Does host migration affect host-parasite interaction? Migrant birds harbor exclusive parasites but have similar roles in parasite-host networks.

Parasites comprise a substantial portion of global biodiversity and play critical roles in shaping ecosystems by modulating trophic networks and affecting their hosts' abundance and distribution. The dynamics of host migration introduce new complexity to these relationships. From the host perspective, migratory behavior can either act as a defense mechanism or augment exposure to a broader spectrum of pathogens. Conversely, for parasites, host migration represents a mechanism for their dispersion and an opportunity to infect new host species. This study investigates the complex interplay between migration and parasite-host interactions, focusing on the interaction between hosts and avian malaria and malaria-like parasites in the Brazilian Atlantic Rain Forest. We captured 1466 birds representing 70 different species, uncovering 322 infections with Plasmodium/Haemoproteus parasites. We observed variations in migration timing and fluctuations in host abundance across months. By comparing the observed patterns of interaction of migratory and non-migratory birds to patterns of interaction expected at random, we show that migration affects the roles hosts take in the parasite-host network. Interestingly, despite the fact migratory species hosted more exclusive and distinct parasites, migrants did not occupy central network positions, which are mostly occupied by resident birds. Overall, we highlight the role of resident birds as a key species within parasite-host communities and the high specialization among avian haemosporidians and their hosts.

A novel histone deacetylase inhibitor W2A-16 improves the barrier integrity in brain vascular endothelial cells.

The maturation of brain microvascular endothelial cells leads to the formation of a tightly sealed monolayer, known as the blood-brain barrier (BBB). The BBB damage is associated with the pathogenesis of age-related neurodegenerative diseases including vascular cognitive impairment and Alzheimer's disease. Growing knowledge in the field of epigenetics can enhance the understanding of molecular profile of the BBB and has great potential for the development of novel therapeutic strategies or targets to repair a disrupted BBB. Histone deacetylases (HDACs) inhibitors are epigenetic regulators that can induce acetylation of histones and induce open chromatin conformation, promoting gene expression by enhancing the binding of DNA with transcription factors. We investigated how HDAC inhibition influences the barrier integrity using immortalized human endothelial cells (HCMEC/D3) and the human induced pluripotent stem cell (iPSC)-derived brain vascular endothelial cells. The endothelial cells were treated with or without a novel compound named W2A-16. W2A-16 not only activates Wnt/ß-catenin signaling but also functions as a class I HDAC inhibitor. We demonstrated that the administration with W2A-16 sustained barrier properties of the monolayer of endothelial cells, as evidenced by increased trans-endothelial electrical resistance (TEER). The BBB-related genes and protein expression were also increased compared with non-treated controls. Analysis of transcript profiles through RNA-sequencing in hCMEC/D3 cells indicated that W2A-16 potentially enhances BBB integrity by influencing genes associated with the regulation of the extracellular microenvironment. These findings collectively propose that the HDAC inhibition by W2A-16 plays a facilitating role in the formation of the BBB. Pharmacological approaches to inhibit HDAC may be a potential therapeutic strategy to boost and/or restore BBB integrity.

The cross-sectional and longitudinal interconnectedness of physical, psychological and role functioning following physical trauma: A network analysis.

OBJECTIVE: Surviving physical trauma can have a large impact on one's daily life. Patients are at increased risk for poor physical health, psychological complaints, and problems in role functioning - which is often experienced simultaneously. The present study explores the interconnectedness of physical, psychological, and role functioning during the first two years post-injury, both cross-sectionally and longitudinally from a network perspective. METHODS: 3785 trauma patients (Mage = 64.2 years, SDage = 18.9 years, 50.5% female) completed questionnaires on physical, psychological, and role functioning across six measurement occasions during the first two years post-injury. The Injury Severity Score (ISS) was retrieved from the local trauma registry. Mixed graphical network models and cross-lagged network models were estimated to examine which items of recovery played a central role and were mostly related to other items in cross-sectional and longitudinal networks respectively. RESULTS: The cross-sectional networks showed especially strong interconnections between impairments of physical and role functioning and also within post-traumatic stress symptoms. The longitudinal networks extended these results by showing that pain, impaired mobility, limitations in self-care, anxiety/depressive symptoms, and several post-traumatic stress symptoms were strong predictors for impairments in functioning at later stages of recovery. CONCLUSION: Our findings showed that impairments in physical, psychological, and role functioning experienced by trauma patients are largely intertwined across the two years following injury. Monitoring physical impairments and psychological complaints early in recovery might help to more promptly provide the best fitting aftercare for trauma patients, which can improve recovery on the long-term.

Transcriptional network analysis of peripheral blood leukocyte subsets in multiple sclerosis identifies a pathogenic role for a cytotoxicity-associated gene network in myeloid cells.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system affecting predominantly adults. It is a complex disease associated with both environmental and genetic risk factors. Although over 230 risk single-nucleotide polymorphisms have been associated with MS, all are common human variants. The mechanisms by which they increase the risk of MS, however, remain elusive. We hypothesized that a complex genetic phenotype such as MS could be driven by coordinated expression of genes controlled by transcriptional regulatory networks. We, therefore, constructed a gene coexpression network from microarray expression analyses of five purified peripheral blood leukocyte subsets of 76 patients with relapsing remitting MS and 104 healthy controls. These analyses identified a major network (or module) of expressed genes associated with MS that play key roles in cell-mediated cytotoxicity which was downregulated in monocytes of patients with MS. Manipulation of the module gene expression was achieved in vitro through small interfering RNA gene knockdown of identified drivers. In a mouse model, network gene knockdown modulated the autoimmune inflammatory MS model disease-experimental autoimmune encephalomyelitis. This research implicates a cytotoxicity-associated gene network in myeloid cells in the pathogenesis of MS.

The comorbidity mechanism of problematic internet use and depression among Chinese college students: A cross-lagged panel network analysis.

Problematic internet use (PIU) and depression usually co-occur and are common among college students. According to network theory, it may be attributed to the interplay of symptoms that connect these two mental health problems. However, most studies have failed to examine complex and subtle connections at the symptom level and have not clarified how PIU and depression symptoms are intercorrelated, which symptoms serve as the source of comorbidity (i.e., the central symptoms), and whether such a comorbidity mechanism would change with higher grades. To explore these questions, this study examined four contemporaneous networks and three cross-lagged panel networks, visualizing the symptoms as nodes and the connections between symptoms as edges. A total of 2,420 college students (Mage = 18.35, SD = 0.84; 67.98 % girls) completed four annual surveys. Overall, the results of contemporaneous networks and cross-lagged panel networks indicated that (a) PIU and depression symptoms are intercorrelated; (b) the core symptoms responsible for comorbidity mostly belonged to PIU, and (c) the comorbidity mechanism would change with time. These findings explain the dynamic relation between PIU and depression and identify possible primary symptoms that comorbidity programs can mitigate at different stages of the college years.

Associations Between Internet-Specific Parenting, General Parenting, and Adolescents' Online Behaviors: A Cross-Lagged Panel Network Analysis.

Parents play a crucial role in adolescents' Internet use. Both general parenting (i.e., autonomy-supportive and controlling parenting) and Internet-specific parenting (i.e., restrictive mediation, active mediation, and parental encouragement) are related to adolescents' online behaviors. However, existing studies have focused either on an Internet-specific parenting or general parenting strategy and have neglected their interaction, failing to capture the intricate nature of the parenting context of youth's online behaviors. Few studies have examined parental encouragement or acknowledged the bidirectional influence of parenting on adolescents' online behaviors. To address this gap, this study employed a cross-lagged panel network model to examine the associations among restrictive and active mediation, parental encouragement, and autonomy-supportive and controlling parenting, as well as the interplay of all five parenting strategies with adolescents' online behaviors. A total of 564 Chinese students (51.1% male; mean age = 14.54, SD = 0.7) completed the survey at two time points. The results indicate that in most cases, previous online behaviors are significant and strong predictors of subsequent parenting strategies and not vice versa, corroborating the child effect. The parent and reciprocal effects were observed in the problematic smartphone-use domain, suggesting that the effects may differ for distinct behavioral domains. The effects of parental mediation extend beyond parental encouragement, implying that risk-prevention-related parenting is an effective means of guiding adolescents' online behaviors. Autonomy-relevant general parenting is closely related to active mediation and parental encouragement, while restrictive general parenting is closely related to restrictive mediation, suggesting a consistency between Internet-specific and general parenting strategies.

Plant networks are more connected by invasive brome and native shrub facilitation in Central California drylands.

Dominant vegetation in many ecosystems is an integral component of structure and habitat. In many drylands, native shrubs function as foundation species that benefit other plants and animals. However, invasive exotic plant species can comprise a significant proportion of the vegetation. In Central California drylands, the facilitative shrub Ephedra californica and the invasive Bromus rubens are widely dispersed and common. Using comprehensive survey data structured by shrub and open gaps for the region, we compared network structure with and without this native shrub canopy and with and without the invasive brome. The presence of the invasive brome profoundly shifted the network measure of centrality in the microsites structured by a shrub canopy (centrality scores increased from 4.3 under shrubs without brome to 6.3, i.e. a relative increase of 42%). This strongly suggests that plant species such as brome can undermine the positive and stabilizing effects of native foundation plant species provided by shrubs in drylands by changing the frequency that the remaining species connect to one another. The net proportion of positive and negative associations was consistent across all microsites (approximately 50% with a total of 14% non-random co-occurrences on average) suggesting that these plant-plant networks are rewired but not more negative. Maintaining resilience in biodiversity thus needs to capitalize on protecting native shrubs whilst also controlling invasive grass species particularly when associated with shrubs.

Deletion of PTP4A3 phosphatase in high grade serous ovarian cancer cells decreases tumorigenicity and produces marked changes in intracellular signaling pathways and cytokine release.

The oncogenic protein tyrosine phosphatase PTP4A3 is frequently overexpressed in human ovarian cancers and is associated with poor patient prognosis. PTP4A3 is thought to regulate multiple oncogenic signaling pathways, including STAT3, SRC, and ERK. The objective of this study was to generate ovarian cancer cells with genetically depleted PTP4A3; to assess their tumorigenicity; to examine their cellular phenotype; and to uncover changes in their intracellular signaling pathways and cytokine release profiles. Genetic deletion of PTP4A3 using CRISPR/Cas9 enabled the generation of individual clones derived from single cells isolated from the polyclonal knockout population. We observed a >90% depletion of PTP4A3 protein levels by Western blotting in the clonal cell lines compared to the sham transfected wildtype population. The wildtype and polyclonal knockout cell lines shared similar monolayer growth rates, while the isolated clonal populations 2B4, 3C9, and 3C12 exhibited significantly lower monolayer growth characteristics consistent with their lower PTP4A3 levels. The clonal PTP4A3 knockout cell lines also had substantially lower in vitro colony formation efficiencies compared to the wildtype cells and were less tumorigenic in vivo The clonal knockout cells were markedly less responsive to IL-6-stimulated migration in a scratch wound assay compared to the wildtype cells. Antibody microarray assays documented differences in cytokine release and intracellular phosphorylation patterns in the PTP4A3 deleted clones. Bioinformatic network analyses indicated alterations in cellular signaling nodes. These biochemical changes could ultimately form the foundation for pharmacodynamic endpoints useful for emerging anti-PTP4A3 therapeutics. Significance Statement Clones of high grade serous ovarian cancer cells were isolated in which the oncogenic phosphatase PTP4A3 was deleted using CRISPR/Cas9 methodologies. The PTP4A3 null cells exhibited loss of in vitro proliferation, colony formation, and migration, and reduced in vivo tumorigenesis. Marked differences in intracellular protein phosphorylation and cytokine release were seen. The newly developed PTP4A3 knockout cells should provide useful tools to probe the role of PTP4A3 phosphatase in ovarian cancer cell survival, tumorigenicity and cell signaling.

Self-regulatory control processes in youths: A temporal network analysis approach.

Objective: This study aimed to better understand the temporal interrelationships among self-control, response inhibition, and anger (i.e., momentary state and rumination) on both the within- and between-person levels in male adolescents. Method: We applied temporal network analyses among 62 male adolescents with a wide range of behavioral difficulties. Self-control, momentary anger, and anger rumination were mapped by self-report measures, whereas we measured response inhibition through an ambulatory Go/No-go task (two measures a day-morning and afternoon-over a 9-day period). Results: Temporal network analysis, at the within-person level, revealed that morning measures of response inhibition, anger rumination, and self-control were related to the corresponding measure in the afternoon. More efficient response inhibition in the morning was associated with higher self-control in the afternoon. Higher anger rumination in the morning led to higher momentary anger in the afternoon. In a concurrent within-person network, higher momentary anger was reciprocally associated with lower self-control. At the between-person level, higher momentary anger was correlated to higher anger rumination, lower response inhibition, and lower self-control. Discussion: This study provides insight into the dynamic interactions among self-control, response inhibition, and anger (momentary state and rumination) in male adolescents, advancing the understanding of self-regulatory control functioning.

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

New insight into social relationships in dairy cows and how time of birth, parity, and relatedness affect spatial interactions later in life.

Social interactions between cows play a fundamental role in the daily activities of dairy cattle. Real-time location systems provide on a continuous and automated basis information about the position of individual cows inside barns, offering a valuable opportunity to monitor dyadic social contacts. Understanding dyadic social interactions could be applied to enhance the stability of the social structure promoting animal welfare and to model disease transmission in dairy cattle. This study aimed to identify the effect of different cow characteristics on the likelihood of the formation and persistence of social contacts in dairy cattle. The individual position of the lactating cows was automatically collected once per second for 2 wk, using an ultra-wideband system on a Swedish commercial farm consisting of almost 200 dairy cows inside a freestall barn. Social networks were constructed using the position data of 149 cows with available information on all characteristics during the study period. Social contacts were considered as a binary variable indicating whether a cow pair was within 2.5 m of each other for at least 10 min per day. The role of cow characteristics in social networks was studied by applying separable temporal exponential random graph models. Our results revealed that cows of the same parity interacted more consistently, as well as those born within 7 d of each other or closely related by pedigree. The repeatability of the topological parameters indicated a consistent short-term stability of the individual animal roles within the social network structure. Additional research is required to elucidate the underlying mechanisms governing the long-term evolution of social contacts among dairy cattle and to investigate the relationship between these networks and the transmission of diseases in the dairy cattle population.

Compulsivity and Inhibitory Control Deficits in Abstinent Individuals With Heroin Addiction and Their Biological Siblings Compared With Unrelated Healthy Control Participants.

BACKGROUND: Compulsivity represents the performance of persistent and repetitive acts despite negative consequences and is considered one of the critical mechanisms for drug addiction. Although compulsivity-related neurocognitive impairments have been linked to addiction, it remains unclear whether these deficits might have predated drug abuse as potential familial susceptibilities. METHODS: A large sample of 213 adult participants were recruited, including 70 abstinent individuals addicted to heroin (HAs), 69 unaffected biological siblings of the HAs (siblings), and 74 unrelated healthy control participants. Compulsivity-related neurocognitive functions were evaluated using the intradimensional/extradimensional set-shift task and a probabilistic reversal learning task. Compulsive traits were measured by the Obsessive-Compulsive Inventory-Revised. Inhibitory control was assessed using the stop signal task and Stroop Color and Word Test. Network models for group recognition were conducted using multilayer perceptron neural networks. RESULTS: Data indicated that both HAs and siblings performed worse than healthy control participants on compulsivity-related aspects (i.e., shifting and reversal learning functions) and inhibitory control and had higher levels of self-reported compulsive traits. Furthermore, neural models revealed that a possible 3-facet clustering of neurocognitive deficits was linked to both HAs and siblings. CONCLUSIONS: Our findings suggest that deficits in shift reversal and inhibitory control aspects and elevated compulsive traits, shared by HAs and their unaffected siblings, may putatively represent conceivable markers associated with familial vulnerabilities implicated in the development of heroin dependence.

A new network analysis model in anorexia nervosa patients based on self-reported eating disorder symptoms, psychological distress, and cognitive flexibility.

OBJECTIVES: Cognitive flexibility and psychological distress, such as depression and anxiety, have been implicated in the aetiology of Anorexia Nervosa (AN). Despite the known associations between eating disorder (ED) symptoms, depression, anxiety, and cognitive flexibility, the specific pathways that connect these constructs are unclear. We therefore used network analysis to examine the relationship between these symptoms in an AN sample. METHODS: One hundred and ninety-three treatment-seeking individuals diagnosed with AN (95.6% female, M = 26.89 [SD = 9.45] years old) completed self-report measures assessing depression, anxiety, cognitive flexibility, and ED symptoms. To determine each symptom's influence in the network, we calculated the expected influence. RESULTS: The two relationships with the greatest edges were those between (1) weight/shape concerns and eating/dietary restraint and (2) weight/shape concerns and psychological distress (a measure that combined depression and anxiety). Cognitive flexibility was not connected to weight/shape concerns but had negative partial associations with eating concerns/dietary restraint and psychological distress. There was also a slight, non-zero connection between eating concerns/dietary restraint and psychological distress. CONCLUSIONS: The findings underscore the importance of weight/shape, eating/dietary concerns, and psychological distress in the AN network and suggest that addressing cognitive flexibility may be a useful target for eating concerns/dietary restraint and psychological distress. Future studies assessing the longitudinal course of psychopathology within the AN network structure may help in identifying whether specific symptoms function as risk factors or maintaining factors for this co-occurrence.

Are different countries equally green with envy? A comparison of the everyday concept of envy in the United States, Spain, and Germany.

Using a prototype approach to emotion concepts, we mapped the internal structure and content of the everyday concept of envy (as used in the United States) and its translation equivalents of envidia in Spanish and Neid in German. In Study 1 (total N = 415), the features of the concept of envy, envidia, and Neid were generated via an open-ended questionnaire. In Study 2 (total N = 404), participants rated the degree of typicality of the constitutive features on a forced-choice questionnaire. The prototype analysis of envy, supplemented with network analyses, revealed that the largest connected set of features of envy, envidia, and Neid shared a group of central features, including features related to success or to people with a better appearance. Still, envy, envidia, and Neid did differ with respect to their constituent peripheral features as well as the density of their networks, their structure, and the betweenness centrality of the nodes. These results suggest that a prototype approach combined with network analysis is a convenient approach for studying the internal structure of everyday emotion concepts and the degree of overlap with respect to the translation equivalents in different countries.

Longitudinal relationship between oppositional defiant disorder symptoms and attention-deficit/hyperactivity disorder symptoms in Chinese children: insights from cross-lagged panel network analyses.

Oppositional defiant disorder (ODD) and attention-deficit/hyperactivity disorder (ADHD) are two of the most common childhood mental disorders, and they have substantial comorbidity. The developmental precursor model has long been widely used to explain the mechanisms of comorbidity between ODD and ADHD, however whether it is equally effective at the symptomatic level is unclear. Therefore, this study aimed to (a) examine the stability of the ODD and ADHD comorbidity network in a longitudinal sample of high-risk children in China; and (b) examine the longitudinal relationship between the ODD and ADHD symptom networks based on a developmental precursor model. Two hundred sixty-three Chinese children aged 6 to 13 years with ODD and/or ADHD were assessed for symptoms of ODD and ADHD in two surveys conducted 1 year apart. We used data from these two time points to construct two cross-sectional networks and a cross-lagged panel network (CLPN) to explore the symptom network for comorbidity of ODD and ADHD. The analysis shows that: (1) the two cross-sectional networks are highly similar in terms of structure, existence of edges, centrality estimates, and the invariance test shows that there is no significant difference between them. The symptoms "follow through", "interrupts/intrudes", "difficulty playing quietly" and "concentration" had the highest expected influence centrality at both time points. (2) Combined with the results of the cross-sectional and cross-lagged networks, we found that "annoy" and "blame" are potential bridge symptoms between the ODD and ADHD symptom networks. The symptom "annoy" forms a reciprocal predictive relationship with "interrupts/intrudes", while "blame" unidirectionally predicts "close attention". In addition, we found that "vindictive" predicted numerous ADHD symptoms, whereas "angry" was predicted by numerous ADHD symptoms. The findings emphasize the broad predictive relationship between ODD and ADHD symptoms with each other, and that ODD symptoms may lead to activation of the ADHD symptom network and vice versa. These findings suggest that the developmental precursor model at the symptom level may partially explain the comorbidity mechanisms of ODD and ADHD, and future studies should further investigate the underlying multiple mechanisms.

The Associations Between Parental Phubbing, Adolescent Phubbing, and Adolescents' Adjustments: A Cross-Lagged Panel Network Analysis.

A growing body of research indicates that phubbing can negatively influence adolescent development, it is not clear how perceived parental phubbing, adolescent phubbing, and adolescents' adjustment problems concurrently relate to each other at the dimension level. This study conducted the contemporaneous network analyses and cross-lagged network analysis to examine the distinct relationships between the various dimensions of perceived father phubbing, perceived mother phubbing, adolescent phubbing and adolescent's adjustment problems. A total of 1447 Chinese students (60.5% females; Mean age = 16.15, SD = 0.65) completed a survey at two-time points. The results of the contemporaneous network analyses indicated that perceived father/mother ignorance have the strongest links with the dimensions of adolescent phubbing and adolescents' adjustment problems, suggesting that adolescents who reported high levels of perceived father/mother ignorance are more likely to concurrently face other issues and thus should be a primary focus of concern. The cross-lagged panel network analysis revealed that academic burnout is the primary catalyst in this dynamic network, which underscores a child-driven effect within the network. This emphasizes the importance of addressing adolescent academic burnout as a pivotal intervention point, both to alleviate phubbing in parent-adolescent interactions and to tackle adolescents' adjustment problems.

Integrated procedures for accelerating, deepening, and leading genetic inquiry: A first application on human muscle secretome.

PURPOSE: Beyond classical procedures, bioinformatic-assisted approaches and computational biology offer unprecedented opportunities for scholars. However, these amazing possibilities still need epistemological criticism, as well as standardized procedures. Especially those topics with a huge body of data may benefit from data science (DS)-assisted methods. Therefore, the current study dealt with the combined expert-assisted and DS-assisted approaches to address the broad field of muscle secretome. We aimed to apply DS tools to fix the literature research, suggest investigation targets with a data-driven approach, predict possible scenarios, and define a workflow. METHODS: Recognized scholars with expertise on myokines were invited to provide a list of the most important myokines. GeneRecommender, GeneMANIA, HumanNet, and STRING were selected as DS tools. Networks were built on STRING and GeneMANIA. The outcomes of DS tools included the top 5 recommendations. Each expert-led discussion has been then integrated with an DS-led approach to provide further perspectives. RESULTS: Among the results, 11 molecules had already been described as bona-fide myokines in literature, and 11 molecules were putative myokines. Most of the myokines and the putative myokines recommended by the DS tools were described as present in the cargo of extracellular vesicles. CONCLUSIONS: Including both supervised and unsupervised learning methods, as well as encompassing algorithms focused on both protein interaction and gene represent a comprehensive approach to tackle complex biomedical topics. DS-assisted methods for reviewing existent evidence, recommending targets of interest, and predicting original scenarios are worth exploring as in silico recommendations to be integrated with experts' ideas for optimizing molecular studies.

Identification of SERPINA1 promoting better prognosis in papillary thyroid carcinoma along with Hashimoto's thyroiditis through WGCNA analysis.

Background: Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease. Papillary thyroid carcinoma (PTC) is the most common endocrine cancer. In recent years the rate of coexistence between PTC and HT has increased but the relationship between them remains unclear, meaning it is necessary to find potential biomarkers for PTC coexistence with HT to predict its potential pathways. Method: A co-expression network was constructed using the weighted gene co-expression network analysis (WGCNA) in the R package. The modules of PTC associated with HT (PTC-W) were identified from the GSE138198 dataset. Protein-protein interaction network (PPI) was used to screen the hub genes. Immunohistochemical (IHC) analysis was performed to validate the expression of the hub genes in tissues. Clinical data from The Cancer Genome Atlas (TCGA) datasets were used to analyse the prognosis of the hub genes. Gene set enrichment analysis (GSEA) was used to screen potential pathways of PTC-W. Result: The MEbrown module representing the most significant module, with 958 differentially expressed genes (DEGs), was screened in PTC-W, based on WGCNA analysis. Through PPI, SERPINA1 was identified as a hub gene. Immunostaining validated that SERPINA1 was highly expressed in PTC-W. Moreover, PTC-W expressing SERPINA1 exhibits a better prognosis than PTC without HT (PTC-WO). Conclusion: Our study demonstrates that SERPINA1 promotes the occurrence of PTC-W, and its prognosis is better than PTC-WO. SERPINA1 promotes a better prognosis for PTC-W, possibly through a tumour inhibition signalling pathway.

Untargeted metabolomics analysis in drug-naïve patients with severe obsessive-compulsive disorder.

Introduction: Obsessive-compulsive disorder (OCD), characterized by the presence of obsessions and/or compulsions, is often difficult to diagnose and treat in routine clinical practice. The candidate circulating biomarkers and primary metabolic pathway alteration of plasma in OCD remain poorly understood. Methods: We recruited 32 drug-naïve patients with severe OCD and 32 compared healthy controls and applied the untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to assess their circulating metabolic profiles. Both univariate and multivariate analyses were then utilized to filtrate differential metabolites between patients and healthy controls, and weighted Correlation Network Analysis (WGCNA) was utilized to screen out hub metabolites. Results: A total of 929 metabolites were identified, including 34 differential metabolites and 51 hub metabolites, with an overlap of 13 metabolites. Notably, the following enrichment analyses underlined the importance of unsaturated fatty acids and tryptophan metabolism alterations in OCD. Metabolites of these pathways in plasma appeared to be promising biomarkers, such as Docosapentaenoic acid and 5-Hydroxytryptophan, which may be biomarkers for OCD identification and prediction of sertraline treatment outcome, respectively. Conclusion: Our findings revealed alterations in the circulating metabolome and the potential utility of plasma metabolites as promising biomarkers in OCD.

Weighted gene co-expression network analysis of nitrogen (N)-responsive genes and the putative role of G-quadruplexes in N use efficiency (NUE) in rice.

Rice is an important target to improve crop nitrogen (N) use efficiency (NUE), and the identification and shortlisting of the candidate genes are still in progress. We analyzed data from 16 published N-responsive transcriptomes/microarrays to identify, eight datasets that contained the maximum number of 3020 common genes, referred to as N-responsive genes. These include different classes of transcription factors, transporters, miRNA targets, kinases and events of post-translational modifications. A Weighted gene co-expression network analysis (WGCNA) with all the 3020 N-responsive genes revealed 15 co-expression modules and their annotated biological roles. Protein-protein interaction network analysis of the main module revealed the hub genes and their functional annotation revealed their involvement in the ubiquitin process. Further, the occurrences of G-quadruplex sequences were examined, which are known to play important roles in epigenetic regulation but are hitherto unknown in N-response/NUE. Out of the 3020 N-responsive genes studied, 2298 contained G-quadruplex sequences. We compared these N-responsive genes containing G-quadruplex sequences with the 3601 genes we previously identified as NUE-related (for being both N-responsive and yield-associated). This analysis revealed 389 (17%) NUE-related genes containing G-quadruplex sequences. These genes may be involved in the epigenetic regulation of NUE, while the rest of the 83% (1811) genes may regulate NUE through genetic mechanisms and/or other epigenetic means besides G-quadruplexes. A few potentially important genes/processes identified as associated with NUE were experimentally validated in a pair of rice genotypes contrasting for NUE. The results from the WGCNA and G4 sequence analysis of N-responsive genes helped identify and shortlist six genes as candidates to improve NUE. Further, the hitherto unavailable segregation of genetic and epigenetic gene targets could aid in informed interventions through genetic and epigenetic means of crop improvement.