bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-transcriptional regulatory feedback encodes JAK-STAT signal memory of interferon stimulation
Authors: Kalliara Eirini , Kardynska Malgorzata , Bagnall James , Spiller David G. , Müller Werner , Ruckerl Dominik , Śmieja Jarosław , Biswas Subhra K. , Paszek Pawel
Published: September 2022

Immune cells fine tune their responses to infection and inflammatory cues. Here, using live-cell confocal microscopy and mathematical modelling, we investigate interferon-induced JAK-STAT signalling in innate immune macrophages. We demonstrate that transient exposure to IFN-γ stimulation induces a long-term desensitisation of STAT1 signalling and gene expression responses, revealing a dose- and time-dependent regulatory feedback that controls JAK-STAT responses upon re-exposure to stimulus. We show that IFN-α/β1 elicit different level of desensitisation from IFN-γ, where cells refractory to IFN-α/β1 are sensitive to IFN-γ, but notvice versa. We experimentally demonstrate that the underlying feedback mechanism involves regulation of STAT1 phosphorylation but is independent of new mRNA synthesis and cognate receptor expression. A new feedback model of the protein tyrosine phosphatase activity recapitulates experimental data and demonstrates JAK-STAT network’s ability to decode relative changes of dose, timing, and type of temporal interferon stimulation. These findings reveal that STAT desensitisation renders cells with signalling memory of type I and II interferon stimulation, which in the future may improve administration of interferon therapy.
Systematic pattern analyses of Vδ2+ TCRs reveal that shared “public” Vδ2+ γδ T cell clones are a consequence of rearrangement bias and a higher expansion status
Authors: Deng Lihua , Harms Anna , Ravens Sarina , Prinz Immo , Tan Likai
Published: September 2022

Background

Vγ9Vδ2+T cells are a major innate T cell subset in human peripheral blood. Their Vδ2+VDJ-rearrangements are short and simple in the fetal thymus and gradually increase in diversity and CDR3 length along with development. So-called “public” versions of Vδ2+TCRs are shared among individuals of all ages. However, it is unclear whether such frequently occurring “public” Vγ9Vδ2+T cell clones are derived from the fetal thymus and whether they are fitter to proliferate and persist than infrequent “private” clones.

Methods

Shared “public” Vδ2+TCRs were identified from Vδ2+TCR-repertoires collected from 89 individuals, including newborns (cord blood), infants, and adults (peripheral blood). Distance matrices of Vδ2+CDR3 were generated by TCRdist3 and then embedded into a UMAP for visualizing the heterogeneity of Vδ2+TCRs.

Results

Vδ2+CDR3 distance matrix embedded by UMAP revealed that the heterogeneity of Vδ2+TCRs is primarily determined by the J-usage and CDR3aa length, while age or publicity-specific motifs were not found. The most prevalent public Vδ2+TCRs showed germline-like rearrangement with low N-insertions. Age-related features were also identified. Public Vδ2+TRDJ1TCRs from cord blood showed higher N-insertions and longer CDR3 lengths. Synonymous codons resulting from VDJ rearrangement also contribute to the generation of public Vδ2+TCRs. Each public TCR was always produced by multiple different transcripts, even with different D gene usage, and the publicity of Vδ2+TCRs was positively associated with expansion status.

Conclusion

To conclude, the heterogeneity of Vδ2+TCRs is mainly determined byTRDJ-usage and the length of CDR3aa sequences. Public Vδ2+TCRs result from germline-like rearrangement and synonymous codons, associated with a higher expansion status.
COVID-19 vaccine hesitancy and associated factors among infertile couples undergoing assisted reproductive treatment
Authors: Wang Xinyan , Wang Huiyan , Du Aijun , Wang Junchao , Shi Jie , Zhang Yunshan , Zhang Yinfeng , Ma Junfang , Meng Wenjia , Lv Jiabei , Luo Haining
Published: September 2022

Although periconception vaccination is important to maternal and neonatal health, little is known about the COVID-19 vaccine hesitancy among infertile couples seeking fertility treatment. Thus, we conducted this survey among infertile patients in a reproductive medicine center, between September 2021 and December 2021, to estimate the prevalence of COVID-19 vaccine hesitancy and its influencing factors. Information was collected through face-to-face interviews among volunteers. Among the 987 included interviewees, 17.33% reported hesitancy in primary vaccination, 25.63% reported hesitancy in booster vaccination, and 32.32% delayed the primary vaccination. Hesitancy in primary vaccination was associated with unexplained infertility (OR: 1.77, 95% CI: 1.05-2.98), ongoing IVF treatment (OR: 2.17, 95% CI: 1.22-3.89), concerns for vaccine safety (OR: 4.13, 95% CI: 2.66-6.42), effectiveness (OR: 1.62, 95% CI: 1.15-2.28), and influence on pregnancy (OR: 2.80, 95% CI: 1.68-4.67). These factors were also associated with hesitancy in booster vaccination. Delay of the primary vaccination was inversely associated with a college or above degree (OR: 0.49, 95% CI: 0.27-0.87), previous history of influenza vaccination (OR: 0.67, 95% CI: 0.46-0.98), and was positively associated with concerns for the influence on pregnancy (OR: 7.78, 95% CI: 5.01-12.07). It is necessary to carry out targeted education program by health professionals to publicize the benefits of periconception vaccination, and to reduce the resistance to COVID-19 vaccine among infertile couples.
Exploring the risk factors for ischemic cerebrovascular disease in systemic lupus erythematosus: A single-center case-control study
Authors: Su Li , Qi Zhigang , Guan Shaochen , Wei Lian , Zhao Yi
Published: September 2022

Objectives

Ischemic cerebrovascular disease (ICVD) is one of the most common and severe complications in systemic lupus erythematosus (SLE). We aim to explore the risk factors for ICVD in SLE and to assess their associated clinical characteristics.

Methods

In this study, 44 lupus patients with ICVD (ICVD-SLE) and 80 age- and sex-matched lupus patients without ICVD (non-ICVD-SLE) who were hospitalized in our center between 2014 and 2021 were enrolled. A comprehensive set of clinical and socio-demographic data was recorded. In the ICVD-SLE group, the modified Rankin score (mRS) at 90 days after the occurrence of ICVD, the brain MRI, and arterial ultrasonography findings were collected. Group comparisons were made with continuous variables using an independent t-test or the Mann–Whitney test, and with categorical variables using the chi-square test or Fisher exact test. Multivariate logistic regression analysis was performed to identify the risk factors for ICVD in SLE. Patients with ICVD-SLE were divided into three subgroups according to the gradations of intracranial arterial stenosis (ICAS). The subgroup comparisons were performed by one-way ANOVA test or Kruskal–Wallis test.

Results

Of the 44 patients with ICVD, 45% had a large-vessel ischemic stroke, 50% had a symptomatic lacunar stroke, and 9% had a transient ischemic attack. 2 (4.5%) had both large-vessel ischemic stroke and symptomatic lacunar stroke. Multivariate logistic regression analysis showed that cutaneous vasculitis (OR=7.36, 95% CI=2.11–25.65), anticardiolipin antibody (aCL) (OR=4.38, 95% CI=1.435–13.350), and lupus anticoagulant (LA) (OR=7.543,95% CI=1.789–31.808) were the risk factors, and hydroxychloroquine (HCQ) therapy (OR=0.198, 95% CI=0.078–0.502) was the protective factor, after controlling for confounders. During the analysis of the subgroups, no significant difference was observed between the patients in the group without internal carotid arterial occlusion (ICAS) and those with severe ICAS except for diagnostic delay. However, patients in the moderate ICAS group were older when SLE occurred (P<0.01), had a longer diagnostic delay (P<0.01), a lower percentage of hypocomplementemia (P=0.05) and steroids and HCQ therapy (P=0.01, P=0.05, respectively), a trend toward lower mRS score, but a higher incidence of carotid atherosclerotic plaque (P<0.01), when compared with the other two subgroups.

Conclusion

Cutaneous vasculitis and antiphospholipid antibodies (aPLs) are associated with an increased risk of ICVD, while HCQ therapy may provide protection against ICVD in SLE. The ICVD in younger lupus patients is associated with complement-mediated inflammation and poorer outcome, and require immunosuppressive therapy, whereas the ICVD in elderly patients are characterized by moderate ICAS and carotid atherosclerotic plaques.
Predictive mutation signature of immunotherapy benefits in NSCLC based on machine learning algorithms
Authors: Liu Zhichao , Lin Guo , Yan Zeping , Li Linduo , Wu Xingchen , Shi Jingrong , He Jianxing , Zhao Lei , Liang Hengrui , Wang Wei
Published: September 2022

Background

Developing prediction tools for immunotherapy approaches is a clinically important and rapidly emerging field. The routinely used prediction biomarker is inaccurate and may not adequately utilize large amounts of medical data. Machine learning is a promising way to predict the benefit of immunotherapy from individual data by individuating the most important features from genomic data and clinical characteristics.

Methods

Machine learning was applied to identify a list of candidate genes that may predict immunotherapy benefits using data from the published cohort of 853 patients with NSCLC. We used XGBoost to capture nonlinear relations among many mutation genes and ICI benefits. The value of the derived machine learning-based mutation signature (ML-signature) on immunotherapy efficacy was evaluated and compared with the tumor mutational burden (TMB) and other clinical characteristics. The predictive power of ML-signature was also evaluated in independent cohorts of patients with NSCLC treated with ICI.

Results

We constructed the ML-signature based on 429 (training/validation = 8/2) patients who received immunotherapy and extracted 88 eligible predictive genes. Additionally, we conducted internal and external validation with the utility of the OAK+POPLAR dataset and independent cohorts, respectively. This ML-signature showed the enrichment in immune-related signaling pathways and compared to TMB, ML-signature was equipped with favorable predictive value and stratification.

Conclusion

Previous studies proposed no predictive difference between original TMB and modified TMB, and original TMB contains some genes with no predictive value. To demonstrate that fewer genetic tests are sufficient to predict immunotherapy efficacy, we used machine learning to screen out gene panels, which are used to calculate TMB. Therefore, we obtained the 88-gene panel, which showed the favorable prediction performance and stratification effect compared to the original TMB.
Volatiles from male honeydew excretions attract conspecific male spotted lanternflies, Lycorma delicatula (Hemiptera: Fulgoridae)
Authors: Faal Hajar , Meier Linnea R. , Canlas Isaiah J. , Murman Kelly , Wallace Matthew , Carrillo Daniel , Cooperband Miriam F.
Published: September 2022

The spotted lanternfly (SLF),Lycorma delicatula(Hemiptera: Fulgoridae), is a generalist phloem feeder that produces copious amounts of honeydew, which in turn coats the understory. These insects form large aggregations covering the trunks of some trees, while similar trees nearby mysteriously seem unattractive. We investigated whether volatiles from SLF honeydew are attractive to conspecifics by collecting honeydew from the field and testing it for SLF attraction in a two-choice olfactometer. We found that honeydew excreted by adult male SLF was significantly attractive to male SLF, but not female SLF. Although the honeydew excreted by adult female SLF did not significantly attract male or female SLF, both sexes showed a positive trend towards attraction in response to female honeydew in the olfactometer. Analysis of the headspace volatiles of honeydew was conducted, and numerous semiochemicals were identified. Five of which, 2-heptanone, 2-octanone, 2-nonanone, benzyl acetate, and 1-nonanol, were tested in two-choice behavioral assays against a blank control. Benzyl acetate and 2-octanone were attractive to both sexes, whereas 2-heptanone was only attractive to males, and 2-nonanone only to females. The remaining compound, 1-nonanol, repelled females, but not males. Although honeydew has been reported as a source of kairomones for some natural enemies, this may be the first report of sex-specific attractants for conspecific insects found in the honeydew volatiles of a planthopper.
Ocean acidification research in the Mediterranean Sea: Status, trends and next steps
Authors: Hassoun Abed El Rahman , Bantelman Ashley , Canu Donata , Comeau Steeve , Galdies Charles , Gattuso Jean-Pierre , Giani Michele , Grelaud Michaël , Hendriks Iris Eline , Ibello Valeria , Idrissi Mohammed , Krasakopoulou Evangelia , Shaltout Nayrah , Solidoro Cosimo , Swarzenski Peter W. , Ziveri Patrizia
Published: September 2022

Ocean acidification (OA) is a serious consequence of climate change with complex organism-to-ecosystem effects that have been observed through field observations but are mainly derived from experimental studies. Although OA trends and the resulting biological impacts are likely exacerbated in the semi-enclosed and highly populated Mediterranean Sea, some fundamental knowledge gaps still exist. These gaps are at tributed to both the uneven capacity for OA research that exists between Mediterranean countries, as well as to the subtle and long-term biological, physical and chemical interactions that define OA impacts. In this paper, we systematically analyzed the different aspects of OA research in the Mediterranean region based on two sources: the United Nation’s International Atomic Energy Agency’s (IAEA) Ocean Acidification International Coordination Center (OA-ICC) database, and an extensive survey. Our analysis shows that 1) there is an uneven geographic capacity in OA research, and illustrates that both the Algero-Provencal and Ionian sub-basins are currently the least studied Mediterranean areas, 2) the carbonate system is still poorly quantified in coastal zones, and long-term time-series are still sparse across the Mediterranean Sea, which is a challenge for studying its variability and assessing coastal OA trends, 3) the most studied groups of organisms are autotrophs (algae, phanerogams, phytoplankton), mollusks, and corals, while microbes, small mollusks (mainly pteropods), and sponges are among the least studied, 4) there is an overall paucity in socio-economic, paleontological, and modeling studies in the Mediterranean Sea, and 5) in spite of general resource availability and the agreement for improved and coordinated OA governance, there is a lack of consistent OA policies in the Mediterranean Sea. In addition to highlighting the current status, trends and gaps of OA research, this work also provides recommendations, based on both our literature assessment and a survey that targeted the Mediterranean OA scientific community. In light of the ongoing 2021-2030 United Nations Decade of Ocean Science for Sustainable Development, this work might provide a guideline to close gaps of knowledge in the Mediterranean OA research.

Systematic Review Registration

https://www.oceandecade.org/
The interaction between DOC released by cultured kelp (Saccharina japonica) and the bacterial community reveals the potential for increasing marine carbon sequestration by macroalgae culture
Authors: Zhang Mingliang , Qin Huawei , Wang Zhidong , Li Bin , Ma Yuanqing
Published: September 2022

Macroalgae culture as a marine carbon sequestration strategy has been recently proposed. To understand the potential for carbon sequestration by macroalgae culture, we studied the interaction of dissolved organic carbon (DOC) released by Saccharina japonica, an important cultured kelp species in China, and the bacterial community. We found that S. japonica effectively released DOC containing both labile and refractory components, and the DOC released by S. japonica into the water decreased average molecular weight (Masswa) by 18 Da, meaning it was rich in low molecular weight matter. Degradation of labile DOC components occurred during the initial 2 months of the experiment. The Masswa and molecular diversity of the DOC was increased in turn by bacterial degradation, and the variation in the DOC composition resulted in the succession of the bacterial community. During labile DOC degradation, anaerobic Gammaproteobacteria, Bacteroidia and Campylobacteria were the dominant microbial classes in the water, and aerobic Iodidimonadaceae became the dominant family during the final stage of the experiment. Finally, 5% of the DOC was transformed into refractory DOC. Although the sinking biomass was not involved in the study, the produced refractory DOC through the interaction between releasing DOC and bacterial degradation indicates a potential of carbon sequestration by macroalgae culture.
Microstructure-Sensitive Uncertainty Quantification for Crystal Plasticity Finite Element Constitutive Models Using Stochastic Collocation Methods
Authors: Tran Anh , Wildey Tim , Lim Hojun
Published: September 2022

Uncertainty quantification (UQ) plays a major role in verification and validation for computational engineering models and simulations, and establishes trust in the predictive capability of computational models. In the materials science and engineering context, where the process-structure-property-performance linkage is well known to be the only road mapping from manufacturing to engineering performance, numerous integrated computational materials engineering (ICME) models have been developed across a wide spectrum of length-scales and time-scales to relieve the burden of resource-intensive experiments. Within the structure-property linkage, crystal plasticity finite element method (CPFEM) models have been widely used since they are one of a few ICME toolboxes that allows numerical predictions, providing the bridge from microstructure to materials properties and performances. Several constitutive models have been proposed in the last few decades to capture the mechanics and plasticity behavior of materials. While some UQ studies have been performed, the robustness and uncertainty of these constitutive models have not been rigorously established. In this work, we apply a stochastic collocation (SC) method, which is mathematically rigorous and has been widely used in the field of UQ, to quantify the uncertainty of three most commonly used constitutive models in CPFEM, namely phenomenological models (with and without twinning), and dislocation-density-based constitutive models, for three different types of crystal structures, namely face-centered cubic (fcc) copper (Cu), body-centered cubic (bcc) tungsten (W), and hexagonal close packing (hcp) magnesium (Mg). Our numerical results not only quantify the uncertainty of these constitutive models in stress-strain curve, but also analyze the global sensitivity of the underlying constitutive parameters with respect to the initial yield behavior, which may be helpful for robust constitutive model calibration works in the future.
Factors Affecting Selection of a Dialysis Modality in Elderly Patients With Chronic Kidney Disease: A Prospective Cohort Study in Korea
Authors: Cho Jang-Hee , Lim Jeong-Hoon , Park Yeongwoo , Jeon Yena , Kim Yon Su , Kang Shin-Wook , Yang Chul Woo , Kim Nam-Ho , Jung Hee-Yeon , Choi Ji-Young , Park Sun-Hee , Kim Chan-Duck , Kim Yong-Lim
Published: September 2022

Background

We investigated factors associated with the selection of a dialysis modality for elderly patients compared to younger patients.

Methods

This study included 2,514 incident dialysis patients from a Korean multicenter prospective cohort. Multivariate logistic regression analyses were performed with demographic, socioeconomic, and clinical data to analyze factors associated with the chosen dialysis modality. Differences in these factors were compared between the elderly (≥65 years) and younger (<65 years) patients.

Results

Of the enrolled patients, 1,746 (69.5%) and 768 (30.6%) selected hemodialysis (HD) and peritoneal dialysis (PD), respectively. The percentage of PD was higher in younger patients than in elderly patients (37.1 vs. 16.9%, p < 0.001). Multivariate analysis showed that planned dialysis (p < 0.001), employment status (p < 0.001), and independent economic status (p = 0.048) were independent factors for selecting PD, whereas peripheral vascular disease (p = 0.038) and tumor (p = 0.010) were factors for selecting HD in the younger group. In the elderly group, planned dialysis (p < 0.001) and congestive heart failure (CHF; p = 0.002) were associated with choosing PD; however, tumor (p = 0.006) was associated with choosing HD. A two-way ANOVA showed that planned dialysis and CHF showed a significant interaction effect with age on modality selection.

Conclusions

As the age of patients with chronic kidney disease increased, HD was more frequently selected compared to PD. Dialysis planning and CHF interacted with age in selecting dialysis modalities in elderly patients. Elderly patients were less affected by socioeconomic status than younger patients.
Rethinking informed consent in the time of COVID-19: An exploratory survey
Authors: De Sutter Evelien , Lalova-Spinks Teodora , Borry Pascal , Valcke Peggy , Kindt Els , Negrouk Anastassia , Verhenneman Griet , Derèze Jean-Jacques , Storme Ruth , Huys Isabelle
Published: September 2022

Background

Owing to the infectious nature of COVID-19, alternative solutions, such as electronic informed consent (eIC), needed to be implemented to inform research participants about study-related information and to obtain their consent. This study aimed to investigate stakeholders’ experiences with alternative consenting methods as well as their views on any regulatory or legal guidelines for eIC implementation in clinical research. Results may serve as the cornerstone to rethink the informed consent process in clinical research.

Materials and methods

This study consisted of an online survey among three stakeholder groups across European Union (EU) Member States and the United Kingdom. The stakeholder groups included (i) investigators, (ii) data protection officers (DPOs) or legal experts working in the pharmaceutical industry, academia, and academic biobanks, and (iii) ethics committee (EC) members. Data collection occurred between April and December 2021. The data collected were analyzed using descriptive and inferential statistics.

Results

The online survey was completed by 191 respondents, of whom 52% were investigators. Respondents were active in 24 out of the 27 EU Member States and the United Kingdom. The majority of each stakeholder group considered validated electronic methods moderately or extremely useful to re-consent previously enrolled research participants upon study amendments or to obtain consent from COVID-19 patients. Nevertheless, this exploratory survey identified that only 13% of DPOs/legal experts, 26% of investigators, and 41% of EC members had experience with eIC. In addition, results suggest that the legal acceptance of eIC across EU Member States and the United Kingdom is variable and that a definition of eIC, issued by national law or policy, is rarely available. The results also showed that the COVID-19 pandemic brought additional challenges to inform participants and to obtain their consent; for example, related to travel restrictions.

Conclusion

A number of alternative consenting methods were recommended, for example by the European Medicines Agency, to ensure clinical study continuation during the COVID-19 pandemic. Although stakeholders support the use of eIC in clinical research, it seems that the experience with eIC is low. To harmonize eIC practices as much as possible, further investments in multi-stakeholder, multi-national guidance are needed.
Ehlers-Danlos syndromes and their manifestations in the visual system
Authors: Asanad Samuel , Bayomi May , Brown Douglas , Buzzard Joshua , Lai Eric , Ling Carlthan , Miglani Trisha , Mohammed Taariq , Tsai Joby , Uddin Olivia , Singman Eric
Published: September 2022

Ehlers-Danlos syndrome (EDS) is a rare, genetically variable, heterogenous group of (currently recognized) thirteen connective tissue disorders characterized by skin hyperextensibility, tissue fragility, and generalized joint hypermobility. In addition to these commonly recognized phenotypes, recent studies have notably highlighted variable ophthalmic features in EDS. In this review, we comprehensively gather and discuss the ocular manifestations of EDS and its thirteen subtypes in the clinical setting.
Characterization and subcellular localization of Alongshan virus proteins
Authors: Zhao Yinghua , Wu Ping , Liu Li , Ma Baohua , Pan Mingming , Huang Yuan , Du Nianyan , Yu Hongyan , Sui Liyan , Wang Ze-Dong , Hou Zhijun , Liu Quan
Published: September 2022

Alongshan virus (ALSV) in the Jingmenvirus group within the family Flaviviridae is a newly discovered tick-borne virus associated with human disease, whose genome includes four segments and encodes four structural proteins (VP1a, VP1b, VP2, VP3, and VP4) and two non-structural proteins (NSP1 and NSP2). Here, we characterized the subcellular distribution and potential function of ALSV proteins in host cells. We found that viral proteins exhibited diverse subcellular distribution in multiple tissue-deriving cells and induced various morphological changes in the endoplasmic reticulum (ER), and NSP2, VP1b, VP2, and VP4 were all co-localized in the ER. The nuclear transfer and co-localization of VP4 and calnexin (a marker protein of ER), which were independent of their interaction, were unique to HepG2 cells. Expression of NSP1 could significantly reduce mitochondria quantity by inducing mitophagy. These findings would contribute to better understanding of the pathogenesis of emerging segmented flaviviruses.
Multi-dimensional investigation and distribution characteristics analysis of gut microbiota of different marine fish in Fujian Province of China
Authors: Sun Hang , Chen Fangyi , Hao Hua , Wang Ke-Jian
Published: September 2022

The gut microbiota plays an important role in animal health and behavior. In marine fish, the composition of the gut microbiota is affected by many complex factors, such as diet, species, and regional factors. Since more than one hundred fish species have been cultured in fish farms along with the 3,324 km coastline of Fujian Province in South China, we chose this region to study the gut microbiota composition of marine commercial fishes because sufficient different species, diets, and regional factors were observed. We investigated the distribution characteristics of the gut microbiota of seven cultured species (Epinephelus akaara, Epinephelus coioides, Epinephelus lanceolatus ♂ × Epinephelus fuscoguttatus ♀, Siganus fuscescens, Pagrus major, Lateolabrax japonicus, and Acanthopagrus schlegelii) living in the same aquatic region and one species (E. akaara) living separately in five regions separated by latitude. The impacts of diet, region, and species factors on fish gut microbiota were also evaluated. Diversity and multivariate analyses showed that the patterns of the microbiota were significantly different in different fish species within the same habitat and E. akaara with five latitude regions. Mantel analysis showed that AN, SiO32–, DO, and NO2– were the principal factors affecting the microbial community of E. akaara in the five habitats. Additionally, similar distribution characteristics occurred in different gut parts of different fishes, with an increasing trend of Proteobacteria and Vibrionaceae abundance and a decreasing trend of Firmicutes and Bacillaceae abundance from the foregut to the hindgut. Vibrionaceae was the most abundant family in the content. This study highlights that a persistent core microbiota was established in marine commercial fishes spanning multiple scales. The factors with the greatest effect on fish gut microbiota may be (i) host genetics and (ii) geographic factors rather than the microbiota in the diet and water environment. These core microbes regularly colonized from the foregut to the hindgut, which was driven by their underlying functions, and they were well adapted to the gut environment. Moreover, the microbiota in the content may have contributed more to the gut microbial communities than previously reported. This study could complement basic data on the composition of marine commercial fishes and facilitate relatively complete investigations, which would be beneficial for the healthy and sustainable development of aquaculture.
Genome collection of Shewanella spp. isolated from spoiled lamb
Authors: Palevich Nikola , Palevich Faith P. , Gardner Amanda , Brightwell Gale , Mills John
Published: September 2022

The diversity of the genus Shewanella and their roles across a variety of ecological niches is largely unknown highlighting the phylogenetic diversity of these bacteria. From a food safety perspective, Shewanella species have been recognized as causative spoilage agents of vacuum-packed meat products. However, the genetic basis and metabolic pathways for the spoilage mechanism are yet to be explored due to the unavailability of relevant Shewanella strains and genomic resources. In this study, whole-genome sequencing of 32 Shewanella strains isolated from vacuum-packaged refrigerated spoiled lamb was performed to examine their roles in meat spoilage. Phylogenomic reconstruction revealed their genomic diversity with 28 Shewanella spp. strains belonging to the same putative novel species, two Shewanella glacialipiscicola strains (SM77 and SM91), Shewanella xiamenensis NZRM825, and Shewanella putrefaciens DSM 50426 (ATCC 8072) isolated from butter. Genome-wide clustering of orthologous gene families revealed functional groupings within the major Shewanella cluster but also considerable plasticity across the different species. Pan-genome analysis revealed conserved occurrence of spoilage genes associated with sulfur and putrescine metabolism, while the complete set of trimethylamine metabolism genes was observed in only Shewanella sp. SM74, S. glacialipiscicola SM77 and SM91 strains. Through comparative genomics, some variations were also identified pertaining to genes associated with adaptation to environmental cues such as temperature, osmotic, salt, oxidative, antimicrobial peptide, and drug resistance stresses. Here we provide a reference collection of draft Shewanella genomes for subsequent species descriptions and future investigations into the molecular spoilage mechanisms for further applications in the meat industry.
Combining affinity purification and mass spectrometry to define the network of the nuclear proteins interacting with the N-terminal region of FMRP
Authors: Kieffer Félicie , Hilal Fahd , Gay Anne-Sophie , Debayle Delphine , Pronot Marie , Poupon Gwénola , Lacagne Iliona , Bardoni Barbara , Martin Stéphane , Gwizdek Carole
Published: September 2022

Fragile X-Syndrome (FXS) represents the most common inherited form of intellectual disability and the leading monogenic cause of Autism Spectrum Disorders. In most cases, this disease results from the absence of expression of the protein FMRP encoded by the FMR1 gene (Fragile X messenger ribonucleoprotein 1). FMRP is mainly defined as a cytoplasmic RNA-binding protein regulating the local translation of thousands of target mRNAs. Interestingly, FMRP is also able to shuttle between the nucleus and the cytoplasm. However, to date, its roles in the nucleus of mammalian neurons are just emerging. To broaden our insight into the contribution of nuclear FMRP in mammalian neuronal physiology, we identified here a nuclear interactome of the protein by combining subcellular fractionation of rat forebrains with pull‐ down affinity purification and mass spectrometry analysis. By this approach, we listed 55 candidate nuclear partners. This interactome includes known nuclear FMRP-binding proteins as Adar or Rbm14 as well as several novel candidates, notably Ddx41, Poldip3, or Hnrnpa3 that we further validated by target‐specific approaches. Through our approach, we identified factors involved in different steps of mRNA biogenesis, as transcription, splicing, editing or nuclear export, revealing a potential central regulatory function of FMRP in the biogenesis of its target mRNAs. Therefore, our work considerably enlarges the nuclear proteins interaction network of FMRP in mammalian neurons and lays the basis for exciting future mechanistic studies deepening the roles of nuclear FMRP in neuronal physiology and the etiology of the FXS.
Full cervical cord tractography: A new method for clinical use
Authors: Dauleac Corentin , Frindel Carole , Pélissou-Guyotat Isabelle , Nicolas Célia , Yeh Fang-Cheng , Fernandez-Miranda Juan , Cotton François , Jacquesson Timothée
Published: September 2022

Despite recent improvements in diffusion-weighted imaging, spinal cord tractography is not used in routine clinical practice because of difficulties in reconstructing tractograms, with a pertinent tri-dimensional-rendering, in a long post-processing time. We propose a new full tractography approach to the cervical spinal cord without extensive manual filtering or multiple regions of interest seeding that could help neurosurgeons manage various spinal cord disorders. Four healthy volunteers and two patients with either cervical intramedullary tumors or spinal cord injuries were included. Diffusion-weighted images of the cervical spinal cord were acquired using a Philips 3 Tesla machine, 32 diffusion directions, 1,000 s/mm2b-value, 2 × 2 × 2 mm voxel size, reduced field-of-view (ZOOM), with two opposing phase-encoding directions. Distortion corrections were then achieved using the FSL software package, and tracking of the full cervical spinal cord was performed using the DSI Studio software (quantitative anisotropy-based deterministic algorithm). A unique region of avoidance was used to exclude everything that is not of the nervous system. Fiber tracking parameters used adaptative fractional anisotropy from 0.015 to 0.045, fiber length from 10 to 1,000 mm, and angular threshold of 90°. In all participants, a full cervical cord tractography was performed from the medulla to the C7 spine level. On a ventral view, the junction between the medulla and spinal cord was identified with its pyramidal bulging, and by an invagination corresponding to the median ventral sulcus. On a dorsal view, the fourth ventricle—superior, middle, and inferior cerebellar peduncles—was seen, as well as its floor and the obex; and gracile and cuneate tracts were recognized on each side of the dorsal median sulcus. In the case of the intramedullary tumor or spinal cord injury, the spinal tracts were seen to be displaced, and this helped to adjust the neurosurgical strategy. This new full tractography approach simplifies the tractography pipeline and provides a reliable 3D-rendering of the spinal cord that could help to adjust the neurosurgical strategy.
A brainnetome atlas-based methamphetamine dependence identification using neighborhood component analysis and machine learning on functional MRI data
Authors: Zhou Yanan , Tang Jingsong , Sun Yunkai , Yang Winson Fu Zun , Ma Yuejiao , Wu Qiuxia , Chen Shubao , Wang Qianjin , Hao Yuzhu , Wang Yunfei , Li Manyun , Liu Tieqiao , Liao Yanhui
Published: September 2022

Addiction to methamphetamine (MA) is a major public health concern. Developing a predictive model that can classify and characterize the brain-based biomarkers predicting MA addicts may directly lead to improved treatment outcomes. In the current study, we applied the support vector machine (SVM)-based classification method to resting-state functional magnetic resonance imaging (rs-fMRI) data obtained from individuals with methamphetamine use disorder (MUD) and healthy controls (HCs) to identify brain-based features predictive of MUD. Brain connectivity analyses were conducted for 36 individuals with MUD as well as 37 HCs based on the brainnetome atlas, and the neighborhood component analysis was applied for feature selection. Eighteen most relevant features were screened out and fed into the SVM to classify the data. The classifier was able to differentiate individuals with MUD from HCs with a high prediction accuracy, sensitivity, specificity, and AUC of 88.00, 86.84, 89.19, and 0.94, respectively. The top six discriminative features associated with changes in the functional activity of key nodes in the default mode network (DMN), all the remaining discriminative features are related to the thalamic connections within the cortico-striato-thalamo-cortical (CSTC) loop. In addition, the functional connectivity (FC) between the bilateral inferior parietal lobule (IPL) and right cingulate gyrus (CG) was significantly correlated with the duration of methamphetamine use. The results of this study not only indicated that MUD-related FC alterations were predictive of group membership, but also suggested that machine learning techniques could be used for the identification of MUD-related imaging biomarkers.
Dynamic immune and exosome transcriptomic responses in patients undergoing psychostimulant methamphetamine withdrawal
Authors: Wu Hongjin , Zhang Zunyue , Ma Yuru , Chen Fengrong , Xiong Pu , Xie Zhenrong , Ding Guo , Yu Juehua , Wang Kunhua
Published: September 2022

Methamphetamine (METH) addiction and withdrawal cause serious harm to both the immune system and nervous system. However, the pathogenesis remains largely unknown. Herein, we investigated the peripheral cytokines and exosomal transcriptome regulatory networks in the patients with METH use disorders (MUDs) undergoing withdrawal. Twenty-seven cytokines were simultaneously assessed in 51 subjects, including 22 at the acute withdrawal (AW) stage and 29 at the protracted withdrawal (PW) stage, and 31 age and gender-matched healthy controls (HCs). Compared to the HCs, significantly decreased levels of interleukin (IL)-1β, IL-9, IL-15, Basic FGF, and MIP1a, increased levels of IL-1rα, IL-6, Eotaxin IP-10, VEGF, and RANTES were identified in AW. These disturbances were mostly or partly restored to the baseline in PW. However, the cytokines IL-6, IL-7, and IL-12p70 were consistently increased even after one year of withdrawal. Besides, a significant decrease in CD3+T and CD4+T cell numbers was observed in AW, and the diminishment was restored to baseline in PW. Comparatively, there were no statistically significant changes in CD8+T, NK, and B cells. Furthermore, the exosomal mRNAs and long non-coding RNAs (lncRNA) were profiled, and the lncRNA-miRNA-mRNA networks were constructed and associated with METH AW and PW stages. Notably, the chemokine signaling was remarkably upregulated during AW. By contrast, the differentially expressed mRNAs/lincRNAs were significantly enriched in neurodegeneration-related diseases. Taken together, a group of METH withdrawal-related cytokines and exosomal mRNA/lncRNA regulatory networks were obtained, which provides a useful experimental and theoretical basis for further understanding of the pathogenesis of the withdrawal symptoms in MUDs.
Diseased, differentiated and difficult: Strategies for improved engineering of in vitro neurological systems
Authors: Elder Nicholas , Fattahi Faranak , McDevitt Todd C. , Zholudeva Lyandysha V.
Published: September 2022

The rapidly growing field of cellular engineering is enabling scientists to more effectively create in vitro models of disease and develop specific cell types that can be used to repair damaged tissue. In particular, the engineering of neurons and other components of the nervous system is at the forefront of this field. The methods used to engineer neural cells can be largely divided into systems that undergo directed differentiation through exogenous stimulation (i.e., via small molecules, arguably following developmental pathways) and those that undergo induced differentiation via protein overexpression (i.e., genetically induced and activated; arguably bypassing developmental pathways). Here, we highlight the differences between directed differentiation and induced differentiation strategies, how they can complement one another to generate specific cell phenotypes, and impacts of each strategy on downstream applications. Continued research in this nascent field will lead to the development of improved models of neurological circuits and novel treatments for those living with neurological injury and disease.
NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain
Authors: Liu Ya-Jing , Li Yue-Ling , Fang Zhong-Han , Liao Hong-Lin , Zhang Yan-Yan , Lin Jiu , Liu Fei , Shen Jie-Fei
Published: September 2022

Peripheral and central sensitizations of the trigeminal nervous system are the main mechanisms to promote the development and maintenance of chronic orofacial pain characterized by allodynia, hyperalgesia, and ectopic pain after trigeminal nerve injury or inflammation. Although the pathomechanisms of chronic orofacial pain are complex and not well known, sufficient clinical and preclinical evidence supports the contribution of the N-methyl-D-aspartate receptors (NMDARs, a subclass of ionotropic glutamate receptors) to the trigeminal nociceptive signal processing pathway under various pathological conditions. NMDARs not only have been implicated as a potential mediator of pain-related neuroplasticity in the peripheral nervous system (PNS) but also mediate excitatory synaptic transmission and synaptic plasticity in the central nervous system (CNS). In this review, we focus on the pivotal roles and mechanisms of NMDARs in the trigeminal nervous system under orofacial neuropathic and inflammatory pain. In particular, we summarize the types, components, and distribution of NMDARs in the trigeminal nervous system. Besides, we discuss the regulatory roles of neuron-nonneuronal cell/neuron-neuron communication mediated by NMDARs in the peripheral mechanisms of chronic orofacial pain following neuropathic injury and inflammation. Furthermore, we review the functional roles and mechanisms of NMDARs in the ascending and descending circuits under orofacial neuropathic and inflammatory pain conditions, which contribute to the central sensitization. These findings are not only relevant to understanding the underlying mechanisms, but also shed new light on the targeted therapy of chronic orofacial pain.
Long-term predictivity of early neurological assessment and developmental trajectories in low-risk preterm infants
Authors: Dicanio Daniela , Spoto Giulia , Alibrandi Angela , Minutoli Roberta , Nicotera Antonio Gennaro , Di Rosa Gabriella
Published: September 2022

Prematurity represents 10.6% of all births, and although preterm infants usually show adequate neurodevelopmental outcomes, some may develop significant and long-lasting neurological sequelae. Many studies have analyzed predictive factors for developing severe neurodevelopmental impairments (cerebral palsy, other motor and socio-relational disorders such as autism). In this study, 148 preterm infants were enrolled to investigate the neurodevelopmental trajectories in a population of low-risk premature infants using standardized assessment methods. Significant correlations were found between the general movements, the Hammersmith Infant Neurological Examination, and the Griffiths Mental and Development Scales. Moreover, this study showed their validity and predictivity for adverse neurodevelopmental outcomes even in low-risk infants.
Are preoperative phase-contrast CSF flow parameters ideal for predicting the outcome of shunt surgery in patients with idiopathic normal pressure hydrocephalus?
Authors: He Wen-Jie , Zhang Xie-jun , Xu Qi-Zhong , Bai Run-tao , Chen Jia-kuan , Zhou Xi , Xia Jun
Published: September 2022

Purpose

Phase-contrast magnetic resonance (PC-MR) is widely used in patients with idiopathic normal pressure hydrocephalus (iNPH), but its role in predicting prognosis remains controversial. To evaluate the effectiveness of preoperative PC-MR CSF flow measurement in predicting the clinical response to shunt surgery in patients with iNPH.

Methods

Forty-six patients with definite iNPH were included between January 2018 and January 2022. PC-MR was used to evaluate CSF peak velocity (PV), average velocity, aqueductal stroke volume (ASV), net ASV, and net flow. The modified Rankin Scale (mRS), iNPH grading scale (iNPHGS), Mini-Mental State Examination (MMSE), and Timed 3-m Up and Go Test (TUG) were used for clinical assessment. The primary endpoint was the improvement in the mRS score 1 year after surgery, and the secondary endpoints were the iNPHGS, MMSE, and TUG scores at 1 year. Differences between shunt improvement and non-improvement groups, based on the clinical outcomes, were compared using the Mann-Whitney U-test, logistic regression models, and receiver operating characteristic curves. Correlations between CSF flow parameters and the baseline clinical outcomes were assessed using Spearman's correlation coefficient.

Results

No CSF parameters significantly differed between shunt improvement and non-improvement groups based on mRS and secondary outcomes. And all CSF parameters showed significant overlap in both shunt improvement and non-improvement groups based on mRS and secondary outcomes. Significant correlations between the mRS and iNPHGS scores, and PV, ASV, and net ASV were observed.

Conclusion

While some preoperative PC-MR CSF flow parameters reflected the symptom severity of iNPH to a certain extent, they alone might not be ideal markers of shunt responsiveness.
A rise in saliva and urine pH in children with SCN1A-related epilepsy: An exploratory prospective controlled study
Authors: Lu Qian , Wang Yang-Yang , Chen Hui-Min , Wang Qiu-Hong , Yang Xiao-Yan , Zou Li-Ping
Published: September 2022

Objective

SCN1A, encoding the alpha 1 subunit of the sodium channel, is associated with a range of related epilepsy. This study aims to assess saliva and urine pH in children with SCN1A-related epilepsy.

Methods

A prospective controlled observational study with a 1:1 ratio was conducted on seven patients with SCN1A-related epilepsy and seven healthy children of the same family, gender, and age but without a history of seizures. The pH of saliva and urine was measured by pH test paper. Parents of patients with epilepsy recorded seizures to compare the relationship between pH and seizures.

Results

The fourteen participants were all males, aged 1 to 14 years. Seven patients had different pathogenic SCN1A variants. The pH of saliva and urine was monitored for 21–95 days. The pH of saliva and urine was higher in patients with SCN1A-related epilepsy than in the healthy group. The urine pH in Dravet syndrome patients was high compared with other epilepsy patients. The urine pH in patients with seizures was higher than that in patients without seizures, which occurred during the study.

Conclusions

The pH of saliva and urine was chronically high in patients with SCN1A-related epilepsy, and urine pH was higher in patients with seizures and with Dravet syndrome.