Genetic Analysis (Norway)

Both preclinical and clinical studies have revealed the indisputable importance of intestinal bacterial community composition in pathogenesis of various disease states, from obesity to neurodegeneration. Diet remains one of the most important factors shaping human intestinal microbiota composition. In this study, we investigated diet-microbiome interactions in a healthy cohort of 88 participants from Atlanta and Calgary. We examine microbial composition (16S rRNA sequencing) with dietary records using Spearman Correlation tests with Benjamini-Hochberg multiple hypothesis correction to make community-level comparisons between dietary scores and microbial diversity index scores. Predictive models were used for molecular-level comparisons between microbial gene pathways and molecules. Among generalized dietary and microbial indices, we identified a negative association between dietary whole grain consumption and a microbial dysbiosis score. Comparisons between dietary food groups and bacterial family abundance reveal significant associations between dairy consumption and Lactobacillaceae abundance, dietary unsaturated to saturated fatty acid ratio and Clostridia Cluster Family XIII, salt intake and Lachnospiraceae, and consumption of ‘greens and beans’ and Veillonellaceae. Predictive models of microbial gene pathways and molecules reveal significant positive associations between several dietary fatty acids and microbial short-chain fatty acid fermentation pathways, and between dietary lignans and archaeal methanogenesis pathways. Overall, these associations may inform future explorations on specific dietary interventions to impact the gut microbiome.

To better understand the potential health threats and underlying visual pathways of long-term light at night (LAN) exposure, we adopted a widely accepted diurnal animal model tree shrew (Tupaia belangeri chinensis), which is a close relative to primates, and evaluated the deleterious effects of long-term LAN exposure. We used an early-night LAN paradigm that was established in mice to examine behavioral and physiological consequences in adult male tree shrews. We found that 3-wk LAN exposure significantly impaired the mood and long-term memory of tree shrews without affecting the general activity pattern. We identified retinal projections to the perihabenular nucleus (pHb), a crucial area in LAN-induced negative mood, and demonstrated that the pHb continues to innervate the nucleus accumbens (NAc) in tree shrews. Moreover, the pHb was required for the LAN effect on mood but not long-term memory. Transcriptomic profiling of brain tissues containing the NAc area revealed drastic changes of several depression-related genes in NAc neurons post-LAN treatment, suggesting that long-term exposure to nighttime light could result in lasting changes in tree shrews. Collectively, we present behavioral and neural structural evidence that LAN exerts depression-inducing effects in diurnal animals via a pHb-related visual pathway, which may facilitate the translation from laboratory findings of excessive LAN exposure to clinical applications in humans.

The bitterling species, Acheilognathus majusculus, is a freshwater fish, endemic to the Nakdong and Seomjin rivers in South Korea and listed as an endangered species by the Ministry of Environment in South Korea due to its biological, ecological, and genetic importance. Dietary information is crucial for understanding the role of A. majusculus within an ecosystem and planning its restoration strategy. In this study, we employed a non-invasive DNA metabarcoding approach to characterize the diet using 34 A. majusculus fecal samples collected from the Nakdong and Seomjin rivers. Analysis of 1642037 clean reads generated by applying the next generation sequencing yielded 210 amplicon sequence variants (ASVs). Taxonomic assignment successfully identified 10 phyla, 16 classes, 23 orders, 29 families, 29 genera, and 26 species. Green algae (Chlorophyta) and diatoms (Bacillariophyta) were predominantly detected in all samples, with percentages ranging from 5.56 to 43.59% and 30.00 to 66.67%, respectively. Smaller percentages of other taxa such as parasitic protists of Ichthyosporea (Opisthokonta incertae sedis), ciliates (Ciliophora), mostly eustigmatophytes (Ochrophyta), fungi (Ascomycota), vertebrates (Chordata), flatworms (Platyhelminthes), and green plants (Streptophyta) were also detected. The dietary composition of A. majusculus remained consistent irrespective of body size or sex. However, there was pronounced seasonal variation between summer samples and those from spring and fall, as demonstrated by beta-diversity analyses. These findings provide valuable insights into the dietary composition and seasonal variations of A. majusculus and highlight the need to protect and restore aquatic habitats and regulate water flow from weirs to ensure the consistent availability of essential food resources for effective habitat management strategies of this endangered species.

The mineral compound Luvos Healing Earth (LHE) is a commercially available remedy empirically used for a variety of gastrointestinal disorders. The aim of this study was to investigate the possible effect of prolonged LHE therapy on gut microbiota in healthy individuals and in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). In this prospective exploratory study, a total of 20 participants, including 12 healthy controls and 8 patients with IBS-D, received treatment with LHE (Magenfein Granulat, 1 sachet bid) for 6 weeks. Fecal samples were collected for microbiota analysis in the morning fasting state at regular intervals at 6 different timepoints: 2 weeks before starting therapy (Screen), and every 2 weeks during LHE therapy (V0-V3). Additionally, a follow-up visit was scheduled 4 weeks after the end of treatment (V4). Microbiota analysis was performed using the GA-map® Dysbiosis Test Lx v2. Dysbiosis Index, bacterial diversity, as well as the balance or imbalance of functionally important bacteria were assessed. The microbiota analysis revealed an overlap in gut microbiota profiles between healthy controls and patients with IBS-D. Bacterial communities were consistently stable during the entire treatment period, and no significant variations in composition were observed 4 weeks after the end of the therapeutic intervention. There was a remarkable stability of microbiota profiles over time within each individual and a high inter-individual variation. The majority of fecal samples exhibited profiles, reflecting an eubiotic state, with no significant changes in dysbiosis index, functional bacteria profiles, or bacterial diversity. Our findings indicate intraindividual resilience of microbiota consortia during the entire study period. Prolonged intake of LHE does not cause significant alterations in fecal microbiota profiles in healthy controls and patients with IBS-D. Luvos Healing Earth does not affect the stability of gut microbial diversity and bacterial functions.

The molecular basis of programmed cell death and neuroinflammation in neurodegenerative diseases The pathogenesis of neurodegenerative diseases is closely linked to the occurrence of programmed cell death, also known as apoptosis and neuroinflammation. Despite the presence of a distinct mode of cell death exhibiting unique morphological characteristics, the identification and implications of this phenomenon in neurological diseases remain unknown. Current scientific investigations are diligently striving to identify and understand distinct cellular and molecular targets that can be selectively engaged in therapeutic intervention for Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). This special edition is dedicated to a diverse array of original research, comprehensive literature reviews, and expert opinions that its aim is to provide a deeper understanding of the intricate molecular mechanisms underlying programmed cell death in the context of neurodegenerative disorders. The perspective article from Zhang et al. presents a comprehensive analysis of the landscape of necroptosis research spanning the period from 2012 to 2021. The investigation of necroptosis has exhibited a sustained and consistent expansion throughout the previous decade. The current focus of research revolves around the phenomenon of synergistic interactions with ferroptosis, with an increasing emphasis on the exploration of RIPK1/ RIPK3/MLKL pathways. This line of investigation aims to elucidate the intricate connections between ferroptosis, inflammation, and oxidative stress while also exploring the translational applications and therapeutic prospects for combating cancer and neurological disorders. The seminal study conducted by Lee et al. introduced a chronic constriction injury (CCI) model as an effective animal model for investigating neuropathic pain. Their research Frontiers in Immunology frontiersin.org 01

Introduction: X chromosome architecture and integrity are essential for normal ovarian function. Both numerical and structural X chromosome abnormalities play an important role in female infertility. This study aimed to determine the types and frequency of X chromosome aberrations detected in women referred for cytogenetic investigation due to reproductive problems. Methods: 2,936 women (average age: 37.5 years) were enrolled in the present study. Peripheral blood karyotyping was performed by conventional cytogenetic techniques. For each woman, 20 G-banded metaphases were studied and in case of suspected mosaicism, analysis was extended to 100 metaphases. Results: 2,588/2,936 (88.15%) of women had a normal karyotype (46,XX), while 348/2,936 (11.85%) had an abnormal one. Thirty-two women (1.09%) carried autosomal chromosome abnormalities and 316 (10.76%) had X chromosome rearrangements. In 311/2,936 women (10.59%), X chromosome numerical aberrations were detected (low-level mosaicism), and in 5/2,936 cases (0.17%), X structural abnormalities (two with pericentric inversion, one with Xq deletion and two 45,X mosaics, one with an Xp deletion cell line and the other with isochromosome Xq cell line). Low-level X mosaicism was a common finding in women >35 years as compared to younger ones (92.93% vs. 7.07%), a finding consistent with loss of chromosome X with aging. Other X chromosome abnormalities were detected in younger women (32.3 ± 4.13 vs. 41.04 ± 4.5 years). The mean age of women with Turner-like phenotype was 28.75 ± 6.6 years. Conclusion: The study confirms that the incidence of X chromosome abnormalities is increased in women with fertility problems and that karyotype is the gold standard for their identification. Genetic counseling is recommended in these cases to provide information concerning available treatment and fertility options.

Constitutive activation of the PI3K/AKT/mTOR-pathway plays an important role in the pathogenesis of mantle cell lymphoma (MCL), leading to approval of the mTOR inhibitor temsirolimus for relapsed or refractory MCL. Yet, despite favorable initial response rates, early relapses under treatment have been observed. Therefore, understanding the underlying mechanisms of temsirolimus resistance and developing strategies to overcome it is highly warranted. Here, we established a new temsirolimus-resistant MCL cell line to evaluate the molecular background of resistance to this drug. Transcriptome profiling and gene set enrichment analysis comparing temsirolimus-sensitive and -resistant cell lines showed significant upregulation of PI3K/AKT/mTor-, RAS signaling- and the RTK-dependent PDGFR-, FGFR-, Met- and ALK-signaling-pathways in the resistant cells. Furthermore, MET, known as important proto-oncogene and mediator of drug resistance, was among the most upregulated genes in the resistant cells. Importantly, Met protein was overexpressed in both, MCL cells with acquired as well as intrinsic temsirolimus resistance, but could not be detected in any of the temsirolimus sensitive ones. Combined pharmacological inhibition of mTOR and Met signaling with temsirolimus and the RTK inhibitor crizotinib significantly restored sensitivity to temsirolimus. Furthermore, this combined treatment proved to be synergistic in all MCL cell lines investigated and was also active in primary MCL cells. In summary, we showed for the first time that overexpression of MET plays an important role for mediating temsirolimus resistance in MCL and combined treatment with temsirolimus and crizotinib is a very promising therapeutic approach for MCL and an effective strategy to overcome temsirolimus resistance.

Two putative long noncoding RNAs in zebrafish encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, which are required for development of vertebrate-specific brain cell types.