Search Results (23)

In this study, the vegetation of the natural area of the Göksu Delta Special Environmental Protection Agency (SEPA), one of Turkey’s most important wetlands, is researched. The importance of this study in terms of contributing to environmental protection and land use planning studies reveals that this natural area, where rare ecosystems are found, has started to degrade and disappear under human influence. This study was conducted because the area is not only a designated RAMSAR wetland (a wetland site designated of international importance especially for the Waterfowl Habitat under the Ramsar Convention) but also includes nearby residential developments. With this study, the vegetation of the area was studied to determine the syntaxonomic units across different habitats. The natural area of Göksu Delta is divided into three main habitat groups: aquatic, sand dune, and halophytic. In the research, the Braun-Blanquet method was used. During the research in the Göksu Delta, 279 sample areas were surveyed. The data were analysed according to the fuzzy means cluster method. During the investigation, 29 associations were identified, and 16 of them are considered a new finding for science. These 29 associations can be classified as follows: aquatic vegetation is represented with four associations (three of them belong to Phragmito-Magnocaricetea and one of them belongs to Potametea classes), sand dune vegetation is represented with 12 associations (belonging to Ammophiletea Br.-Bl. & Tüxen ex Westhoff, Dijk, & Passchier 1946 class), and halophytic vegetation is represented with 13 associations (six of them belong to Salicornietea fruticosae Br.-Bl. & Tüxen ex A. & O. Bolòs 1950, six of them belong to Juncetea maritimi Br.-Bl. in Br.-Bl., Roussine & Nègre 1952, and one of them belong to Molinio-Juncetea Br.-Bl. (1931) 1947 classes). Three (Onopordum boissieri, Ambrosia maritima, and Chlamydophora tridentata) of the endemics and rare plants that were explored during the study were recorded as new alliance characteristics. Full article

Type 2 diabetes (T2D) is a prevalent chronic disease in the Korean population, influenced by lifestyle, dietary habits, and genetics. This study aimed to identify the effects of food intake and genetic factors on T2D progression in Korean adults using a multi-state illness-death model. We analyzed three transition models: normal glucose tolerance (NGT) to prediabetes (PD), NGT to T2D, and PD to T2D. We first identified dietary patterns significantly associated with each transition, using multivariate Cox proportional hazards models. Then, we assessed the impact of single-nucleotide polymorphisms (SNPs) on each transition, incorporating these dietary patterns as covariates. Our analysis revealed significant associations between the identified dietary patterns and the risk of PD and T2D incidence among individuals with NGT. We also identified novel genetic variants associated with disease progression: two SNPs (rs4607517 in Glucokinase [GCK] and rs758982 in Calcium/Calmodulin-Dependent Protein Kinase II Beta [CAMK2B]) in the NGT to PD model, and eight SNPs in the NGT to T2D model, including variants in the Zinc Finger Protein 106 (ZNF106), PTOV1 Extended AT-Hook Containing Adaptor Protein (PTOV1), Proprotein Convertase Subtilisin/Kexin Type 2 (PCSK2), Forkhead Box D2 (FOXD2), Solute Carrier Family 38 Member 7 (SLC38A7), and Neuronal Growth Regulator 1 (NEGR1) genes. Functional annotation analysis using ANNOVAR revealed that rs4607517 (GCK) and rs59595912 (PTOV1) exhibited high Combined Annotation-Dependent Depletion (CADD) and Deleterious Annotation of Genetic Variants using Neural Networks (DANN) scores, suggesting potential pathogenicity and providing a functional basis for their association with T2D progression. Integrating dietary and genetic factors with a multi-state model, this comprehensive approach offers valuable insights into T2D development and highlights potential targets for prevention and personalized interventions. Full article

The IgLON family of cell adhesion molecules consists of five members (LSAMP, OPCML, neurotrimin, NEGR1, and IgLON5) discovered as supporters of neuronal development, axon growth and guidance, and synapse formation and maintenance. Tumour suppression properties have recently been emerging based on antiproliferative effects through the modulation of oncogenic pathways. Available evidence endorses a role for non-coding RNAs or microRNAs as relevant controllers of IgLON molecule expression that can impact their critical physiological and pathological roles. Current findings support a function for long non-coding RNAs and microRNAs in the modulation of LSAMP expression in cell senescence, cancer biogenesis, addiction, and pulmonary hypertension. For OPCML, data point to a role for several microRNAs in the control of tumorigenesis. MicroRNAs were detected in neurotrimin-mediated functions in cancer biogenesis and in Schwann cell responses to peripheral nerve injury. For NEGR1, studies have mainly investigated microRNA involvement in neuronal responses to ischaemic injury, although data also exist about tumorigenesis and endothelial cell dysfunction. For IgLON5, information is only available about microRNA involved in myocardial infarction. In conclusion, despite much information being still missing and further research needed, the emerging picture favours a model in which non-coding RNAs exert a crucial role in modulating IgLON expression, ultimately affecting their important physiological functions. Full article

The immunoglobulin LAMP/OBCAM/NTM (IgLON) family of cell adhesion molecules comprises five members known for their involvement in establishing neural circuit connectivity, fine-tuning, and maintenance. Mutations in IgLON genes result in alterations in these processes and can lead to neuropsychiatric disorders. The two IgLON family members NEGR1 and OPCML share common links with several of them, such as schizophrenia, autism, and major depressive disorder. However, the onset and the underlying molecular mechanisms have remained largely unresolved, hampering progress in developing therapies. NEGR1 and OPCML are evolutionarily conserved in teleosts like the zebrafish (Danio rerio), which is excellently suited for disease modelling and large-scale screening for disease-ameliorating compounds. To explore the potential applicability of zebrafish for extending our knowledge on NEGR1- and OPCML-linked disorders and to develop new therapeutic strategies, we investigated the spatio-temporal expression of the two genes during early stages of development. negr1 and opcml are expressed maternally and subsequently in partially distinct domains of conserved brain regions. Other areas of expression in zebrafish have not been reported in mammals to date. Our results indicate that NEGR1 and OPCML may play roles in neural circuit development and function at stages earlier than previously anticipated. A detailed functional analysis of the two genes based on our findings could contribute to understanding the mechanistic basis of related psychiatric disorders. Full article

‘Sobrassada de Mallorca’ is an EU PGI (Protected Geographical Indication) -qualified traditional food with important historical, social, and gastronomical relevance. However, its nutritional features are poorly characterized. Here, we studied 15 samples of Sobrassada de Mallorca (SM) and 9 samples of ‘Sobrassada de Mallorca de Porc Negre’ (SMBP), which are the two types of sobrassada that are PGI-protected. Their composition was assessed under the light of the EU Regulation 1924/2006 on nutrition and health claims (NHC) made on food. Results show the notably high energetic density (588 and 561 kcal/100 g for SM and SMBP, respectively) due to the notable fatty acid (FA) content and the relatively high proportion of unsaturated FAs (≈61% of total FAs) is also noted, mainly oleic acid (39.7 and 45.7%). Moreover, analyses showed that 100 g of both types of ‘Sobrassada de Mallorca’ present a ‘significant’ content (at least 15% of the established Nutrient Reference Values) of vitamins A (241 and 232 µg), E (2.67 and 2.67 mg), B₃ (3.50 and 2.43 mg), B₆ (0.27 and 0.35 mg), B₁₂ (0.65 and 0.56 µg), phosphorus (271 and 186 mg), and selenium (17.3 and 16.2 µg) as defined by the EU standards and, in essence, their associated health benefits can be claimed for both SM and SMBP or foods containing them. In principle, SM and SMBP could be associated with various health claims (HC), including those related to energy-yielding metabolism, normal functioning of the immune system, and reduction of tiredness and fatigue. Full article

In the brain, cell adhesion molecules (CAMs) are critical for neurite outgrowth, axonal fasciculation, neuronal survival and migration, and synapse formation and maintenance. Among CAMs, the IgLON family comprises five members: Opioid Binding Protein/Cell Adhesion Molecule Like (OPCML or OBCAM), Limbic System Associated Membrane Protein (LSAMP), neurotrimin (NTM), Neuronal Growth Regulator 1 (NEGR1), and IgLON5. IgLONs exhibit three N-terminal C2 immunoglobulin domains; several glycosylation sites; and a glycosylphosphatidylinositol anchoring to the membrane. Interactions as homo- or heterodimers in cis and in trans, as well as binding to other molecules, appear critical for their functions. Shedding by metalloproteases generates soluble factors interacting with cellular receptors and activating signal transduction. The aim of this review was to analyse the available data implicating a role for IgLONs in neuropsychiatric disorders. Starting from the identification of a pathological role for antibodies against IgLON5 in an autoimmune neurodegenerative disease with a poorly understood mechanism of action, accumulating evidence links IgLONs to neuropsychiatric disorders, albeit with still undefined mechanisms which will require future thorough investigations. Full article

Neuroblastoma is among the most common childhood cancers. Neuroblastoma in advanced stages is one of the most intractable pediatric cancers, notwithstanding the recent therapeutic advances. ALK mutations are among the leading cause of hereditary neuroblastoma and account for more than 14% of the somatically acquired alterations. ALK kinase activity is currently one of the main targets for pharmacological strategies. However, evidence from ALK fusion-positive lung cancer studies has shown that resistance to ALK inhibition arises during the therapy, causing a relapse within several years. IgLONs are membrane-bound proteins involved in cell-to-cell adhesion. The expression of the IgLON family results altered in different cancers. We found that the IgLON member Negr1 is downregulated in neuroblastoma. The ectopic overexpression of Negr1 impairs neuroblastoma growth in vitro and in vivo. Negr1 exists as a GPI-anchored membrane-bound protein and as a soluble protein released upon metalloprotease cleavage. We generated and characterized a panel of Negr1-derived peptides. The treatment with Negr1 protein and derived peptides induce ALK downregulation and halt neuroblastoma progression in vitro and in vivo. Full article

With a perspective future ban on surgical castration in Europe, selecting pigs with reduced ability to accumulate boar taint (BT) compounds (androstenone, indole, skatole) in their tissues seems a promising strategy. BT compound concentrations were quantified in the adipose tissue of 1075 boars genotyped at 29,844 SNPs. Traditional and SNP-based breeding values were estimated using pedigree-based BLUP (PBLUP) and genomic BLUP (GBLUP), respectively. Heritabilities for BT compounds were moderate (0.30–0.52). The accuracies of GBLUP and PBLUP were significantly different for androstenone (0.58 and 0.36, respectively), but comparable for indole and skatole (~0.43 and ~0.47, respectively). Several SNP windows, each explaining a small percentage of the variance of BT compound concentrations, were identified in a genome-wide association study (GWAS). A total of 18 candidate genes previously associated with BT (MX1), reproduction traits (TCF21, NME5, PTGFR, KCNQ1, UMODL1), and fat metabolism (CTSD, SYT8, TNNI2, CD81, EGR1, GIPC2, MIGA1, NEGR1, CCSER1, MTMR2, LPL, ERFE) were identified in the post-GWAS analysis. The large number of genes related to fat metabolism might be explained by the relationship between sexual steroid levels and fat deposition and be partially ascribed to the pig line investigated, which is selected for ham quality and not for lean growth. Full article

In GWAS studies, the neural adhesion molecule encoding the neuronal growth regulator 1 (NEGR1) gene has been consistently linked with both depression and obesity. Although the linkage between NEGR1 and depression is the strongest, evidence also suggests the involvement of NEGR1 in a wide spectrum of psychiatric conditions. Here we show the expression of NEGR1 both in tyrosine- and tryptophan hydroxylase-positive cells. Negr1^−/− mice show a time-dependent increase in behavioral sensitization to amphetamine associated with increased dopamine release in both the dorsal and ventral striatum. Upregulation of transcripts encoding dopamine and serotonin transporters and higher levels of several monoamines and their metabolites was evident in distinct brain areas of Negr1^−/− mice. Chronic (23 days) escitalopram-induced reduction of serotonin and dopamine turnover is enhanced in Negr1^−/− mice, and escitalopram rescued reduced weight of hippocampi in Negr1^−/− mice. The current study is the first to show alterations in the brain monoaminergic systems in Negr1-deficient mice, suggesting that monoaminergic neural circuits contribute to both depressive and obesity-related phenotypes linked to the human NEGR1 gene. Full article

Parkinson’s disease (PD) is a neurodegenerative disease with an impairment of movement execution that is related to age and genetic and environmental factors. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to induce PD models, but the effect of MPTP on the cells and genes of PD has not been fully elucidated. By single-nucleus RNA sequencing, we uncovered the PD-specific cells and revealed the changes in their cellular states, including astrocytosis and endothelial cells’ absence, as well as a cluster of medium spiny neuron cells unique to PD. Furthermore, trajectory analysis of astrocyte and endothelial cell populations predicted candidate target gene sets that might be associated with PD. Notably, the detailed regulatory roles of astrocyte-specific transcription factors Dbx2 and Sox13 in PD were revealed in our work. Finally, we characterized the cell–cell communications of PD-specific cells and found that the overall communication strength was enhanced in PD compared with a matched control, especially the signaling pathways of NRXN and NEGR. Our work provides an overview of the changes in cellular states of the MPTP-induced mouse brain. Full article

In 2021, over 100,000 people died prematurely from opioid overdoses. Neuropsychiatric and cognitive impairments are underreported comorbidities of reward dysregulation due to genetic antecedents and epigenetic insults. Recent genome-wide association studies involving millions of subjects revealed frequent comorbidity with substance use disorder (SUD) in a sizeable meta-analysis of depression. It found significant associations with the expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others. However, despite the rise in SUD and neuropsychiatric illness, there are currently no standard objective brain assessments being performed on a routine basis. The rationale for encouraging a standard objective Brain Health Check (BHC) is to have extensive data available to treat clinical syndromes in psychiatric patients. The BHC would consist of a group of reliable, accurate, cost-effective, objective assessments involving the following domains: Memory, Attention, Neuropsychiatry, and Neurological Imaging. Utilizing primarily PUBMED, over 36 years of virtually all the computerized and written-based assessments of Memory, Attention, Psychiatric, and Neurological imaging were reviewed, and the following assessments are recommended for use in the BHC: Central Nervous System Vital Signs (Memory), Test of Variables of Attention (Attention), Millon Clinical Multiaxial Inventory III (Neuropsychiatric), and Quantitative Electroencephalogram/P300/Evoked Potential (Neurological Imaging). Finally, we suggest continuing research into incorporating a new standard BHC coupled with qEEG/P300/Evoked Potentials and genetically guided precision induction of “dopamine homeostasis” to diagnose and treat reward dysregulation to prevent the consequences of dopamine dysregulation from being epigenetically passed on to generations of our children. Full article

The objective of this study was to uncover genomic regions explaining a substantial proportion of the genetic variance in milk production traits and somatic cell score in a Valle del Belice dairy sheep. Weighted single-step genome-wide association studies (WssGWAS) were conducted for milk yield (MY), fat yield (FY), fat percentage (FAT%), protein yield (PY), protein percentage (PROT%), and somatic cell score (SCS). In addition, our aim was also to identify candidate genes within genomic regions that explained the highest proportions of genetic variance. Overall, the full pedigree consists of 5534 animals, of which 1813 ewes had milk data (15,008 records), and 481 ewes were genotyped with a 50 K single nucleotide polymorphism (SNP) array. The effects of markers and the genomic estimated breeding values (GEBV) of the animals were obtained by five iterations of WssGBLUP. We considered the top 10 genomic regions in terms of their explained genomic variants as candidate window regions for each trait. The results showed that top ranked genomic windows (1 Mb windows) explained 3.49, 4.04, 5.37, 4.09, 3.80, and 5.24% of the genetic variances for MY, FY, FAT%, PY, PROT%, and total SCS, respectively. Among the candidate genes found, some known associations were confirmed, while several novel candidate genes were also revealed, including PPARGC1A, LYPLA1, LEP, and MYH9 for MY; CACNA1C, PTPN1, ROBO2, CHRM3, and ERCC6 for FY and FAT%; PCSK5 and ANGPT1 for PY and PROT%; and IL26, IFNG, PEX26, NEGR1, LAP3, and MED28 for SCS. These findings increase our understanding of the genetic architecture of six examined traits and provide guidance for subsequent genetic improvement through genome selection. Full article

Neuronal growth regulator 1 (NEGR1) is a brain-enriched membrane protein that is involved in neural cell communication and synapse formation. Accumulating evidence indicates that NEGR1 is a generic risk factor for various psychiatric diseases including autism and depression. Endoglycosidase digestion of single NEGR1 mutants revealed that the wild type NEGR1 has six putative N-glycosylation sites partly organized in a Golgi-dependent manner. To understand the role of each putative N-glycan residue, we generated a series of multi-site mutants (2MT–6MT) with additive mutations. Cell surface staining and biotinylation revealed that NEGR1 mutants 1MT to 4MT were localized on the cell surface at different levels, whereas 5MT and 6MT were retained in the endoplasmic reticulum to form highly stable multimer complexes. This indicated 5MT and 6MT are less likely to fold correctly. Furthermore, the removal of two N-terminal sites N75 and N155 was sufficient to completely abrogate membrane targeting. An in vivo binding assay using the soluble NEGR1 protein demonstrated that glycans N286, N294 and N307 on the C-terminal immunoglobulin-like domain play important roles in homophilic interactions. Taken together, these results suggest that the N-glycan moieties of NEGR1 are closely involved in the folding, trafficking, and homodimer formation of NEGR1 protein in a site-specific manner. Full article

In this study, we hypothesized that complex early-life environments enhance the learning ability and the hippocampal plasticity when the individual is faced with future life challenges. Chicks were divided into a barren environment group (BG), a litter materials group (LG), and a perches and litter materials group (PLG) until 31 days of age, and then their learning abilities were tested following further rearing in barren environments for 22 days. In response to the future life challenge, the learning ability showed no differences among the three groups. In the hippocampal KEGG pathways, the LG chicks showed the downregulation of neural-related genes neuronal growth regulator 1 (NEGR1) and neurexins (NRXN1) in the cell adhesion molecules pathway compared to the BG (p < 0.05). Immune-related genes TLR2 in Malaria and Legionellosis and IL-18 and IL18R1 in the TNF signaling pathway were upregulated in the LG compared to in the BG (p < 0.05). Compared to the BG, the PLG displayed upregulated TLR2A in Malaria (p < 0.05). The PLG showed upregulated neural-related gene, i.e., neuronal acetylcholine receptor subunit alpha-7-like (CHRNA8) in the nicotine addiction pathway and secretagogin (SCGN) gene expression, as compared to the LG (p < 0.05). In conclusion, early-life environmental complexities had limited effects on the learning ability in response to a future life challenge. Early-life perches and litter materials can improve neural- and immune-related gene expression and functional pathways in the hippocampus of chicks. Full article

Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14), p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors. Full article