bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterospecific Neighbor Plants Impact Root Microbiome Diversity and Molecular Function of Root Fungi
Authors: Liao Hui-Ling , Bonito Gregory , Hameed Khalid , Wu Steven H. , Chen Ko-Hsuan , Labbé Jesse , Schadt Christopher W. , Tuskan Gerald A. , Martin Francis , Kuo Alan , Barry Kerrie , Grigoriev Igor V. , Vilgalys Rytas
Published: November 2021

Within the forest community, competition and facilitation between adjacent-growing conspecific and heterospecific plants are mediated by interactions involving common mycorrhizal networks. The ability of plants to alter their neighbor’s microbiome is well documented, but the molecular biology of plant-fungal interactions during competition and facilitation has not been previously examined. We used a common soil-plant bioassay experiment to study molecular plant-microbial interactions among rhizosphere communities associated with Pinus taeda (native host) and Populus trichocarpa (non-native host). Gene expression of interacting fungal and bacterial rhizosphere communities was compared among three plant-pairs: Populus growing with Populus, Populus with Pinus, and Pinus with Pinus. Our results demonstrate that heterospecific plant partners affect the assembly of root microbiomes, including the changes in the structure of host specific community. Comparative metatranscriptomics reveals that several species of ectomycorrhizal fungi (EMF) and saprotrophic fungi exhibit different patterns of functional and regulatory gene expression with these two plant hosts. Heterospecific plants affect the transcriptional expression pattern of EMF host-specialists (e.g., Pinus-associated Suillus spp.) on both plant species, mainly including the genes involved in the transportation of amino acids, carbohydrates, and inorganic ions. Alteration of root microbiome by neighboring plants may help regulate basic plant physiological processes via modulation of molecular functions in the root microbiome.
Identification and Antifungal Mechanism of a Novel Actinobacterium Streptomyces huiliensis sp. nov. Against Fusarium oxysporum f. sp. cubense Tropical Race 4 of Banana
Authors: Qi Dengfeng , Zou Liangping , Zhou Dengbo , Zhang Miaoyi , Wei Yongzan , Zhang Lu , Xie Jianghui , Wang Wei
Published: November 2021

Banana is an important fruit crop. Fusarium wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) seriously threatens the global banana industry. It is difficult to control the disease spread using chemical measures. In addition, commercial resistant cultivars are also lacking. Biological control is considered as a promising strategy using antagonistic microbes. Actinomycetes, especially Streptomyces, are potential sources of producing novel bioactive secondary metabolites. Here, strain SCA2-4T with strong antifungal activity against Foc TR4 was isolated from the rhizospheric soil of Opuntia stricta in a dry hot valley. The morphological, physiological and chemotaxonomic characteristics of the strain were consistent with the genus Streptomyces. Based on the homology alignment and phylogenetic trees of 16S rRNA gene, the taxonomic status of strain SCA2-4T exhibited a paradoxical result and low bootstrap value using different algorithms in the MEGA software. It prompted us to further discriminate this strain from the closely related species by the multilocus sequence analysis (MLSA) using five house-keeping gene alleles (atpD, gyrB, recA, rpoB, and trpB). The MLSA trees calculated by three algorithms demonstrated that strain SCA2-4T formed a distinct clade with Streptomyces mobaraensis NBRC 13819T. The MLSA distance was above 0.007 of the species cut-off. Average nucleotide identity (ANI) values between strain SCA2-4T genome and two standard strain genomes were below 95-96% of the novel species threshold. Strain SCA2-4T was assigned to a novel species of the genus Streptomyces and named as Streptomyces huiliensis sp. nov. The sequenced complete genome of SCA2-4T encoded 51 putative biosynthetic gene clusters of secondary metabolites. Genome alignment revealed that ten gene clusters were involved in the biosynthesis of antimicrobial metabolites. It was supported that strain SCA2-4T showed strong antifungal activities against the pathogens of banana fungal diseases. Extracts abstracted from the culture filtrate of strain SCA2-4T seriously destroyed cell structure of Foc TR4 and inhibited mycelial growth and spore germination. These results implied that strain SCA2-4T could be a promising candidate for biological control of banana Fusarium wilt.
Fermented Cottonseed Meal as a Partial Replacement for Soybean Meal Could Improve the Growth Performance, Immunity and Antioxidant Properties, and Nutrient Digestibility by Altering the Gut Microbiota Profile of Weaned Piglets
Authors: Gu Xueling , Li Zhiqing , Wang Jing , Chen Jiashun , Jiang Qian , Liu Nian , Liu Xiang , Zhang Fan , Tan Bie , Li Hao , Ma Xiaokang
Published: November 2021

The study investigated the impact of fermented cottonseed meal (FCSM) on growth performance, immunity and antioxidant properties, nutrient digestibility, and gut microbiota of weaned piglets by replacing soybean meal with FCSM in the diet. The experimental piglets were fed with either the soybean meal diet (SBM group) or fermented cottonseed meal diet (FCSM group) for 14days after weaning. The digestibility of dry matter (DM), organic matter (OM), crude protein (CP), gross energy (GE), amino acids and nitrogen was higher in the FCSM diet than those in the SBM diet (p<0.05). The piglets in the FCSM group showed greater growth performance and lower diarrhea rate than those in the SBM group (p<0.05). The concentration of serum immunoglobulin G (IgG) and antioxidase, intestinal and hepatic antioxidase were increased and the concentration of malondialdehyde (MDA) in the serum was decreased in those piglets in the FCSM group compared to those piglets in the SBM group (p<0.05). The piglets in the FCSM group had a higher concentration of volatile fatty acids (VFAs) in their ileum and cecum and a higher Simpson index of ileum than piglets in the SBM group (p<0.05). The relative abundance of Lactobacillus and [Ruminococcus]_torques_group in ileum and Intestinibacter, norank_f_Muribaculaceae, unclassified_o_Lactobacillales and [Eubacterium]_coprostanoligenes_group in cecum were enhanced in piglets fed with the FCSM diet, whereas the relative abundance of Sarcina and Terrisporobacter were increased in piglets fed with the SBM diet. Overall, FCSM replacing SBM improved the growth performance, immunity and antioxidant properties, and nutrient digestibility; possibly via the alterant gut microbiota and its metabolism of weaned piglets.

Graphical Abstract

Fermented cottonseed meal as a partial replacement for soybean meal could improve the growth performance, immunity and antioxidant properties, and nutrient digestibility by altering the gut microbiota profile of weaned piglets. SBM, soybean meal; FCSM, fermented cottonseed meal.
Host Sex Steroids Interact With Virus Infection: New Insights Into Sex Disparity in Infectious Diseases
Authors: Wu Jinfeng , Zhang Lei , Wang Xing
Published: November 2021

Sex hormones are steroid hormones synthesized from the gonads of animals and tissues such as the placenta and adrenocortical reticular zone. The physiological functions of sex hormones are complex. Sex hormones are not only pathologically correlated with many diseases of the reproductive system, but are etiological factors in some viral infectious diseases, including disease caused by infections of coronaviruses, herpesviruses, hepatitis viruses, and other kinds of human viruses, which either exhibit a male propensity in clinical practice, or crosstalk with androgen receptor (AR)-related pathways in viral pathogenesis. Due to the global pandemic of coronavirus disease 2019 (COVID-19), the role of androgen/AR in viral infectious disease is highlighted again, majorly representing by the recent advances of AR-responsive gene of transmembrane protease/serine subfamily member 2 (TMPRSS2), which proteolytically activates the receptor-mediated virus entry by many coronaviruses and influenza virus, along with the role of androgen-mediated signaling for the transcription of hepatitis B virus (HBV), and the role of sex hormone responsive genes during Zika virus (ZIKV) pathogenesis, et al. Collectively, we propose to provide a comprehensive overview of the role of male sex hormones during multiple phases in the life cycle of different human viruses, which may be partly responsible for the sex-specific prevalence, severity and mortality of some diseases, therefore, may provide clues to develop more efficient prevention and treatment strategies for high-risk populations.
Molecular Investigation of Recurrent Streptococcus iniae Epizootics Affecting Coral Reef Fish on an Oceanic Island Suggests at Least Two Distinct Emergence Events
Authors: Irion Solène , Rudenko Oleksandra , Sweet Michael , Chabanet Pascale , Barnes Andrew C. , Tortosa Pablo , Séré Mathieu G.
Published: November 2021

Streptococcus iniae is an emerging zoonotic pathogen of increasing concern for aquaculture and has caused several epizootics in reef fishes from the Caribbean, the Red Sea and the Indian Ocean. To study the population structure, introduction pathways and evolution of S. iniae over recurring epizootics on Reunion Island, we developed and validated a Multi Locus Sequence Typing (MLST) panel using genomic data obtained from 89 isolates sampled during epizootics occurring over the past 40years in Australia, Asia, the United States, Israel and Reunion Island. We selected eight housekeeping loci, which resulted in the greatest variation across the main S. iniae phylogenetic clades highlighted by the whole genomic dataset. We then applied the developed MLST to investigate the origin of S. iniae responsible for four epizootics on Reunion Island, first in inland aquaculture and then on the reefs from 1996 to 2014. Results suggest at least two independent S. iniae emergence events occurred on the island. Molecular data support that the first epizootic resulted from an introduction, with inland freshwater aquaculture facilities acting as a stepping-stone. Such an event may have been facilitated by the ecological flexibility of S. iniae, able to survive in both fresh and marine waters and the ability of the pathogen to infect multiple host species. By contrast, the second epizootic was associated with a distinct ST of cosmopolitan distribution that may have emerged as a result of environment disturbance. This novel tool will be effective at investigating recurrent epizootics occurring within a given environment or country that is despite the fact that S. iniae appears to have low genetic diversity within its lineage.
Genomic Insights Into New Species of the Genus Halomicroarcula Reveals Potential for New Osmoadaptative Strategies in Halophilic Archaea
Authors: Durán-Viseras Ana , Sánchez-Porro Cristina , Ventosa Antonio
Published: November 2021

Metagenomic studies on prokaryotic diversity of hypersaline soils from the Odiel saltmarshes, South-west Spain, revealed a high proportion of genomic sequences not related to previously cultivated taxa, that might be related to haloarchaea with a high environmental and nutritional flexibility. In this study, we used a culturomics approach in order to isolate new haloarchaeal microorganisms from these hypersaline soils. Four haloarchaeal strains, designated strains F24AT, F28, F27T, and F13T, phylogenetically related to the genus Halomicroarcula, were isolated and characterized in detail. The phylogenomic tree based on the 100 orthologous single-copy genes present in the genomes of these four strains as well as those of the type strains of the species Halomicroarcula pellucida CECT 7537T, Halomicroarcula salina JCM 18369T and Halomicroarcula limicola JCM 18640T, that were determined in this study, revealed that these four new isolates clustered on three groups, with strains F24AT and F28 within a single cluster, and altogether with the species of Halomicroarcula. Additionally, Orthologous Average Nucleotide Identity (OrthoANI), digital DNA-DNA hybridization (dDDH) and Average Amino-acid Identity (AAI) values, likewise phenotypic characteristics, including their polar lipids profiles, permitted to determine that they represent three new species, for which we propose the names Halomicroarcula rubra sp. nov. (type strain F13T), Halomicroarcula nitratireducens sp. nov. (type strain F27T) and Halomicroarcula salinisoli sp. nov. (type strain F24AT). An in deep comparative genomic analysis of species of the genus Halomicroarcula, including their metabolism, their capability to biosynthesize secondary metabolites and their osmoregulatory adaptation mechanisms was carried out. Although they use a salt-in strategy, the identification of the complete pathways for the biosynthesis of the compatible solutes trehalose and glycine betaine, not identified before in any other haloarchaea, might suggest alternative osmoadaptation strategies for this group. This alternative osmoregulatory mechanism would allow this group of haloarchaea to be versatile and eco-physiologically successful in hypersaline environments and would justify the capability of the species of this genus to grow not only on environments with high salt concentrations [up to 30% (w/v) salts], but also under intermediate to low salinities.
Selection of Superior Yeast Strains for the Fermentation of Lignocellulosic Steam-Exploded Residues
Authors: Cagnin Lorenzo , Gronchi Nicoletta , Basaglia Marina , Favaro Lorenzo , Casella Sergio
Published: November 2021

The production of lignocellulosic ethanol calls for a robust fermentative yeast able to tolerate a wide range of toxic molecules that occur in the pre-treated lignocellulose. The concentration of inhibitors varies according to the composition of the lignocellulosic material and the harshness of the pre-treatment used. It follows that the versatility of the yeast should be considered when selecting a robust strain. This work aimed at the validation of seven natural Saccharomyces cerevisiae strains, previously selected for their industrial fitness, for their application in the production of lignocellulosic bioethanol. Their inhibitor resistance and fermentative performances were compared to those of the benchmark industrial yeast S. cerevisiae Ethanol Red, currently utilized in the second-generation ethanol plants. The yeast strains were characterized for their tolerance using a synthetic inhibitor mixture formulated with increasing concentrations of weak acids and furans, as well as steam-exploded lignocellulosic pre-hydrolysates, generally containing the same inhibitors. The eight non-diluted liquors have been adopted to assess yeast ability to withstand bioethanol industrial conditions. The most tolerant S. cerevisiae Fm17 strain, together with the reference Ethanol Red, was evaluated for fermentative performances in two pre-hydrolysates obtained from cardoon and common reed, chosen for their large inhibitor concentrations. S. cerevisiae Fm17 outperformed the industrial strain Ethanol Red, producing up to 18 and 39 g/L ethanol from cardoon and common reed, respectively, with ethanol yields always higher than those of the benchmark strain. This natural strain exhibits great potential to be used as superior yeast in the lignocellulosic ethanol plants.
Bactericidal Effect of Pseudomonas oryziphila sp. nov., a Novel Pseudomonas Species Against Xanthomonas oryzae Reduces Disease Severity of Bacterial Leaf Streak of Rice
Authors: Yang Ruihuan , Li Shengzhang , Li Yilang , Yan Yichao , Fang Yuan , Zou Lifang , Chen Gongyou
Published: November 2021

Pseudomonas is a diverse genus of Gammaproteobacteria with increasing novel species exhibiting versatile trains including antimicrobial and insecticidal activity, as well as plant growth–promoting, which make them well suited as biocontrol agents of some pathogens. Here we isolated strain 1257 that exhibited strong antagonistic activity against two pathovars of Xanthomonas oryzae, especially X. oryzae pv. oryzicola (Xoc) responsible for the bacterial leaf streak (BLS) in rice. The phylogenetic, genomic, physiological, and biochemical characteristics support that strain 1257 is a representative of a novel Pseudomonas species that is most closely related to the entomopathogenic bacterium Pseudomonas entomophila. We propose to name it Pseudomonas oryziphila sp. nov. Comparative genomics analyses showed that P. oryziphila 1257 possesses most of the central metabolic genes of two closely related strains P. entomophila L48 and Pseudomonas mosselii CFML 90-83, as well as a set of genes encoding the type IV pilus system, suggesting its versatile metabolism and motility properties. Some features, such as insecticidal toxins, phosphate solubilization, indole-3-acetic acid, and phenylacetic acid degradation, were disclosed. Genome-wide random mutagenesis revealed that the non-ribosomal peptide catalyzed by LgrD may be a major active compound of P. oryziphila 1257 against Xoc RS105, as well as the critical role of the carbamoyl phosphate and the pentose phosphate pathway that control the biosynthesis of this target compound. Our findings demonstrate that 1257 could effectively inhibit the growth and migration of Xoc in rice tissue to prevent the BLS disease. To our knowledge, this is the first report of a novel Pseudomonas species that displays a strong antibacterial activity against Xoc. The results suggest that the P. oryziphila strain could be a promising biological control agent for BLS.
Antibiotic Treatment, Mechanisms for Failure, and Adjunctive Therapies for Infections by Group A Streptococcus
Authors: Johnson Anders F. , LaRock Christopher N.
Published: November 2021

Group AStreptococcus(GAS;Streptococcus pyogenes) is a nearly ubiquitous human pathogen responsible for a significant global disease burden. No vaccine exists, so antibiotics are essential for effective treatment. Despite a lower incidence of antimicrobial resistance than many pathogens, GAS is still a top 10 cause of death due to infections worldwide. The morbidity and mortality are primarily a consequence of the immune sequelae and invasive infections that are difficult to treat with antibiotics. GAS has remained susceptible to penicillin and other β-lactams, despite their widespread use for 80 years. However, the failure of treatment for invasive infections with penicillin has been consistently reported since the introduction of antibiotics, and strains with reduced susceptibility to β-lactams have emerged. Furthermore, isolates responsible for outbreaks of severe infections are increasingly resistant to other antibiotics of choice, such as clindamycin and macrolides. This review focuses on the challenges in the treatment of GAS infection, the mechanisms that contribute to antibiotic failure, and adjunctive therapeutics. Further understanding of these processes will be necessary for improving the treatment of high-risk GAS infections and surveillance for non-susceptible or resistant isolates. These insights will also help guide treatments against other leading pathogens for which conventional antibiotic strategies are increasingly failing.
Application of Lab-on-Chip for Detection of Microbial Nucleic Acid in Food and Environment
Authors: Yang Liu , Yi Wei , Sun Fangfang , Xu Mengjiao , Zeng Zhan , Bi Xiaoyue , Dong Jianping , Xie Yao , Li Minghui
Published: November 2021

Various diseases caused by food-borne or environmental pathogenic microorganisms have been a persistent threat to public health and global economies. It is necessary to regularly detect microorganisms in food and environment to prevent infection of pathogenic microorganisms. However, most traditional detection methods are expensive, time-consuming, and unfeasible in practice in the absence of sophisticated instruments and trained operators. Point-of-care testing (POCT) can be used to detect microorganisms rapidly on site and greatly improve the efficiency of microbial detection. Lab-on-chip (LOC) is an emerging POCT technology with great potential by integrating most of the experimental steps carried out in the laboratory into a single monolithic device. This review will primarily focus on principles and techniques of LOC for detection of microbial nucleic acid in food and environment, including sample preparation, nucleic acid amplification and sample detection.
Cyclodextrins Exert a Ligand-like Current Inhibitory Effect on the KV1.3 Ion Channel Independent of Membrane Cholesterol Extraction
Authors: Kovacs Tamas , Sohajda Tamas , Szente Lajos , Nagy Peter , Panyi Gyorgy , Varga Zoltan , Zakany Florina
Published: November 2021

Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming water-soluble complexes with a variety of otherwise poorly soluble molecules including cholesterol and different drugs. Consistently, CDs are widely used in research and clinical practice to deplete cholesterol from cellular membranes or to increase solubility and bioavailability of different pharmaceuticals at local concentrations in the millimolar range. Effects of CDs exerted on cellular functions are generally thought to originate from reductions in cholesterol levels. Potential direct, ligand-like CD effects are largely neglected in spite of several recent studies reporting direct interaction between CDs and proteins including AMP-activated protein kinase, β-amyloid peptides, and α-synuclein. In this study, by using patch-clamp technique, time-resolved quantitation of cholesterol levels and biophysical parameters and applying cholesterol-extracting and non-cholesterol-extracting CDs at 1 and 5 mM concentrations, we provide evidence for a previously unexplored ligand-like, cholesterol-independent current inhibitory effect of CDs on KV1.3, a prototypical voltage-gated potassium channel with pathophysiological relevance in various autoimmune and neurodegenerative disorders. Our findings propose that potential direct CD effects on KV channels should be taken into consideration when interpreting functional consequences of CD treatments in both research and clinical practice. Furthermore, current-blocking effects of CDs on KV channels at therapeutically relevant concentrations might contribute to additional beneficial or adverse effects during their therapeutic applications.
FN3 Domain Displaying Double Epitopes: A Cost-Effective Strategy for Producing Substitute Antigens
Authors: Ruan Yao , Chao Shuangying , Hu Xuejun , Lu Longzhen , Lin Yue , Wang Qian , Zheng Yang , Li Junming , Ding Ning
Published: November 2021

Construction of substitute antigens based on alternative scaffold proteins is a promising strategy in bioassay technology. In this study, we proposed a strategy for constructing substitute antigens derived from 10th human fibronectin type III (FN3) using two peptide epitopes of terminal pro-brain natriuretic peptide (NT-proBNP) as an example. The base sequences encoding the two antigenic epitopes of NT-proBNP were recombined into the FG loop region and the C-terminus of FN3, fused by 4 GS or polyN linker. The fusion proteins (named FN3-epitopes-4GS and FN3-epitopes-polyN, respectively) were expressed and purified cost-effectively using an Escherichia coli expression system. The immunoreactivity of recombinant substitutes was preliminarily confirmed by western blot analysis using epitope-specific antibodies. The sandwich enzyme-linked immunosorbent assay demonstrated that either FN3-epitopes-polyN or FN3-epitopes-4GS was highly sensitive, and FN3-epitopes-polyN exhibited better kinetics to specific antibodies than FN3-epitopes-4GS, showing a linear dose-response relationship in the concentration range of 0.06–12.85 ng/ml, which suggest that the polyN linker was more suitable for constructing the FN3-based substitute antigens compared to the 4 GS linker. Furthermore, the serum stability test and differential scanning calorimetry analysis showed that the recombinant FN3-epitopes-polyN maintained the original stability of FN3. Therefore, it was confirmed that FN3 could be engineered to construct a stable biomacromolecular substitute for displaying double epitopes of antigen proteins, such as NT-proBNP. In summary, a cost-effective strategy to produce NT-proBNP substitute antigens with good immunoreactivity and physicochemical stability was established in this work, which may provide potential uses for the production of other substitute antigens in the future.
Utilization of Human Induced Pluripotent Stem Cells-Derived In vitro Models for the Future Study of Sex Differences in Alzheimer’s Disease
Authors: Supakul Sopak , Okano Hideyuki , Maeda Sumihiro
Published: November 2021

Alzheimer’s disease (AD) is an aging-dependent neurodegenerative disease that impairs cognitive function. Although the main pathologies of AD are the aggregation of amyloid-beta (Aβ) and phosphorylated Tau protein, the mechanisms that lead to these pathologies and their effects are believed to be heterogeneous among patients. Many epidemiological studies have suggested that sex is involved in disease prevalence and progression. The reduction of sex hormones contributes to the pathogenesis of AD, especially in females, suggesting that the supplementation of sex hormones could be a therapeutic intervention for AD. However, interventional studies have revealed that hormone therapy is beneficial under limited conditions in certain populations with specific administration methods. Thus, this suggests the importance of identifying crucial factors that determine hormonal effects in patients with AD. Based on these factors, it is necessary to decide which patients will receive the intervention before starting it. However, the long observational period and many uncontrollable environmental factors in clinical trials made it difficult to identify such factors, except for the APOE ε4 allele. Induced pluripotent stem cells (iPSCs) derived from patients can differentiate into neurons and recapitulate some aspects of AD pathogenesis. This in vitro model allows us to control non-cell autonomous factors, including the amount of Aβ aggregates and sex hormones. Hence, iPSCs provide opportunities to investigate sex-dependent pathogenesis and predict a suitable population for clinical trials of hormone treatment.
Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity
Authors: Ellis Seneca N. , Honeycutt Jennifer A.
Published: November 2021

The early life environment markedly influences brain and behavioral development, with adverse experiences associated with increased risk of anxiety and depressive phenotypes, particularly in females. Indeed, early life adversity (ELA) in humans (i.e., caregiver deprivation, maltreatment) and rodents (i.e., maternal separation, resource scarcity) is associated with sex-specific emergence of anxious and depressive behaviors. Although these disorders show clear sex differences in humans, little attention has been paid toward evaluating sex as a biological variable in models of affective dysfunction; however, recent rodent work suggests sex-specific effects. Two widely used rodent models of ELA approximate caregiver deprivation (i.e., maternal separation) and resource scarcity (i.e., limited bedding). While these approaches model aspects of ELA experienced in humans, they span different portions of the pre-weaning developmental period and may therefore differentially contribute to underlying mechanistic risk. This is borne out in the literature, where evidence suggests differences in trajectories of behavior depending on the type of ELA and/or sex; however, the neural underpinning of these differences is not well understood. Because anxiety and depression are thought to involve dysregulation in the balance of excitatory and inhibitory signaling in ELA-vulnerable brain regions (e.g., prefrontal cortex, amygdala, hippocampus), outcomes are likely driven by alterations in local and/or circuit-specific inhibitory activity. The most abundant GABAergic subtypes in the brain, accounting for approximately 40% of inhibitory neurons, contain the calcium-binding protein Parvalbumin (PV). As PV-expressing neurons have perisomatic and proximal dendritic targets on pyramidal neurons, they are well-positioned to regulate excitatory/inhibitory balance. Recent evidence suggests that PV outcomes following ELA are sex, age, and region-specific and may be influenced by the type and timing of ELA. Here, we suggest the possibility of a combined role of PV and sex hormones driving differences in behavioral outcomes associated with affective dysfunction following ELA. This review evaluates the literature across models of ELA to characterize neural (PV) and behavioral (anxiety- and depressive-like) outcomes as a function of sex and age. Additionally, we detail a putative mechanistic role of PV on ELA-related outcomes and discuss evidence suggesting hormone influences on PV expression/function which may help to explain sex differences in ELA outcomes.
The Effect of a Combined Ganciclovir, Methylprednisolone, and Immunoglobulin Regimen on Survival and Functional Outcomes in Patients With Japanese Encephalitis
Authors: Miao Wang , Guo Junshuang , Zhang Shuyu , Shen Nannan , Shang Xiaoping , Liu Furong , Lu Warren , Xu Jianghai , Teng Junfang
Published: November 2021

Objective: There is currently no effective treatment for Japanese encephalitis, which has a high rate of morbidity and mortality. This study assessed the effectiveness of a ganciclovir, methylprednisolone, and immunoglobulin combination (TAGMIC) therapy in decreasing cognitive impairment and mortality among patients with Japanese encephalitis.

Methods: We retrospectively assessed the clinical data of 31 patients diagnosed with Japanese encephalitis, who were admitted to an intensive care unit. Patients were divided into the TAGMIC and non-TAGMIC group according to their treatment regime. We compared the 60-day, 6-month, and overall mortality and survival curves between groups. We also compared Barthel Index scores, Montreal Cognitive Assessment (MoCA) scores, and diffusion tensor imaging (DTI) results.

Results: There was no significant difference in the 30-day mortality rate or Kaplan–Meier survival curve between groups. The 60-day, 6-month, and overall mortality rates in the TAGMIC group were significantly reduced (P = 0.043, P = 0.018, and P = 0.018, respectively) compared with the non-TAGMIC group (0, 0, 0 vs. 31.25, 37.5, 37.5%, respectively). The 60-day, 6-month, and overall Kaplan–Meier survival curves were significantly different between groups (P = 0.020, P = 0.009, P = 0.009, respectively). There was no significant difference in the Barthel Index scores of surviving patients. Among the five patients who underwent MoCA and DTI, four had a score of 0/5 for delayed recall (no cue), while the remaining patient had a score of 2/5. All five patients were able to achieve a score of 5/5 with classification and multiple-choice prompts, and had sparse or broken corpus callosum (or other) fibre bundles.

Conclusion: TAGMIC treatment can reduce mortality due to severe Japanese encephalitis. The memory loss of surviving patients is mainly due to a disorder of the memory retrieval process, which may be related to the breakage of related fibre bundles.
The Onset of Interictal Spike-Related Ripples Facilitates Detection of the Epileptogenic Zone
Authors: Numata-Uematsu Yurika , Uematsu Mitsugu , Sakuraba Rie , Iwasaki Masaki , Osawa Shinichiro , Jin Kazutaka , Nakasato Nobukazu , Kure Shigeo
Published: November 2021

Objective: Accurate estimation of the epileptogenic zone (EZ) is essential for favorable outcomes in epilepsy surgery. Conventional ictal electrocorticography (ECoG) onset is generally used to detect the EZ but is insufficient in achieving seizure-free outcomes. By contrast, high-frequency oscillations (HFOs) could be useful markers of the EZ. Hence, we aimed to detect the EZ using interictal spikes and investigated whether the onset area of interictal spike-related HFOs was within the EZ.

Methods: The EZ is considered to be included in the resection area among patients with seizure-free outcomes after surgery. Using a complex demodulation technique, we developed a method to determine the onset channels of interictal spike-related ripples (HFOs of 80–200 Hz) and investigated whether they are within the resection area.

Results: We retrospectively examined 12 serial patients who achieved seizure-free status after focal resection surgery. Using the method that we developed, we determined the onset channels of interictal spike-related ripples and found that for all 12 patients, they were among the resection channels. The onset frequencies of ripples were in the range of 80–150 Hz. However, the ictal onset channels (evaluated based on ictal ECoG patterns) and ripple onset channels coincided in only 3 of 12 patients.

Conclusions: Determining the onset area of interictal spike-related ripples could facilitate EZ estimation. This simple method that utilizes interictal ECoG may aid in preoperative evaluation and improve epilepsy surgery outcomes.
The Role of Continuous Theta Burst TMS in the Neurorehabilitation of Subacute Stroke Patients: A Placebo-Controlled Study
Authors: Dionísio Ana , Gouveia Rita , Castelhano João , Duarte Isabel Catarina , Santo Gustavo C. , Sargento-Freitas João , Duecker Felix , Castelo-Branco Miguel
Published: November 2021

Objectives: Transcranial magnetic stimulation, in particular continuous theta burst (cTBS), has been proposed for stroke rehabilitation, based on the concept that inhibition of the healthy hemisphere helps promote the recovery of the lesioned one. We aimed to study its effects on cortical excitability, oscillatory patterns, and motor function, the main aim being to identify potentially beneficial neurophysiological effects.

Materials and Methods: We applied randomized real or placebo stimulation over the unaffected primary motor cortex of 10 subacute (7 ± 3 days) post-stroke patients. Neurophysiological measurements were performed using electroencephalography and electromyography. Motor function was assessed with the Wolf Motor Function Test. We performed a repeated measure study with the recordings taken pre-, post-cTBS, and at 3 months' follow-up.

Results: We investigated changes in motor rhythms during arm elevation and thumb opposition tasks and found significant changes in beta power of the affected thumb's opposition, specifically after real cTBS. Our results are consistent with an excitatory response (increase in event-related desynchronization) in the sensorimotor cortical areas of the affected hemisphere, after stimulation. Neither peak-to-peak amplitude of motor-evoked potentials nor motor performance were significantly altered.

Conclusions: Consistently with the theoretical prediction, this contralateral inhibitory stimulation paradigm changes neurophysiology, leading to a significant excitatory impact on the cortical oscillatory patterns of the contralateral hemisphere. These proof-of-concept results provide evidence for the potential role of continuous TBS in the neurorehabilitation of post-stroke patients. We suggest that these changes in ERS/ERD patterns should be further explored in future phase IIb/phase III clinical trials, in larger samples of poststroke patients.
Cochlear Implants in Single-Sided Deafness. Comparison Between Children and Adult Populations With Post-lingually Acquired Severe to Profound Hearing Loss
Authors: Falcón Benítez Nadia , Falcón González Juan Carlos , Ramos Macías Ángel , Borkoski Barreiro Silvia , Ramos de Miguel Ángel
Published: November 2021

Objective: To determine audiological and clinical results of cochlear implantation (CI) comparing two populations with single-sided deafness (SSD): post-lingually deaf children between 6 and 12 years of age, and post-lingually deaf adults, in order to evaluate the effect of CI in different age groups.

Design: Retrospective case review.

Setting: Tertiary clinic.

Patients and Method: Twenty-three children and twenty-one adult patients that were candidates for CI with single-side deafness were included. In all cases we evaluate: Speech perception thresholds; disyllabic words test (65 dB SPL) were performed in the modalities S0–SCI–SNH and Auditory Lateralization Test. The Speech, Spatial, and Qualities of Hearing Scale (SSQ) questionnaire was also used. All results were obtained after 12 months of CI activation.

Results: In children, the most common etiology was idiopathic sensory-neural hearing loss. They showed positive results in the Auditory Lateralization Test. In the Speech Test, word recognition in noise improved from 2% preoperatively to 61.1% at a mean follow-up of 1 year (S0 condition) in children [test with signal in CI side 60% and signal normal hearing side (plugged) 31%]. The processor was used for >12 h in all cases. With respect to the SSQ questionnaire, parents were more satisfied within the postoperative period than within the preoperative period. For adults, the most common etiology was idiopathic sudden sensorineural hearing loss (SNHL). Positive results in the Auditory Lateralization Test were found. With respect to the Speech Test in quiet conditions: Word recognition in noise improved from 5.7% preoperatively to 71.8% at a mean follow-up of 1 year [test with signal in CI side 68% and signal normal hearing side (plugged) 41%]. The processor was used for >12 h. In the SSQ questionnaire, the post-operative results showed a beneficial effect of the CI. No adverse events were reported during the study period. No differences were found between children and adults in all tests in this study.

Conclusions: Cochlear implantation in post-lingually deaf adults and children with SSD can achieve a speech perception outcome comparable with CI in conventional candidates. Improvements in spatial hearing were also observed. Careful patient selection and counseling regarding potential benefits are important to optimize outcomes.
Perspective on Vision Science-Informed Interventions for Central Vision Loss
Authors: Maniglia Marcello , Visscher Kristina M. , Seitz Aaron R.
Published: November 2021

Pathologies affecting central vision, and macular degeneration (MD) in particular, represent a growing health concern worldwide, and the leading cause of blindness in the Western World. To cope with the loss of central vision, MD patients often develop compensatory strategies, such as the adoption of a Preferred Retinal Locus (PRL), which they use as a substitute fovea. However, visual acuity and fixation stability in the visual periphery are poorer, leaving many MD patients struggling with tasks such as reading and recognizing faces. Current non-invasive rehabilitative interventions are usually of two types: oculomotor, aiming at training eye movements or teaching patients to use or develop a PRL, or perceptual, with the goal of improving visual abilities in the PRL. These training protocols are usually tested over a series of outcome assessments mainly measuring low-level visual abilities (visual acuity, contrast sensitivity) and reading. However, extant approaches lead to mixed success, and in general have exhibited large individual differences. Recent breakthroughs in vision science have shown that loss of central vision affects not only low-level visual abilities and oculomotor mechanisms, but also higher-level attentional and cognitive processes. We suggest that effective interventions for rehabilitation after central vision loss should then not only integrate low-level vision and oculomotor training, but also take into account higher level attentional and cognitive mechanisms.
Vestibular Morphological Asymmetry Associated With Motion Sickness Susceptibility
Authors: Harada Takumi , Sugawara Tomoko , Ito Taeko , Wada Yoshiro , Fukunaga Masaki , Sadato Norihiro , Larroque Stephen K. , Demertzi Athena , Laureys Steven , Sakai Hiroyuki
Published: November 2021

Sensory conflicts leading to motion sickness can occur not only between but also within sensory modalities. The vestibular organs are located in both left and right inner ears, and their misalignment can be a source of self-motion related sensory conflicts. In the current study, using inner ear magnetic resonance imaging, we examined whether morphological asymmetry of the bilateral vestibular organs was associated with motion sickness susceptibility. The results showed a larger position asymmetry of bilateral vestibular organs in individuals with high rather than low susceptibility. In addition, vestibular position asymmetry was associated with reciprocal interaction (negative resting state functional connectivity) between vestibular and visuocortical regions in lowly, but not highly, susceptible individuals. In conclusion, these findings suggest that vestibular morphological asymmetry can be a source of sensory conflicts in individuals with dysfunctional reciprocal visuo-vestibular interactions, a putative neural mechanism for resolving sensory conflicts.
Specificity of Saliva Esterases by Wine Carboxylic Esters and Inhibition by Wine Phenolic Compounds Under Simulated Oral Conditions
Authors: Pérez-Jiménez María , Muñoz-González Carolina , Pozo-Bayón María Ángeles
Published: November 2021

The specificity of human esterase activity (EA) from the stimulated (SS) and non-stimulated (NSS) saliva toward different typical wine odorant carboxylic esters and its inhibition by the wine phenolic compounds has been evaluated. For the specificity, six p-nitrophenyl linked esters with different carbon chain lengths (from 2 to 12 carbons) were employed. The five single phenolic compounds (catechin, quercetin, kaempferol, myricetin, and resveratrol) at typical wine concentrations were assayed in the salivary EA inhibition study. Additionally, the inhibition exerted by the mixtures of wine polyphenols was evaluated using four commercial phenolic extracts [a grape seed extract (GSE), the monomers and oligomer fraction of the GSE, and a red wine extract (RWE)]. Finally, the saliva EA under the wine consumption conditions (pH = 5 and 11.3% ethanol) was evaluated. The results showed a higher EA in SS than NSS. It was also shown that the EA was higher toward the smaller than bigger esters regardless of the saliva types (SS or NSS). However, the inhibition exerted on saliva EA by the individual and mixtures of phenolic compounds was proven. Catechin was the phenolic compound that mostly inhibited saliva EA, while resveratrol showed the lowest EA inhibition. This inhibition was mainly related to the concentration of the phenolic compounds, but also with its structure. Finally, under simulated wine consumption, a decrease in EA was produced, which was mainly provoked by the decrease in the salivary pH. Nonetheless, since salivary pH recovers a few seconds after wine consumption, saliva EA might be relevant for the long-lasting perception of wine esters.
Case Report: Kampo Medicine for Non-tuberculous Mycobacterium Pulmonary Disease
Authors: Suzuki Tomoko , Uneda Kazushi , Aoyagi Ryutaro , Kobayashi Takehito , Mitsuma Tadamichi , Nakamoto Hidetomo
Published: November 2021

Background: While the number of pulmonary tuberculosis cases has decreased, increase in non-tuberculous mycobacterium pulmonary disease (NTM-PD) is a global problem. Guideline-based therapy for NTM-PD sometimes causes complications that prevent treatment completion, and there are many cases of relapse even if the treatment can be completed. In addition to antibacterial treatment, care of host risk factors, such as aging, lean physique and immunosuppressive state, is also very important for the management of NTM-PD. In Japan, Kampo medicine, a traditional Japanese herbal formulation, used alone or in combination with standard multidrug therapy for NTM-PD, has been found to be effective for such cases.

Case Presentation: A 77-year-old lean woman had been diagnosed with Mycobacterium intracellulare pulmonary infection 6 years earlier, and had received the standard multidrug treatment 5 years later at a former hospital due to worsening of her symptoms of cough, breathlessness and hemoptysis. However, the treatment was discontinued within a year due to the development of adverse events. She refused the guideline-based antibacterial treatment, and asked for Kampo medicine instead. Bukuryoshigyakuto was subsequently prescribed, which led to cough and sputum, especially hemosputum, being well controlled. With 3 years of Kampo medicine treatment, she gained weight and her hemosputum disappeared. High-resolution computed tomography images showed improvement in her lung condition, and her sputum smear culture was negative for acid-fast bacillus.

Conclusion: Various kinds of Kampo medicines have been used empirically for NTM-PD in Japan. A literature review from 1992 to 2020 showed that hozais, in particular, seem to be key drugs for the treatment of host NTM-PD risk factors. Kampo medicines can contribute to comprehensive treatment for NTM-PD management that does not rely solely on antibacterial drugs.
The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence
Authors: Yang Jiqing , Xiong Pu , Bai Ling , Zhang Zunyue , Zhou Yong , Chen Cheng , Xie Zhenrong , Xu Yu , Chen Minghui , Wang Huawei , Zhu Mei , Yu Juehua , Wang Kunhua
Published: November 2021

The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.
KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway
Authors: Gao Lin , Zhao Ru , Liu Junmei , Zhang Wenbo , Sun Feifei , Yin Qianshuo , Wang Xin , Wang Meng , Feng Tingting , Qin Yiming , Cai Wenjie , Li Qianni , Dong Hanchen , Chen Xueqing , Xiong Xueting , Liu Hui , Hu Jing , Chen Weiwen , Han Bo
Published: November 2021

Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.