective synaptic inhibitor CoCl2 into the anterior region of the IC did not affect the blood pressure and heart rate increases and the sympathetically mediated cutaneous vasoconstriction to acute restraint stress. However, synaptic ablation of the rostral posterior IC decreased the restraint-evoked arterial pressure increase, whereas tachycardia was reduced in animals in which the caudal posterior IC was inhibited. Taken together, these pieces of evidence indicate a site-specific regulation of cardiovascular stress response along the rostrocaudal axis of the IC.
Efficacy and Mechanism of Moxibustion Treatment on Mild Cognitive Impairment Patients: An fMRI Study Using ALFF
Authors: Lai Ziyan , Zhang Qingping , Liang Lingyan , Wei Yichen , Duan Gaoxiong , Mai Wei , Zhao Lihua , Liu Peng , Deng Demao
Published: May 2022

Background

Mild Cognitive Impairment (MCI), as a high risk of Alzheimer’s disease (AD), represents a state of cognitive function between normal aging and dementia. Moxibustion may effectively delay the progression of AD, while there is a lack of studies on the treatments in MCI. This study aimed to evaluate the effect of moxibustion treatment revealed by the amplitude of low-frequency fluctuation (ALFF) in MCI.

Method

We enrolled 30 MCI patients and 30 matched healthy controls (HCs) in this study. We used ALFF to compare the difference between MCI and HCs at baseline and the regulation of spontaneous neural activity in MCI patients by moxibustion. The Mini-Mental State Examination and Montreal Cognitive Assessment scores were used to evaluate cognitive function.

Results

Compared with HCs, the ALFF values significantly decreased in the right temporal poles: middle temporal gyrus (TPOmid), right inferior temporal gyrus, left middle cingulate gyrus, and increased in the left hippocampus, left middle temporal gyrus, right lingual gyrus, and right middle occipital gyrus in MCI patients. After moxibustion treatment, the ALFF values notably increased in the left precuneus, left thalamus, right temporal poles: middle temporal gyrus, right middle frontal gyrus, right inferior temporal gyrus, right putamen, right hippocampus, and right fusiform gyrus, while decreased in the bilateral lingual gyrus in MCI patients. The Mini-Mental State Examination and Montreal Cognitive Assessment scores increased after moxibustion treatment, and the increase in Mini-Mental State Examination score was positively correlated with the increase of ALFF value in the right TPOmid, the right insula, and the left superior temporal gyrus.

Conclusion

Moxibustion treatment might improve the cognitive function of MCI patients by modulating the brain activities within the default mode network, visual network, and subcortical network with a trend of increased ALFF values and functional asymmetry of the hippocampus. These results indicate that moxibustion holds great potential in the treatment of MCI.
Loss of the Sympathetic Signal Produces Sterile Inflammation of the Prostate
Authors: Hu Hao , Cui Yiwen , Yang Jing , Cao Ying
Published: May 2022

Neural innervations exert essential roles in the prostate. However, spatial distribution and regulatory function of such neural inputs are incompletely characterized. Here, we exploited the advanced whole-tissue immunolabeling and optical clearing technique to assess the 3D anatomy of autonomic innervations in the mouse and human prostate for the first time. We observed that sympathetic and parasympathetic inputs in the mouse prostate remained unaffected during castration-induced tissue regression. However, the pharmacologic destruction of sympathetic innervations in the mouse prostate led to sterile inflammation of the tissue, mimicking the disease condition of chronic non-bacterial prostatitis. Also, the genetic ablation of sympathetic inputs produced a similar inflammatory response. Furthermore, we showed that treatment of the specific β2-adrenergic receptor agonists could effectively mitigate the prostate inflammation caused by such sympathetic loss. Together, these results have elucidated the new immunomodulatory function of the sympathetic signal via the β2-adrenergic receptor in prostate inflammatory disease.
Recessive PKD1 Mutations Are Associated With Febrile Seizures and Epilepsy With Antecedent Febrile Seizures and the Genotype-Phenotype Correlation
Authors: Wang Jing-Yang , Wang Jie , Lu Xin-Guo , Song Wang , Luo Sheng , Zou Dong-Fang , Hua Li-Dong , Peng Qian , Tian Yang , Gao Liang-Di , Liao Wei-Ping , He Na
Published: May 2022

Objective

The PKD1 encodes polycystin-1, a large transmembrane protein that plays important roles in cell proliferation, apoptosis, and cation transport. Previous studies have identified PKD1 mutations in autosomal dominant polycystic kidney disease (ADPKD). However, the expression of PKD1 in the brain is much higher than that in the kidney. This study aimed to explore the association between PKD1 and epilepsy.

Methods

Trios-based whole-exome sequencing was performed in a cohort of 314 patients with febrile seizures or epilepsy with antecedent febrile seizures. The damaging effects of variants was predicted by protein modeling and multiple in silico tools. The genotype-phenotype association of PKD1 mutations was systematically reviewed and analyzed.

Results

Eight pairs of compound heterozygous missense variants in PKD1 were identified in eight unrelated patients. All patients suffered from febrile seizures or epilepsy with antecedent febrile seizures with favorable prognosis. All of the 16 heterozygous variants presented no or low allele frequencies in the gnomAD database, and presented statistically higher frequency in the case-cohort than that in controls. These missense variants were predicted to be damaging and/or affect hydrogen bonding or free energy stability of amino acids. Five patients showed generalized tonic-clonic seizures (GTCS), who all had one of the paired missense mutations located in the PKD repeat domain, suggesting that mutations in the PKD domains were possibly associated with GTCS. Further analysis demonstrated that monoallelic mutations with haploinsufficiency of PKD1 potentially caused kidney disease, compound heterozygotes with superimposed effects of two missense mutations were associated with epilepsy, whereas the homozygotes with complete loss of PKD1 would be embryonically lethal.

Conclusion

PKD1 gene was potentially a novel causative gene of epilepsy. The genotype-phenotype relationship of PKD1 mutations suggested a quantitative correlation between genetic impairment and phenotypic variation, which will facilitate the genetic diagnosis and management in patients with PKD1 mutations.
CRISPR-Cas9 Knock-In of T513M and G41S Mutations in the Murine β–Galactosyl-Ceramidase Gene Re-capitulates Early-Onset and Adult-Onset Forms of Krabbe Disease
Authors: Rebiai Rima , Rue Emily , Zaldua Steve , Nguyen Duc , Scesa Giuseppe , Jastrzebski Martin , Foster Robert , Wang Bin , Jiang Xuntian , Tai Leon , Brady Scott T. , van Breemen Richard , Givogri Maria I. , Sands Mark S. , Bongarzone Ernesto R.
Published: May 2022

Krabbe Disease (KD) is a lysosomal storage disorder characterized by the genetic deficiency of the lysosomal enzyme β-galactosyl-ceramidase (GALC). Deficit or a reduction in the activity of the GALC enzyme has been correlated with the progressive accumulation of the sphingolipid metabolite psychosine, which leads to local disruption in lipid raft architecture, diffuse demyelination, astrogliosis, and globoid cell formation. The twitcher mouse, the most used animal model, has a nonsense mutation, which limits the study of how different mutations impact the processing and activity of GALC enzyme. To partially address this, we generated two new transgenic mouse models carrying point mutations frequently found in infantile and adult forms of KD. Using CRISPR-Cas9 gene editing, point mutations T513M (infantile) and G41S (adult) were introduced in the murine GALC gene and stable founders were generated. We show that GALCT513M/T513M mice are short lived, have the greatest decrease in GALC activity, have sharp increases of psychosine, and rapidly progress into a severe and lethal neurological phenotype. In contrast, GALCG41S/G41S mice have normal lifespan, modest decreases of GALC, and minimal psychosine accumulation, but develop adult mild inflammatory demyelination and slight declines in coordination, motor skills, and memory. These two novel transgenic lines offer the possibility to study the mechanisms by which two distinct GALC mutations affect the trafficking of mutated GALC and modify phenotypic manifestations in early- vs adult-onset KD.
Dietary Resistant Starch From Potato Regulates Bone Mass by Modulating Gut Microbiota and Concomitant Short-Chain Fatty Acids Production in Meat Ducks
Authors: Zhang Huaiyong , Qin Simeng , Zhu Yao , Zhang Xiangli , Du Pengfei , Huang Yanqun , Michiels Joris , Zeng Quifeng , Chen Wen
Published: May 2022

Graphical Abstract

Potential mechanisms how supplementation of resistant starch improved the tibia mass of meat duck. Dietary supplementation of 12% raw potato starch modulated gut microbiota and concomitant short-chain fatty acids production, followed by inhibition of inflammation. Consequently, the bone resorption mediated by inflammatory cytokine was decreased, and eventually contributed to a net increase in bone mass.
High Prevalence of Nutritional Risk Among Pulmonary Patients Living on the Tibetan Plateau
Authors: Quncuo Chilie , Liang Ying , Li Qiuyu , She Xiaoli , Cuo Bian Ma , Qiongda Bianba , ChuTso Meilang , Sun Yongchang
Published: May 2022

Background

Nutritional risk is associated with adverse clinical outcomes and is more prevalent among pulmonology patients than among patients in other departments. High-altitude environments can affect patients with chronic respiratory diseases, but evidence of the prevalence of nutritional risk among hospitalized patients with respiratory diseases in high-altitude areas is limited. This study aimed to investigate the nutritional risk and status of inpatients with different major respiratory diagnoses permanently living on the Tibetan Plateau (≥3,000 m above sea level).

Methods

In this cross-sectional study, we consecutively recruited inpatients admitted to the Department of Respiratory and Critical Care Medicine at the Tibet Autonomous Region People's Hospital of Lhasa between November 2020 and May 2021. We used the Nutrition Risk Screening (NRS) 2002 tool to assess nutritional risk among these patients. An NRS 2002 score ≥3 points indicates nutritional risk; a score ≥5 indicates high nutritional risk. According to NRS-2002 scores, patients were divided into three groups (NRS-2002 0–2, 3–4, and ≥5). The differences in age, sex, major respiratory diagnoses, comorbidities, body mass index, and laboratory findings among the groups were analyzed.

Results

A total of 289 eligible Tibetan patients were enrolled in the study, and 46.1% (133/246) of them were at nutritional risk (NRS-2002 score ≥3). Twenty-one (7.3%) patients were at high nutritional risk (NRS-2002 score ≥5). The proportions of patients at nutritional risk were relatively high among patients with lung cancer (58.8%), interstitial lung disease (58.3%), pulmonary embolism (52.9%), and tuberculosis (50.0%). Laboratory findings showed that patients with NRS-2002 scores of 3–4 and ≥5 had lower red blood cell counts, serum albumin and hemoglobin levels, and higher C-reactive protein (CRP) levels than those with NRS-2002 scores < 3.

Conclusion

The prevalence of nutritional risk was high among pulmonology department inpatients permanently living on the Tibetan Plateau. Patients with lung cancer, interstitial lung disease, pulmonary embolism or tuberculosis were more likely to have nutritional risk than patients with other diagnoses. The nutritional risk of inpatients in the respiratory department in the plateau area should not be ignored, and patients at high nutritional risk should receive timely intervention.
Association of Daily Eating Duration and Day-To-Day Variability in the Timing of Eating With Fatal Cancer Risk in Older Men
Authors: Meth Elisa M. S. , van Egmond Lieve T. , Moulin Thiago C. , Cedernaes Jonathan , Rosqvist Fredrik , Benedict Christian
Published: May 2022

Meal timing has significant effects on health. However, whether meal timing is associated with the risk of developing and dying of cancer is not well-researched in humans. In the present study, we used data from 941 community-dwelling men aged 71 years who participated in the Uppsala Longitudinal Study of Adult Men to examine the association of meal timing with cancer morbidity and fatal cancer. The following meal timing variables were derived from 7-day food diaries: (i) daily eating duration, i.e., the time between the first and last eating episode of an arbitrary day; (ii) the calorically weighted midpoint of the daily eating interval, a proxy of when the eating window typically occurs during an arbitrary day; and (iii) the day-to-day variability in the timing of eating. We also assessed the reported daily energy intake reliability using the Goldberg method. During a mean observational period of 13.4 years, 277 men (29.4%) were diagnosed with cancer. Furthermore, 191 men (20%) died from cancer during 14.7 years of follow-up. As shown by Cox regression adjusted for potential confounders (e.g., smoking status and daily energy intake), men with reliable dietary reports whose daily eating intervals were on average 13 h long had a 2.3-fold greater fatal cancer risk than men whose daily eating windows were on average about 11 h long. We also found that men with an average day-to-day variability in the timing of eating of 48 to 74 min had a 2- to 2.2-fold higher fatal cancer risk than those with the lowest average day-to-day variability in the timing of eating (i.e., 23 min). No clear associations were found in men with inadequate dietary reports, emphasizing the need to consider the reliability of dietary records in nutritional epidemiology. To fully unlock its potential, studies are needed to test whether recommendations to time-restrict the 24-h eating interval and reduce day-to-day variability in the timing of eating can meaningfully alter the risk of death due to cancer.
A Three-Genes Signature Predicting Colorectal Cancer Relapse Reveals LEMD1 Promoting CRC Cells Migration by RhoA/ROCK1 Signaling Pathway
Authors: Zhang Hui , Xu Chenxin , Jiang Feng , Feng Jifeng
Published: May 2022

Objective

Colorectal cancer (CRC) patients that experience early relapse consistently exhibit poor survival. However, no effective approach has been developed for the diagnosis and prognosis prediction of postoperative relapsed CRC.

Methods

Multiple datasets from the GEO database and TCGA database were utilized for bioinformatics analysis. WGCNA analyses and RRA analysis were performed to identify key genes. The COX/Lasso regression model was used to construct the recurrence model. Subsequent in vitro experiments further validated the potential role of the hub genes in CRC.

Results

A comprehensive analysis was performed on multiple CRC datasets and a CRC recurrence model was constructed containing LEMD1, SERPINE1, and SIAE. After further validation in two independent databases, we selected LEMD1 for in vitro experiments and found that LEMD1 could regulate CRC cell proliferation, migration, invasion, and promote EMT transition. The Rho-GTPase pulldown experiments further indicated that LEMD1 could affect RhoA activity and regulate cytoskeletal dynamics. Finally, we demonstrated that LEMD1 promoted CRC cell migration through the RhoA/ROCK1 signaling pathway.

Conclusions

In this study, a CRC relapse model consisting of LEMD1, SERPINE1, and SIAE was constructed by comprehensive analysis of multiple CRC datasets. LEMD1 could promote CRC cell migration through the RhoA/ROCK signaling pathway.
Rabbit VX2 Liver Tumor Model: A Review of Clinical, Biology, Histology, and Tumor Microenvironment Characteristics
Authors: Pascale Florentina , Pelage Jean-Pierre , Wassef Michel , Ghegediban Saïda H. , Saint-Maurice Jean-Pierre , De Baere Thierry , Denys Alban , Duran Rafael , Deschamps Frédéric , Pellerin Olivier , Maeda Noboru , Laurent Alexandre , Namur Julien
Published: May 2022

The rabbit VX2 is a large animal model of cancer used for decades by interventional radiologists to demonstrate the efficacy of various locoregional treatments against liver tumors. What do we know about this tumor in the new era of targeted therapy and immune-oncology? The present paper describes the current knowledge on the clinics, biology, histopathology, and tumor microenvironment of VX2 based on a literature review of 741 publications in the liver and in other organs. It reveals the resemblance with human cancer (anatomy, vascularity, angiogenic profile, drug sensitivity, immune microenvironment), the differences (etiology, growth rate, histology), and the questions still poorly explored (serum and tissue biomarkers, genomic alterations, immune checkpoint inhibitors efficacy).