Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations the role of nutrients, vitamins, and in general, the foodborne associated background as part of the events leading ultimately to chromosome nondisjunction has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes, the possible association of DS development with maternal gut microbiota should require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa and hence, we might find associations between the use of different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N=30). Utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the prevalence of people living with DS estimated for 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

Glycosaminoglycans (GAGs) with unique structures from marine animals show intriguing pharmacological activities and negligible biological risks, providing more options for us to explore safer agents. Swim bladder is a tonic food and folk medicine, and its GAGs show good anticoag-ulant activity. In this study, two GAGs SJG-1.0 and GMG-1.0 have been extracted and isolated from the swim bladder of Sphyraena jello and Gadus morhua. The physicochemical properties, pre-cise structural characteristics, and anticoagulant activities of these GAGs were determined. The analysis results of the SJG-1.0 and GMG-1.0 showed that they were chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains with molecular weights of 109.32 kDa and 123.13 kDa, respectively. They were mainly composed of the repeating disaccharide unit of -{IdoA-α1,3-GalNAc4S-β1,4-}- (DS-A). The DS-B disaccharide unit of -{IdoA2S-α1,3-GalNAc4S-β1,4-}- also existed in both SJG-1.0 and GMG-1.0. SJG-1.0 had a higher proportion of CS-O disaccharide unit -{-GlcA-β1,3-GalNAc-β1,4-}-, while GMG-1.0 contained higher proportion of CS-E disaccha-ride unit -{-GlcA-β1,3-GalNAc4S6S-β1,4-}-. The disaccharide compositions of the GAGs varied in a species-specific manner. Anticoagulant activity assay revealed that both SJG-1.0 and GMG-1.0 had potent anticoagulant activity, which can significantly prolong activated partial thrombosis time. GMG-1.0 also can prolong the thrombin time. SJG-1.0 showed no intrinsic tenase inhibition ac-tivity, while GMG-1.0 can obviously inhibit intrinsic tenase with EC50 of 58 nM. Their significantly different anticoagulant activities may be due to their different disaccharide structural units and proportions. These findings suggested that the swim bladder CS/DS hybrid chains with well-defined structure may be safer anticoagulants with low bleeding risk.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

Disgust evolved as a way to protect one’s self from illness. DS-R measures disgust propensity of three kinds of disgust (Core, Animal Reminder and Contamination). Although the DS-R scale was refined mainly with young and largely female student population its impact on educational orientation has not been assessed. In the present study we examined the DS-R scoring and the choice of postgraduate studies in medical (n= 94) and psychology (n= 97) students. They responded to an anonymous web-based survey and completed the DS-R and a questionnaire on their demographics and plans for postgraduate studies. Female students outnumbered males (3:1) and scored higher in Total DS-R score (median: 59 vs. 50, p<0.05). Psychology students scored higher in all three kinds of disgust (p<0.05), indicating a higher level of disease avoidance. Medical students willing to follow Internal Medicine scored higher in Core Disgust (p<0.05) while psychology students willing to study Experimental Psychology scored lower in Animal Reminder subscale (p<0.001). Also, the higher the psychology students scored in Core Disgust scale the higher was the probability to choose Experimental Psychology. In conclusion, disgust propensity as rated by DS-R differentiates medical from psychology students and is also related to orientation preferences in postgraduate studies.

Castleman disease (CD) rarely presents with obstructive jaundice, which poses a diagnostic and therapeutic challenge to the management of the disease. A 40-year-old man was referred to our hospital for emergent management of upper abdominal pain. An abdominal mass was removed, and the postoperative pathology showed retroperitoneum CD, which was subsequently managed by adjuvant therapy of combination chemotherapy and steroids. One month later, a biliary metal stent was placed due to the presentation of obstructive jaundice. After approximately 3 months, the patient experienced another episode of obstructive jaundice, and SpyGlass DS cholangioscopy (Boston Scientific, Natick, Mass, USA) was performed via the biliary track for biopsy, which pathologically showed biliary malignancies. Radiofrequency ablation was performed with a probe (EMcision, Montreal, Canada), and another uncovered metal stent was placed within the existing metal stent. No stent occlusion occurred during a 6-month follow-up period. In conclusion, CD rarely presents with obstructive jaundice, and a combination of radiofrequency ablation with metal stent implantation under cholangioscopy can prolong the stent patency time and the survival time of patients.

. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.

Background and Objectives: Cardiovascular events are the leading cause of morbidity and mortal-ity in hemodialysis (HD) patients. Identifying risk factors can help in the effort to reduce cardi-ovascular risk and improve life expectancy. The purpose of this study was to evaluate the ability of CHA2DS2-VASc score [risk index of stroke in atrial fibrillation (AF)] in patients with end stage kidney disease, to predict stroke, major cardiovascular events and mortality. Materials and Meth-ods: CHA2DS2-VASc and HAS-BLED (bleeding risk from use of anticoagulation in AF) scores were calculated in 237 HD patients, [99 women, median age 76 (15) years], at time they com-menced on HD. The scores’ ability to predict long term cardiovascular morbidity and mortality was estimated, both in those with and without AF. Results: CHA2DS2-VASc score was signifi-cantly increased in AF (n=69) compared to non-AF (n=168) patients, 5 (2.5) versus 4 (2), p<0.0001, respectively. Increased CHA2DS2-VASc score was associated with heart failure (p=0.007, p=0.024), stroke (p<0.0001, p<0.0001) and risk of all-cause mortality (p<0.0001, p<0.0001), in both groups, respectively. C statistics indicated that CHA2DS2-VASc score performed modest discrimination in this HD population with and without AF for heart failure, stroke, and all-cause mortality, but for cardiovascular mortality in AF group only. Conclusions: Increased CHA2DS2-VASc score at time starting on HD, can predict stroke, heart failure and all-cause mortality in HD patients in-dependent of the presence of AF. Risk of cardiovascular mortality could be predicted only on patients with AF.

The transition to reproduction is a crucial step in the life cycle of any organism. In Arabidopsis thaliana the establishment of reproductive growth can be divided into two phases: Firstly, cauline leaves with axillary meristems are formed and internode elongation begins. Secondly, lateral meristems develop into flowers with defined organs. Floral shoots are usually determinate and suppress the development of lateral shoots. Here, we describe a transposon insertion mutant in the Nossen accession with defects in floral development and growth. Most strikingly is the outgrowth of stems from the axillary bracts of the primary flower carrying secondary flowers. Therefore, we named this mutant flower-in-flower (fif). However, the transposon insertion in the annotated gene is not the cause for the fif phenotype. By means of classical and genome sequencing-based mapping, the mutation responsible for the fif phenotype was found to be in the LEAFY gene. The mutation, a G-to-A exchange in the second exon of LEAFY, creates a novel lfy allele and results in a cysteine-to-tyrosine exchange in the α1-helix of LEAFY´s DNA-binding domain. This exchange abolishes target DNA-binding, whereas subcellular localization and homomerization are not affected. To explain the strong fif phenotype against this molecular findings, several hypotheses are discussed.

Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/3500 boys globally, characterized by progressive muscle breakdown and eventual death with an average lifespan in the mid-late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.

Nodule bacteria (rhizobia) represent a suitable model to address a range of evolutionary prob-lems including the tradeoff between genetic polymorphism and natural selection. Rhizobia possess the complicated genomes in which symbiotically specialized (sym) genes differ in their natural histories from core genes encoding for housekeeping functions. Diversification of sym genes is responsible for the rhizobia microevolution which depends on the host-induced natural selection. For the rhizobia speciation, diversification of core genes is responsible for which the selective factors are unclear. In this paper we demonstrate that in the goats’ rue rhizobia (Neorhizobium galegae) populations collected at North Caucasus and composed of two host-specific biovars orientalis and officianalis (N2-fixing symbionts of Galega orientalis and G. officinalis, respectively), evolutionary mechanisms are different for core and sym genes. In both N. galegae biovars, core genes are more polymorphic than sym genes. In bv. orientalis, evolution of core genes occurs under the impacts of driving se-lection (dN/dS > 1), while evolution of sym genes is close to neutral (dN/dS ≈ 1). In bv. officinalis, evolution of core genes is neutral, while for sym genes, it is dependent on purifying selection (dN/dS < 1). A marked phylogenetic congruence of core and sym genes revealed using the ANI analysis may be due to a low intensity of gene transfer within and between N. galegae biovars. Polymorphism of both gene groups and the impacts of driving selection on the core gene evolu-tion are more pronounced in bv. orientalis than in bv. officianalis reflecting the diversities of re-spective host plant species. In bv. orientalis, highly significant (P0 < 0,001) positive correlation was revealed between the p-distance and dN/dS values for core genes, while in bv. officinalis this cor-relation is lowly significant (0,05 < P0 < 0,10). For sym genes, correlation between the p-distance and dN/dS values is negative in bv. officinalis but is not revealed in bv. orientalis. These data along with the functional annotation of core genes implemented using the Gene Ontology tools sug-gests that evolution of bv. officinalis is based mostly on adaptation for in planta niches while in bv. orientalis evolution presumable depends on adaptation for soil niches. New insights into the tradeoff between natural selection and genetic diversity are presented suggesting that the gene polymorphism may be extended by driving selection only in the ecologically versatile organ-isms capable to support a broad spectrum of gene alleles in their genepools.