bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies targeting hemagglutinin cocktail as a potential universal influenza vaccine
Authors: Liu Xuejie , Zhao Tianyi , Wang Liangliang , Li Minchao , Sun Caijun , Shu Yuelong
Published: September 2022

Vaccination is the most effective means of protecting people from influenza virus infection. The effectiveness of existing vaccines is very limited due to antigenic drift of the influenza virus. Therefore, there is a requirement to develop a universal vaccine that provides broad and long-lasting protection against influenza. CD8+ T-cell response played a vital role in controlling influenza virus infection, reducing viral load, and less clinical syndrome. In this study, we optimized the HA sequences of human seasonal influenza viruses (H1N1, H3N2, Victoria, and Yamagata) by designing multivalent vaccine antigen sets using a mosaic vaccine design strategy and genetic algorithms, and designed an HA mosaic cocktail containing the most potential CTL epitopes of seasonal influenza viruses. We then tested the recombinant mosaic antigen, which has a significant number of potential T-cell epitopes. Results from genetic evolutionary analyses and 3D structural simulations demonstrated its potential to be an effective immunogen. In addition, we have modified an existing neutralizing antibody-based seasonal influenza virus vaccine to include a component that activates cross-protective T cells, which would provide an attractive strategy for improving human protection against seasonal influenza virus drift and mutation and provide an idea for the development of a rationally designed influenza vaccine targeting T lymphocyte immunity.
Effects of dazomet combined with Rhodopsesudomonas palustris PSB-06 on root-knot nematode, Meloidogyne incognita infecting ginger and soil microorganisms diversity
Authors: Wang Dongwei , Wang Jian , Su Pin , Dai Jianping , Tan Xinqiu , Zhang Deyong , Liu Yong , Cheng Feixue
Published: September 2022

Root-knot nematode, Meloidogyne incognita is one of the most important nematodes affecting ginger crop. Rhodopseudomonas palustris PSB-06, as effective microbial fertilizer in increasing plant growth and suppressing soil-borne disease of many crops has been reported. The combination of R. palustris PSB-06 and dazomet treatments had been proved to inhibit root-knot nematode on ginger and increase ginger yield in our preliminary study. The field experiments were conducted to elucidate the reasons behind this finding, and followed by next-generation sequencing to determine the microbial population structures in ginger root rhizosphere. The results showed that combination of R. palustris PSB-06 and dazomet treatment had a synergetic effect by achieving of 80.00% reduction in root-knot nematode numbers less than soil without treatment, and also could increase 37.37% of ginger yield through increasing the contents of chlorophyll and total protein in ginger leaves. Microbiota composition and alpha diversity varied with treatments and growth stages, soil bacterial diversity rapidly increased after planting ginger. In addition, the combined treatment could increase diversity and community composition of probiotic bacteria, and decrease those of soil-borne pathogenic fungi comparing to the soil treated with dazomet alone. Meanwhile, it could also effectively increase soil organic matter, available phosphorus and available potassium. Analysis of correlation between soil microorganisms and physicochemical properties indicated that the soil pH value and available phosphorus content were important factors that could affect soil microorganisms structure at the harvest stage. The bacterial family was more closely correlated with the soil physicochemical properties than the fungal family. Therefore, the combination of R. palustris PSB-06 and dazomet was considered as an effective method to control root-knot nematode disease and improve ginger soil conditions.
Differential assembly of root-associated bacterial and fungal communities of a dual transgenic insect-resistant maize line at different host niches and different growth stages
Authors: Wen Zhongling , Yao Weixuan , Han Mi , Xu Xinhong , Wu Fengci , Yang Minkai , Fazal Aliya , Yin Tongming , Qi Jinliang , Lu Guihua , Yang Rongwu , Song Xinyuan , Yang Yonghua
Published: September 2022

Transgenic technology has been widely applied to crop development, with genetically modified (GM) maize being the world’s second-largest GM crop. Despite the fact that rhizosphere bacterial and fungal populations are critical regulators of plant performance, few studies have evaluated the influence of GM maize on these communities. Plant materials used in this study included the control maize line B73 and themcry1Abandmcry2Abdual transgenic insect-resistant maize line 2A-7. The plants and soils samples were sampled at three growth stages (jointing, flowering, and maturing stages), and the sampling compartments from the outside to the inside of the root are surrounding soil (SS), rhizospheric soil (RS), and intact root (RT), respectively. In this study, the results of alpha diversity revealed that from the outside to the inside of the root, the community richness and diversity declined while community coverage increased. Morever, the different host niches of maize rhizosphere and maize development stages influenced beta diversity according to statistical analysis. The GM maize line 2A-7 had no significant influence on the composition of microbial communities when compared to B73. Compared to RS and SS, the host niche RT tended to deplete Chloroflexi, Gemmatimonadetes and Mortierellomycota at phylum level. Nitrogen-fixation bacteriaPseudomonas,Herbaspirillum huttiense,Rhizobium leguminosarum, andSphingomonas azotifigenswere found to be enriched in the niche RT in comparison to RS and SS, whilstBacilluswas found to be increased andStenotrophomonaswas found to be decreased at the maturing stage as compared to jointing and flowering stages. The nitrogen fixation protein FixH (clusters of orthologous groups, COG5456), was found to be abundant in RT. Furthermore, the pathogen fungus that causes maize stalk rot,Gaeumannomyces radicicola, was found to be abundant in RT, while the beneficial fungusMortierella hyalinawas found to be depleted in RT. Lastly, the abundance ofG. radicicolagradually increased during the development of maize. In conclusion, the host niches throughout the soil-plant continuum rather than the Bt insect-resistant gene or Bt protein secretion were primarily responsible for the differential assembly of root-associated microbial communities in GM maize, which provides the theoretical basis for ecological agriculture.
Mixed infection of an emaravirus, a crinivirus, and a begomovirus in Pueraria lobata (Willd) Ohwi
Authors: Liang Xiaofei , Mei Shiqiang , Yu Haodong , Zhang Song , Wu Jiaxing , Cao Mengji
Published: September 2022

Pueraria lobata (Willd) (Pueraria montana var. lobata (Willd.) Maesen & S. M. Almeida ex Sanjappa & Predeep) is an important herbal medicine used in many countries. In P. lobata plants showing symptoms of mosaic, yellow spots, and mottling, mixed infection of new viruses provisionally named Pueraria lobata-associated emaravirus (PloAEV, genus Emaravirus), Pueraria lobata-associated crinivirus (PloACV, genus Crinivirus), and isolate CQ of the previously reported kudzu mosaic virus (KuMV-CQ, genus Begomovirus) was confirmed through high-throughput sequencing. PloAEV has five RNA segments, encoding a putative RNA-dependent RNA polymerase, glycoprotein precursor, nucleocapsid protein, movement protein, and P5, respectively. PloACV has two RNA segments, encoding 11 putative proteins. Only PloAEV could be mechanically transmitted from mixed infected symptomatic kudzu to Nicotiana benthamiana plants. All three viruses were detected in 35 symptomatic samples collected from five different growing areas, whereas no viruses were detected in 21 non-symptomatic plants, suggesting a high association between these three viruses. Thus, this study provides new knowledge on the diversity and molecular characteristics of viruses in P. lobata plants affected by the viral disease.
Microorganisms associated with Sporobolus anglicus, an invasive dimethylsulfoniopropionate producing salt marsh plant, are an unrecognized sink for dimethylsulfide
Authors: Kröber Eileen , Mankowski Anna , Schäfer Hendrik
Published: September 2022

Background

Saltmarshes are hotspots of organosulfur compound cycling due to production of dimethylsulfoniopropionate (DMSP) by benthic microorganisms, macroalgae, and saltmarsh vegetation. Degradation of DMSP is a source of dimethylsulfide (DMS), an important precursor for formation of secondary organic aerosol. Microorganisms degrading DMS play a role in controlling the amount of DMS available for emission into the atmosphere. Previous work has implicated sediment microbial populations as a major sink for DMS. Here, we show that Sporobolus anglicus (previously known as Spartina anglica), a widely distributed saltmarsh plant, is colonized by DMS-degrading microorganisms.

Methods

Dimethylsulfide degradation potential was assessed by gas chromatography and 13C-DMS stable isotope probing, microbial community diversity and functional genetic potential in phyllosphere and rhizosphere samples was assessed by high-throughput sequencing of 16S rRNA gene amplicons, cloning and sequencing of methanethiol oxidase genes, and by metagenomic analysis of phyllosphere microbial communities.

Results

The DMS degradation potential of microbial communities recovered from phyllosphere and rhizosphere samples was similar. Active DMS-degraders were identified by 13C-DMS stable isotope probing and included populations related to Methylophaga and other Piscirickettsiaceae in rhizosphere samples. DMS-degraders in the phyllosphere included Xanthomonadaceae and Halothiobacillaceae. The diversity in sediment samples of the methanethiol oxidase (mtoX) gene, a marker for metabolism of methanethiol during DMS and DMSP degradation, was similar to previously detected saltmarsh mtoX, including those of Methylophaga and Methylococcaeae. Phyllosphere mtoX genes were distinct from sediment mtoX and did not include close relatives of cultivated bacteria. Microbial diversity in the phyllosphere of S. anglicus was distinct compared to those of model plants such as rice, soybean, clover and Arabidopsis and showed a dominance of Gammaproteobacteria rather than Alphaproteobacteria.

Conclusion

The potential for microbial DMS degradation in the phyllosphere and rhizosphere of Sporobolus anglicus suggest that DMS cycling in saltmarshes is more complex than previously recognised and calls for a more detailed assessment of how aboveground activities affect fluxes of DMS.
Virome of Pseudostellaria heterophylla: Identification and characterization of three novel carlaviruses and one novel amalgavirus associated with viral diseases of Pseudostellaria heterophylla
Authors: Li Yong , Liu Sai , Guo Kun , Ding Wanlong , Wang Rong
Published: September 2022

Pseudostellaria heterophylla is a traditional Chinese herbal medicine, which has been cultivated for hundreds of years. Viral diseases of P. heterophylla occur widely and limit the yield and quality of this medicinal plant. In this study, five leaf samples of P. heterophylla with typical viral symptoms were collected from four main producing regions that are distributed in Fujian, Guizhou, and Anhui Provinces in China and analyzed by next-generation sequencing. Comprehensive bioinformatics analyses revealed that nine viruses in five genera Carlavirus, Potyvirus, Fabavirus, Cucumovirus, and Amalgavirus infected P. heterophylla. Among these viruses, three novel and two known carlaviruses, tentatively designated Pseudostellaria heterophylla carlavirus 1, 2, and 3 (PhCV1, PhCV2, and PhCV3), Jasmine virus C isolate Ph (Ph-JVC) and Stevia carlavirus 1 isolate Ph (Ph-StCV1), respectively, were first identified in P. heterophylla. PhCV1-3 share a similar genomic organization and clear sequence homology with members in the genus Carlavirus and could potentially be classified as new species of this genus. One novel amalgavirus, tentatively designated P. heterophylla amalgavirus 1 (PhAV1), was first identified in P. heterophylla. It had a typical genomic organization of the genus Amalgavirus. In PhAV1, the + 1 programmed ribosomal frameshifting, which is prevalent in most amalgaviruses, was identified and used in the expression of RNA-dependent RNA polymerase (RdRp). Combined with a phylogenetic analysis, PhAV1 could potentially be classified as new species of the genus Amalgavirus. In addition, multiple Broad bean wilt virus 2 (BBWV2) variants, Turnip mosaic virus (TuMV), and Cucumber mosaic virus (CMV), which have been reported in P. heterophylla, were also detected in this study. The distribution of PhCV1-3, Ph-JVC, Ph-StCV1, TuMV, BBWV2, and CMV in four production regions in Fujian, Guizhou, and Anhui Provinces was determined. This study increased our understanding of P. heterophylla virome and provided valuable information for the development of a molecular diagnostic technique and control of viral diseases in P. heterophylla.
Dissemination and prevalence of plasmid-mediated high-level tigecycline resistance gene tet (X4)
Authors: Zhang Shaqiu , Wen Jinfeng , Wang Yuwei , Wang Mingshu , Jia Renyong , Chen Shun , Liu Mafeng , Zhu Dekang , Zhao Xinxin , Wu Ying , Yang Qiao , Huang Juan , Ou Xumin , Mao Sai , Gao Qun , Sun Di , Tian Bin , Cheng Anchun
Published: September 2022

With the large-scale use of antibiotics, antibiotic resistant bacteria (ARB) continue to rise, and antibiotic resistance genes (ARGs) are regarded as emerging environmental pollutants. The new tetracycline-class antibiotic, tigecycline is the last resort for treating multidrug-resistant (MDR) bacteria. Plasmid-mediated horizontal transfer enables the sharing of genetic information among different bacteria. The tigecycline resistance gene tet(X) threatens the efficacy of tigecycline, and the adjacent ISCR2 or IS26 are often detected upstream and downstream of the tet(X) gene, which may play a crucial driving role in the transmission of the tet(X) gene. Since the first discovery of the plasmid-mediated high-level tigecycline resistance gene tet(X4) in China in 2019, the tet(X) genes, especially tet(X4), have been reported within various reservoirs worldwide, such as ducks, geese, migratory birds, chickens, pigs, cattle, aquatic animals, agricultural field, meat, and humans. Further, our current researches also mentioned viruses as novel environmental reservoirs of antibiotic resistance, which will probably become a focus of studying the transmission of ARGs. Overall, this article mainly aims to discuss the current status of plasmid-mediated transmission of different tet(X) genes, in particular tet(X4), as environmental pollutants, which will risk to public health for the “One Health” concept.
Rhamnolipids and fengycins, very promising amphiphilic antifungal compounds from bacteria secretomes, act on Sclerotiniaceae fungi through different mechanisms
Authors: Botcazon Camille , Bergia Thomas , Lecouturier Didier , Dupuis Chloé , Rochex Alice , Acket Sébastien , Nicot Philippe , Leclère Valérie , Sarazin Catherine , Rippa Sonia
Published: September 2022

Rhamnolipids (RLs) and fengycins (FGs) are amphiphilic lipid compounds from bacteria secretomes proposed to replace synthetic pesticides for crop protection. They both display plant defense triggering properties and direct antimicrobial activities. In particular, they have well reported antifungal effects against phytopathogenic fungi. RLs and FGs are considered to act through a direct interaction with membrane lipids and a destabilization of microorganism plasma membrane, thereby limiting the risk of resistance emergence. The main objective of this work was to gain insights in the antimycelial mode of action of these metabolites to promote them as environment and human health friendly biocontrol solutions. Their biocidal effects were studied on two Sclerotiniaceae fungi responsible for diseases in numerous plant species worldwide. We show here that different strains of Botrytis cinerea and Sclerotinia sclerotiorum have opposite sensitivities to RLs and FGs on plate experiments. Overall, B. cinerea is more sensitive to FGs while S. sclerotiorum is more sensitive to RLs. Electron microscopy observations demonstrated that RLs induce mycelial destructuring by asperities emergence and hyphal fusions whereas FGs promote swelling and formation of vesicle-like structures due to vacuole fusions and autophagy. Permeability studies, phosphatidylserine externalization and reactive oxygen species production assessments showed a programmed cell death triggering by RLs at medium concentrations (until 50 μg mL−1) and necrosis characteristics at higher concentration. Programmed cell death was always observed on hyphae treated with FGs. Quantifications of mycelial ergosterol content indicated that a higher ergosterol rate in S. sclerotiorum correlates with increasing sensitivity to RLs. Oppositely, a lower ergosterol rate in B. cinerea correlates with increasing sensitivity to FGs, which was confirmed by ergosterol biosynthesis inhibition with tebuconazole. This gain of knowledge will help to better understand the mode of action of RLs and FGs to fight specific plant fungal diseases.
Characterization of cervical canal and vaginal bacteria in pregnant women with cervical incompetence
Authors: Sun Meiguo , Geng Huiwu , Bai Jingjing , Feng Jiahui , Xu Na , Liu Yunlong , Liu Xiaoying , Liu Gang
Published: September 2022

Vaginal and cervical canal bacteria are associated with women’s health and pregnancy outcomes. Here, we compared their composition and characteristics in 37 reproductive-aged Chinese women including 24 pregnant women with cervical incompetence (vaginal and cervical canal bacteria formed Groups A and B, respectively) and 13 healthy pregnant women (vaginal and cervical canal bacteria formed Groups C and D, respectively) using high-throughput sequencing of the V4 region of 16S rRNA gene. The results of alpha and beta diversity analysis, respectively, indicated no statistical differences between Groups A and B (p = 0.32, 0.06), nor Groups B and D (p = 0.69, 0.74); however, differences were found between Groups C and D (p = 0.02, 0.01) and between Groups A and C (p = 0.04, 0.02). PLS-DA analysis showed that the individuals from each group were irregularly distributed according to their clade. Lactobacillus, Bifidobacterium and Ureaplasma were the dominant genera in all groups. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSts) analysis identified 31 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs associated with the bacterial communities from the four groups, including membrane transport, folding, sorting and degradation, xenobiotics biodegradation and metabolism, and nucleotide metabolism. We further determined relationships between pregnancy outcomes (Apgar scores) and certain bacterial species. A significant positive correlation was found between Apgar scores and Actinomyces neuii and Anoxybacillus flavithermus in the vagina and cervical canal of pregnant women with cervical incompetence while Bacteroides plebeius, Bifidobacterium pseudopodium and Staphylococcus petrasii in the cervical canal displayed negative correlations with Apgar scores. Moreover, Clostridium fimetarium, Methanobacterium congolense, Pseudomonas chlororaphis, and Psychrobacter nivimaris in the vagina were negatively correlated with Apgar scores. These bacteria may serve as potential biomarkers, however, additional research is warranted to verify their role in clinical outcomes.
Evaluation of the kitchen microbiome and food safety behaviors of predominantly low-income families
Authors: Carstens Christina K. , Salazar Joelle K. , Sharma Shreela V. , Chan Wenyaw , Darkoh Charles
Published: September 2022

Bacterial pathogens in the domestic environment present a risk to residents, particularly among susceptible populations. However, the impact of consumer demographic characteristics and food handling methods on kitchen microbiomes is not fully understood. The domestic kitchen bacterial communities of ten predominantly low-income families in Houston, TX, were assessed in conjunction with a cross-sectional food safety survey to evaluate differences in household and surface-specific microbiomes and bacterial foodborne pathogen presence. Three kitchen surfaces within each household, including the sink drain, the refrigerator handle, and the counter, were environmentally sampled and metataxonomically evaluated via targeted 16S rRNA sequencing. Disposable dish sponges were also acquired and examined. Results indicated that alpha diversity did not vary by the households, sampling locations, or demographic characteristics evaluated. Significant differences in beta diversity were observed among the bacterial communities of five pairs of households and between refrigerator handle and disposable dish sponge microbiomes. A total of 89 unique bacterial foodborne pathogens were identified across surface types. Each household contained at least one contaminated surface, and the most common bacterial foodborne pathogens identified were Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae. All parents reported washing their hands before meal preparation, washing fresh fruits and vegetables, and washing cutting boards with soap after use to prepare raw animal proteins. Gaps in food safety behaviors identified included a lack of serious concern for food contamination with germs and inappropriate handwashing, food handling, and cleaning behaviors. The number of unique bacterial foodborne pathogens identified within households was significantly higher among households whose respondent parent reported that they did not consider food contamination with germs to be a serious food safety problem (median: 41.0 species) compared to households whose respondent parent did consider food contamination to be a serious food safety problem (median: 3.0 species; p value = 0.0218). These results demonstrate that domestic kitchen taxonomic abundance profiles vary according to household and surface type. Data suggest that low-income consumers may be at risk of foodborne pathogen exposure from contaminated home kitchen surfaces, and that food safety attitudes may directly contribute to this hazard.
A new rapid and sensitive method for detecting chicken infectious anemia virus
Authors: Wu Xiuhong , Kong Jie , Yao Ziqi , Sun Hejing , Liu Yuanjia , Wu Zhiqiang , Liu Jiajia , Zhang Hao , Huang Haohua , Wang Jin , Chen Mengjun , Zeng Yichen , Huang Yinpeng , Chen Feng , Xie Qingmei , Zhang Xinheng
Published: September 2022

Since the chicken infectious anemia virus (CIAV) was discovered in 1979, which has been reported as an economically significant and immunosuppressive poultry disease in the world. A novel clinical detection method for the prevention and control of CIAV in the poultry sector is urgently needed. Here, we established a real-time recombinase-aided amplification assay (RAA) for CIAV on-site with a rapid, highly sensitive, strongly specific, low-cost, and simple operational molecular diagnosis detection method. The primers and probe were developed using the CIAV VP2 gene sequence, which has a 117-bp specific band. This assay, which could be carried out at 41°C and completed in 30 min without cross-reactivity with other viruses, had the lowest detection limit of 10 copies of CIAV DNA molecules per reaction. Furthermore, the kappa value of this assay was 0.947, the sensitivity was 93.33%, and the specificity was 100% when compared to the real-time quantitative polymerase chain reaction assay (real-time qPCR). These results indicate that using a real-time RAA assay to detect CIAV on-site could be beneficial. In the future, the real-time RAA test may be a regular assay for the prevention and control of CIAV, as well as help the reduction of economic losses in the poultry business.
Role of TM3 in claudin-15 strand flexibility: A molecular dynamics study
Authors: Fuladi Shadi , McGuinness Sarah , Khalili-Araghi Fatemeh
Published: September 2022

Claudins are cell-cell adhesion proteins within tight junctions that connect epithelial cells together. Claudins polymerize into a network of strand-like structures within the membrane of adjoining cells and create ion channels that control paracellular permeability to water and small molecules. Tight junction morphology and barrier function is tissue specific and regulated by claudin subtypes. Here, we present a molecular dynamics study of claudin-15 strands within lipid membranes and the role of a single-point mutation (A134P) on the third transmembrane helix (TM3) of claudin-15 in determining the morphology of the strand. Our results indicate that the A134P mutation significantly affects the lateral flexibility of the strands, increasing the persistence length of claudin-15 strands by a factor of three. Analyses of claudin-claudin contact in our μsecond-long trajectories show that the mutation does not alter the intermolecular contacts (interfaces) between claudins. However, the dynamics and frequency of interfacial contacts are significantly affected. The A134P mutation introduces a kink in TM3 of claudin-15 similar to the one observed in claudin-3 crystal structure. The kink on TM3 skews the rotational flexibility of the claudins in the strands and limits their fluctuation in one direction. This asymmetric movement in the context of the double rows reduces the lateral flexibility of the strand and leads to higher persistence lengths of the mutant.
Astragaloside IV supplementation attenuates cognitive impairment by inhibiting neuroinflammation and oxidative stress in type 2 diabetic mice
Authors: Zhang Yaxuan , Yuan Yuan , Zhang Jiawei , Zhao Yao , Zhang Yueqi , Fu Jianliang
Published: September 2022

Although diabetic cognitive impairment is one of the most common complications of type 2 diabetes mellitus (T2DM), optimized therapeutic strategies are not available yet. Astragalosides IV (AS-IV) is a traditional Chinese medicine possessing diverse pharmacological properties including anti-inflammatory and antioxidant effects. However, the effects of AS-IV on diabetes-related cognitive impairment and its precise mechanisms remain largely unknown. T2DM mice, induced by a high-fat diet (HFD) and an intraperitoneal injection of low-dose streptozotocin (STZ) were administrated with AS-IV every other day for eight consecutive weeks. Learning and memory abilities were assessed subsequently using the Ymaze test and the anxious behavior was evaluated using an open field test. Then, the morphology and number of neurons and microglia were observed by HE staining or immunohistochemistry. Oxidative stress biomarkers and pro-inflammatory cytokines were determined using relevant kits. In addition, the expression levels of Nrf2, Keap1, HO-1, and NQO1 were determined by Western blot analyses. The results indicated that AS-IV administration significantly improved neuronal damage and cognitive deficit in T2DM mice. Meanwhile, oxidative stress and neuroinflammation were also ameliorated in T2DM mice, which might be attributed to the regulation of Nrf2/Keap1/HO-1/NQO1 pathway in T2DM mice. Taken together, these data suggested that AS-IV ameliorates cognitive impairment in T2DM mice by attenuating oxidative stress and neuroinflammation, possibly through modulating the Nrf2/Keap1/HO1/NQO1 pathway.
Effects and mechanisms of mindfulness training and physical exercise on cognition, emotional wellbeing, and brain outcomes in chronic stroke patients: Study protocol of the MindFit project randomized controlled trial
Authors: Bermudo-Gallaguet Adrià , Ariza Mar , Dacosta-Aguayo Rosalia , Agudelo Daniela , Camins-Vila Neus , Boldó Maria , Carrera Òscar , Vidal Sandra , Ferrer-Uris Blai , Busquets Albert , Via Marc , Pera Guillem , Cáceres Cynthia , Gomis Meritxell , García-Molina Alberto , Tormos José María , Arrabé Ana , Diez Gustavo , Durà Mata Maria José , Torán-Monserrat Pere , Soriano-Raya Juan José , Domènech Sira , Perera-Lluna Alexandre , Erickson Kirk I. , Mataró Maria
Published: September 2022

Background

Post-stroke cognitive and emotional complications are frequent in the chronic stages of stroke and have important implications for the functionality and quality of life of those affected and their caregivers. Strategies such as mindfulness meditation, physical exercise (PE), or computerized cognitive training (CCT) may benefit stroke patients by impacting neuroplasticity and brain health.

Materials and methods

One hundred and forty-one chronic stroke patients are randomly allocated to receive mindfulness-based stress reduction + CCT (n = 47), multicomponent PE program + CCT (n = 47), or CCT alone (n = 47). Interventions consist of 12-week home-based programs five days per week. Before and after the interventions, we collect data from cognitive, psychological, and physical tests, blood and stool samples, and structural and functional brain scans.

Results

The effects of the interventions on cognitive and emotional outcomes will be described in intention-to-treat and per-protocol analyses. We will also explore potential mediators and moderators, such as genetic, molecular, brain, demographic, and clinical factors in our per-protocol sample.

Discussion

The MindFit Project is a randomized clinical trial that aims to assess the impact of mindfulness and PE combined with CCT on chronic stroke patients’ cognitive and emotional wellbeing. Furthermore, our design takes a multimodal biopsychosocial approach that will generate new knowledge at multiple levels of evidence, from molecular bases to behavioral changes.

Clinical trial registration

www.ClinicalTrials.gov, identifier NCT04759950.
Cannabinoids for behavioral symptoms in severe dementia: Safety and feasibility in a long-term pilot observational study in nineteen patients
Authors: Pautex Sophie , Bianchi Federica , Daali Youssef , Augsburger Marc , de Saussure Christian , Wampfler James , Curtin François , Desmeules Jules , Broers Barbara
Published: September 2022

Context

The management of behavioral symptoms and rigidity in patients with dementia constitutes a significant challenge. Short-term studies suggest an interest in the use of medical cannabis, but long-term data are lacking.

Objectives

The objective of this study was to investigate the feasibility and long-term safety of administering tetrahydrocannabinol/cannabidiol (THC/CBD) treatment as an additional drug to a poly medicated population with severe dementia, evaluate clinical improvements, and collect information on the pharmacokinetics of cannabinoids and possible drug–drug interactions.

Methods

A prospective observational study of patients with severe dementia living in a long-term care home to whom the physicians had prescribed a medical cannabis treatment. Data were collected over 2 years. We assessed the changes in medical cannabis dosages, safety parameters, variations in neuropsychiatric problems, agitation, rigidity, the most invalidating daily activity, and disabling behavior trouble scores. We evaluated the pharmacokinetics of cannabinoids by measuring plasma levels and analyzing the enzymatic activity.

Results

We assessed 19 patients (81.4 years—17 women and two men) receiving an average of 12.4 mg THC/24.8 mg CBD per day for up to 13 months, with no reported problems related to the treatment and limited adverse drug reactions. Clinical scores showed a marked improvement that was stable over time, deprescription of other medications, and care facilitated. The pharmacokinetic evaluation showed an expected slight reduction in the enzymatic activity of CYP1A2 and CYP2C19.

Conclusion

A long-term THC/CBD (1:2) medication can be administered safely and with overall positive clinical improvement to poly medicated older adults with severe dementia and associated problems. The results must be confirmed in a randomized trial.
Mediating roles of leukoaraiosis and infarcts in the effects of unilateral carotid artery stenosis on cognition
Authors: Huang Kuo-Lun , Chang Ting-Yu , Wu Yi-Ming , Chang Yeu-Jhy , Wu Hsiu-Chuan , Liu Chi-Hung , Lee Tsong-Hai , Ho Meng-Yang
Published: September 2022

Background and objectives

Leukoaraiosis and infarcts are common in patients with carotid artery stenosis (CAS), and CAS severity, leukoaraiosis and infarcts all have been implicated in cognitive impairments. CAS severity was not only hypothesized to directly impede specific cognitive domains, but also transmit its effects indirectly to cognitive function through ipsilateral infarcts as well as periventricular leukoaraiosis (PVL) and deep white matter leukoaraiosis (DWML). We aimed to delineate the contributions of leukoaraiosis, infarcts and CAS to different specific cognitive domains.

Materials and methods

One hundred and sixty one participants with unilateral CAS (>50%) on the left (n = 85) or right (n = 76) side and 65 volunteers without significant CAS (<50%) were recruited. The PVL, DWML, and infarct severity were visually rated on MRI. A comprehensive cognitive battery was administered and standardized based on age norms. Correlation and mediation analyses were adopted to examine the direct and indirect influence of CAS, leukoaraiosis, and infarct on specific cognitive domains with adjustment for education, hypertension, diabetes mellitus, and hyperlipidemia.

Results

Carotid artery stenosis severity was associated with ipsilateral leukoaraiosis and infarct. Left CAS had direct effects on most cognitive domains, except for visual memory and constructional ability, and transmitted its indirect effects on all cognitive domains through ipsilateral PVL, and on constructional ability and psychomotor through infarcts. Right CAS only had negative direct effects on visual memory, psychomotor, design fluency and color processing speed, and transmitted its indirect effects on visual memory, word and color processing speed through ipsilateral infarcts. The trends of direct and indirect cognitive effects remained similar after covariate adjustment.

Conclusion

Left and right CAS would predominantly lead to verbal and non-verbal cognitive impairment respectively, and such effects could be mediated through CAS-related leukoaraiosis and infarct. Given that cognition is subject to heterogeneous pathologies, the exact relationships between markers of large and small vessel diseases and their composite prognostic effects on cognition requires further investigation.
A novel predictive strategy for the incidence of postoperative neurocognitive dysfunction in elderly patients with mild cognitive impairment
Authors: Liang Yueying , Xin Xi , Wang Hongyan , Hua Wei , Wu Yi , Wang Xinyi , Li Ping , Zhou Tong , Wang Haiyun
Published: September 2022

Objective:Preoperative levels of cognition-related biomarkers and intraoperative cerebral ischemia and hypoxia might cause postoperative neurocognitive dysfunction (PND). The aim of this study was to evaluate the predictive ability of preoperative plasma biomarkers along with cerebral oxygen saturation (SctO2) for the incidence of PND in elderly patients with mild cognitive impairment (MCI).

Methods:A total of 210 patients aged 65–80 years undergoing spinal surgery were randomly assigned to three groups (n= 70 each): propofol, sevoflurane, and propofol/sevoflurane as anesthesia maintenance protocols. Propofol was administrated target-controlled infusion of 4 μg/ml (group P), the minimum alveolar concentration (MAC) of inhalation anesthetic sevoflurane was 1.3 (group S), and propofol was injected with a target-controlled plasma concentration of 1.2 μg/ml, accompanied by sevoflurane inhalation 0.7 MAC (group PS). Cognitive function was evaluated 1 day preoperatively and on the 7th day postoperatively. Preoperative levels of amyloidβ-40 (Aβ-40), Aβ-42, total tau protein (T-tau), phosphorylated tau protein (P-tau), and triggering receptors on myeloid cells-2 (TREM2) were investigated. SctO2was monitored intraoperatively.

Results:Aβ-42 had the strongest significant correlation with preoperative MoCA score. The value of Aβ-42 associated with a high risk of PND was 28.34 pg/ml, and the area under the curve (AUC) was predicted to be 0.711. When the preoperative level of Aβ-42 was 28.34 pg/ml, SctO2max% was 9.92%. The AUC was predicted to be 0.872, and the sensitivity and specificity were 0.833 and 0.841, respectively.

Conclusion:Under the conditions of preoperative Aβ-42 less than 28.34 pg/ml, the intraoperative fluctuation range of cerebral oxygen saturation should be maintained within 9.92% to reduce the occurrence of PND in geriatric patients with MCI.
Zinc enhances autophagic flux and lysosomal function through transcription factor EB activation and V-ATPase assembly
Authors: Kim Ki-Ryeong , Park Sang Eun , Hong Ji-Ye , Koh Jae-Young , Cho Dong-Hyung , Hwang Jung Jin , Kim Yang-Hee
Published: September 2022

The stimulation of autophagy or lysosomes has been considered therapeutic for neurodegenerative disorders because the accumulation of misfolded proteins is commonly observed in the brains of individuals with these diseases. Although zinc is known to play critical roles in the functions of lysosomes and autophagy, the mechanism behind this regulatory relationship remains unclear. Therefore, in this study, we examined which mechanism is involved in zinc-mediated activation of autophagy and lysosome. Exposure to zinc at a sub-lethal concentration activated autophagy in a concentration-dependent manner in mRFP-GFP-LC3-expressing H4 glioma cells. Zinc also rescued the blocking of autophagic flux arrested by pharmaceutical de-acidification. Co-treatment with zinc attenuated the chloroquine (CQ)-induced increase in the number and size of mRFP-GFP-LC3 puncta in H4 cells and accumulation of p62 by CQ or ammonium chloride in both H4 and mouse cerebrocortical cultures. Zinc rapidly induced the expression of cathepsin B (CTSB) and cathepsin D (CTSD), representative lysosomal proteases in neurons, which appeared likely to be mediated by transcription factor EB (TFEB). We observed the translocation of TFEB from neurite to nucleus and the dephosphorylation of TFEB by zinc. The addition of cycloheximide, a chemical inhibitor of protein synthesis, inhibited the activity of CTSB and CTSD at 8 h after zinc exposure but not at 1 h, indicating that only late lysosomal activation was dependent on the synthesis of CTSB and CTSD proteins. At the very early time point, the activation of cathepsins was mediated by an increased assembly of V-ATPase on lysosomes and resultant lysosomal acidification. Finally, considering that P301L mutation in tau protein causes frontotemporal dementia through aggressive tau accumulation, we investigated whether zinc reduces the accumulation of protein aggregates in SK-N-BE(2)-C neuroblastoma cells expressing wild-type tau or mutant P301L-tau. Zinc markedly attenuated the levels of phosphorylated tau and total tau as well as p62 in both wild-type and mutant tau-overexpressing cells. We also observed that zinc was more effective than rapamycin at inducing TFEB-dependent CTSB and CTSD expression and V-ATPase-dependent lysosomal acidification and CTSB/CTSD activation. These results suggest that the regulation of zinc homeostasis could be a new approach for developing treatments for neurodegenerative diseases, including Alzheimer’s and Parkinson’s.
Drug-related immune-mediated myelopathies
Authors: Gritsch David , Valencia-Sanchez Cristina
Published: September 2022

Iatrogenic immune-mediated inflammatory disorders of the spinal cord are an uncommon but potentially severe complication of drug therapy for several human diseases. Particularly the introduction of novel biological agents in the treatment of systemic inflammatory disorders and cancer immunotherapy have led to a significant increase in immune-related adverse events of the central nervous system (CNS). The use of Tumor necrosis factor alpha (TNF-alpha) inhibitors in rheumatic and inflammatory bowel diseases has been associated with demyelinating and other inflammatory CNS conditions, including myelitis. The introduction of immune checkpoint inhibitors in the treatment of several human malignancies has led to an increase in drug-induced immune-related adverse events including in the CNS. Other drugs that have been associated with immune-mediated myelitis include tyrosine-kinase inhibitors and chimeric antigen receptor (CAR) T Cell therapy. A high degree of suspicion is necessary when diagnosing these conditions, as early diagnosis and treatment is crucial in preventing further neurological damage and disability. The treatment of drug-induced inflammatory myelitis typically involves administration of high-dose intravenous corticosteroids, however additional immunosuppressive agents may be required in severe or refractory cases. While most cases are monophasic and remit following discontinuation of the offending agent, chronic immunosuppressive therapy may be indicated in cases with a progressive or relapsing disease course or when a diagnosis of a specific underlying neuro-inflammatory disorder is made. Outcomes are generally favorable, however depend on the specific therapeutic agent used, the clinical presentation and patient factors. In this review we aim to describe the clinical characteristics, imaging findings and management for the most common forms of iatrogenic immune-mediated myelopathies.
Distinct limbic connectivity in left and right benign mesial temporal lobe epilepsy: Evidence from a resting state functional MRI study
Authors: Pizzanelli Chiara , Pesaresi Ilaria , Milano Chiara , Cecchi Paolo , Fontanelli Lorenzo , Giannoni Sara , Giorgi Filippo Sean , Cosottini Mirco , Bonanni Enrica
Published: September 2022

Background

Functional connectivity (FC) studies showed that pharmaco-resistant mesial temporal lobe epilepsy (MTLE) affects not only the limbic system, but also several extra-limbic regions, including areas belonging to resting state networks. Less is known about FC in subjects with benign MTLE (i.e., sensitive to antiseizure medication, bMTLE).

Aim and methods

We evaluated FC of hippocampus and amygdala in subjects with bMTLE, distinguished based on the epileptic focus lateralization. We enrolled 19 patients (10 with left and 9 with right bMTLE) and 10 age-matched healthy subjects. Connectivity was investigated at rest by using a seed-based regression analyses approach with four regions of interest (left and right hippocampus, left and right amygdala). Patients were also tested with a neuropsychological battery and their scores were correlated with fMRI data.

Results and conclusions

Our study documented an asymmetrical disruption of FC in bMTLE, in relation to the side of the focus. Right subjects only exhibited limited altered connections, while left subjects—who performed worse in verbal memory tests—showed a wide bilateral hypoconnectivity of hippocampus and amygdala with areas belonging to language and memory network. The strength of FC between left limbic areas and language and memory network correlated with better performances in verbal memory tests. Moreover, we observed an increased FC with areas of default mode network, more pronounced in left subjects, a possible attempt to compensate cognitive deficit but without effectiveness.

We believe that these findings could help to better characterize bMTLE, in which a dysfunction of limbic connectivity is detectable despite well-controlled epilepsy.
Case report: A novel mosaic nonsense mutation of PCDH19 in a Chinese male with febrile epilepsy
Authors: Chen Guilan , Zhou Hang , Lu Yan , Wang You , Li Yingsi , Xue Jiaxin , Cheng Ken , Huang Ruibin , Han Jin
Published: September 2022

The clinical features of the PCDH19 gene mutation include febrile epilepsy ranging from mild to severe, with or without intellectual disability, cognitive impairment, and psych-behavioral disorders, but there has been little research on males with the mosaic mutation of PCDH19. This study reported a novel, de novo, and mosaic PCDH19 nonsense mutation (NM_001184880: c.840C > A, p. Tyr280*) from a Chinese male in early middle childhood by trio whole-exome sequence (Trio-WES) and confirmed by Sanger sequence. The proportion of the mosaic mutation (c.840C > A, p. Tyr280*) in PCDH19 was 27.9% in, buccal mucosal cells, 48.3% in exfoliated cells in the urine, and 50.6% in peripheral blood of proband. He had the first onset of seizures in toddlerhood with febrile epilepsy, mild impaired cognitive psychological, and behavioral abnormalities. The electroencephalography (EEG) exhibited sharp waves and sharp slow complex waves in the bilateral parietal, occipital, and posterior temporal regions during the interictal period. Pinpoint white matter lesions in the periventricular white matter and slightly bulging bilateral ventricles appeared on cranial magnetic resonance imaging (MRI). With Depakine and Keppra he gained good control over his epilepsy. This study might expand the genotypes and broaden the spectrums.
Association of resting-state theta–gamma coupling with selective visual attention in children with tic disorders
Authors: Ahn Ji Seon , Jhung Kyungun , Oh Jooyoung , Heo Jaeseok , Kim Jae-Jin , Park Jin Young
Published: September 2022

A tic disorder (TD) is a neurodevelopmental disorder characterized by tics, which are repetitive movements and/or vocalizations that occur due to aberrant sensory gating. Its pathophysiology involves dysfunction in multiple parts of the cortico-striato-thalamo-cortical circuits. Spontaneous brain activity during the resting state can be used to evaluate the baseline brain state, and it is associated with various aspects of behavior and cognitive processes. Theta–gamma coupling (TGC) is an emerging technique for examining how neural networks process information through interactions. However, the resting-state TGC of patients with TD and its correlation with cognitive function have not yet been studied. We investigated the resting-state TGC of 13 patients with TD and compared it with that of 13 age-matched healthy children. The participants underwent resting-state electroencephalography with their eyes closed. At the global level, patients with TD showed a significantly lower resting-state TGC than healthy children. Resting-state TGC with the eyes closed was significantly negatively correlated with the attention quotient calculated for omission errors in a selective visual attention test. These findings indicate that the resting-state brain network, which is important for the attentional processing of visual information, is dysfunctional in patients with TD. Additionally, these findings support the view that TGC reflects information processing and signal interactions at the global level. Patients with TD may have difficulty gating irrelevant sensory information in the resting state while their eyes are closed.
Interpersonal sensorimotor communication shapes intrapersonal coordination in a musical ensemble
Authors: Laroche Julien , Tomassini Alice , Volpe Gualtiero , Camurri Antonio , Fadiga Luciano , D’Ausilio Alessandro
Published: September 2022

Social behaviors rely on the coordination of multiple effectors within one’s own body as well as between the interacting bodies. However, little is known about how coupling at the interpersonal level impacts coordination among body parts at the intrapersonal level, especially in ecological, complex, situations. Here, we perturbed interpersonal sensorimotor communication in violin players of an orchestra and investigated how this impacted musicians’ intrapersonal movements coordination. More precisely, first section violinists were asked to turn their back to the conductor and to face the second section of violinists, who still faced the conductor. Motion capture of head and bow kinematics showed that altering the usual interpersonal coupling scheme increased intrapersonal coordination. Our perturbation also induced smaller yet more complex head movements, which spanned multiple, faster timescales that closely matched the metrical levels of the musical score. Importantly, perturbation differentially increased intrapersonal coordination across these timescales. We interpret this behavioral shift as a sensorimotor strategy that exploits periodical movements to effectively tune sensory processing in time and allows coping with the disruption in the interpersonal coupling scheme. As such, head movements, which are usually deemed to fulfill communicative functions, may possibly be adapted to help regulate own performance in time.