Miracle-dz/UniFAR-FTUs huggingface dataset:
Introducing Beneficial Alleles from Plant Genetic Resources into the Wheat Germplasm

Simple Summary Many crops including wheat have a narrow genetic base after hundreds of years of breeding and selection. This makes it difficult to breed new varieties with increased yields to feed the growing global population, and with stronger tolerance to the wider range of biotic and abiotic stresses that are anticipated with climate change. Thus, there is a need to introduce new genetic diversity into wheat breeding programs. Plant genetic resources stored in genebanks and the wild relatives of crops are potential sources of new genetic diversity. Here, we discuss the importance of these resources for breeding new wheat cultivars, and outline where they are currently stored and used. We also discuss pre-breeding, where genetic regions associated with desirable traits are identified and transferred into materials ready for use in breeding programs. Pre-breeding in wheat, when conducted in close collaboration with breeders, farmers, and end-users, has contributed to many outstanding varieties and novel beneficial diversity. This review addresses various genetic and genomic considerations for the strategic transfer of this useful diversity. Abstract Wheat (Triticum sp.) is one of the world’s most important crops, and constantly increasing its productivity is crucial to the livelihoods of millions of people. However, more than a century of intensive breeding and selection processes have eroded genetic diversity in the elite genepool, making new genetic gains difficult. Therefore, the need to introduce novel genetic diversity into modern wheat has become increasingly important. This review provides an overview of the plant genetic resources (PGR) available for wheat. We describe the most important taxonomic and phylogenetic relationships of these PGR to guide their use in wheat breeding. In addition, we present the status of the use of some of these resources in wheat breeding programs. We propose several introgression schemes that allow the transfer of qualitative and quantitative alleles from PGR into elite germplasm. With this in mind, we propose the use of a stage-gate approach to align the pre-breeding with main breeding programs to meet the needs of breeders, farmers, and end-users. Overall, this review provides a clear starting point to guide the introgression of useful alleles over the next decade.
Wearing Cushioning Shoes Reduce Load Rates More Effectively in Post-Fatigue than in Pre-Fatigue during Landings

Simple Summary Athlete experience high impact forces during landing, which is a contributing factor to injury risk potentials. As a potential factor of affecting the impact force, previous study of the effects of footwear cushioning effect on landing biomechanics were inconsistent. Furthermore, limited efforts have been exerted on the relationship between footwear cushioning and fatigue. In this study, the footwear cushioning effects on bipedal landing biomechanics before and after acute exercise-induced fatigue protocol were explored. The results of this study suggest that footwear cushioning can reduce landing-related rearfoot impact forces regardless of fatigue conditions. In a situation where the neuromuscular activity is reduced or absent, e.g., post-fatigue, wearing better cushioning shoes show superior attenuation, as indicated by low forefoot and rearfoot impacts. Abstract Purpose: this study aimed to investigate the footwear cushioning effects on impact forces and joint kinematics of the lower extremity during bipedal drop landings before and after acute exercise-induced fatigue protocol. Methods: in this case, 15 male collegiate basketball athletes performed drop landings from a 60 cm platform wearing highly-cushioned shoes (HS) and less cushioned shoes (control shoes, CS) before and after acute fatigue-inducing exercises (i.e., shuttle run combined with multiple vertical jumps). Force plates and motion capturing systems were synchronised to measure ground reaction forces and kinematic data during drop landings. Maximum jump height was analysed with one-way ANOVA. Two-way repeated measure ANOVAs were performed on each of the tested variables to examine if there was significant main effects of shoe and fatigue as well as the interaction. The significance level was set to 0.05. Results: rearfoot peak impact forces and loading rates significantly reduced when the participants wore HS in pre- and post-fatigue conditions. The peak loading rates in forefoot significantly reduced when HS were worn in post-fatigue. Compared with pre-fatigue, wearing HS contributed to with 24% and 13% reduction in forefoot and rearfoot peak loading rates, respectively, and the occurrence times of first and second peak impact forces and loading rates were much later. In the post-fatigue, a significant increase in the initial contact and minimum angles of the ankle were observed in HS compared with CS. Conclusion: these findings suggest that footwear cushioning can reduce landing-related rearfoot impact forces regardless of fatigue conditions. In a situation where the neuromuscular activity is reduced or absent such as post-fatigue wearing better cushioning shoes show superior attenuation, as indicated by lower forefoot and rearfoot impacts.
Depression and Anxiety Disorders in Patients With Inflammatory Bowel Disease

Mental health is a significant yet overlooked aspect of inflammatory bowel disease (IBD) patient care, with challenges in determining optimal treatments and psychological health resources. The most common psychological conditions in patients with IBD are anxiety and depression. The increased prevalence of these mental disorders appeals to mental screening of each person diagnosed with IBD at initial consultation. There are simple and clinically viable methods available to screen for mental problems. Psychological methods may be as or even more significant as a therapeutic modality. Herein we discuss the three major areas of psychological co-morbidity in IBD: (1) the prevalence and risk factors associated with anxiety and depression disorders for patients with IBD; (2) diagnosis of psychological disorders for patients with IBD; (3) treatment with patients with IBD and mental disorders. The gastroenterologists are encouraged to screen and treat these patients with IBD and mental disorders, which may improve outcomes.
Associations of Hyperactivity and Inattention Scores with Theta and Beta Oscillatory Dynamics of EEG in Stop-Signal Task in Healthy Children 7–10 Years Old

Simple Summary Most studies on ADHD have been focused on the comparisons between healthy subjects and clinical patients. The dimensional approaches propose that the main pathological behavioral domains are distributed in the normal population and not only in individual categories of people (as assumed in traditional schemes of comparisons between patients and controls). In the current study, we used a similar approach to identify potential markers of ADHD by studying the EEG dynamics of healthy children with a natural variability in hyperactivity and inattention scores during performance of the Stop-Signal task. We found that hyperactivity/inattention scores were positively associated with RT variability. Hyperactivity/inattention scores were negatively associated with an increase in beta spectral power in the first 200 ms and positively associated with an increase in theta rhythm at about 300 ms after presentation of the Go stimulus. It has been hypothesized that such results imply insufficient vigilance in the early stages of perception and subsequent compensatory enhancing of attention to the stimulus in children with higher hyperactivity and inattention scores. Abstract In the current study, we aimed to investigate the associations between the natural variability in hyperactivity and inattention scores, as well as their combination with EEG oscillatory responses in the Stop-Signal task in a sample of healthy children. During performance, the Stop-Signal task EEGs were recorded in 94 Caucasian children (40 girls) from 7 to 10 years. Hyperactivity/inattention and inattention scores positively correlated with RT variability. Hyperactivity/inattention and inattention scores negatively correlated with an increase in beta spectral power in the first 200 ms after presentation of the Go stimulus. Such results are in line with the lack of arousal model in ADHD children and can be associated with less sensory arousal in the early stages of perception in children with symptoms of inattention. The subsequent greater increase in theta rhythm at about 300 ms after presentation of the Go stimulus in children with higher inattention scores may be associated with increased attention processes and compensation for insufficient vigilance in the early stages of perception.
Discovery of a Metabolic Signature Predisposing High Risk Patients with Mild Cognitive Impairment to Converting to Alzheimer’s Disease

Assessing dementia conversion in patients with mild cognitive impairment (MCI) remains challenging owing to pathological heterogeneity. While many MCI patients ultimately proceed to Alzheimer’s disease (AD), a subset of patients remain stable for various times. Our aim was to characterize the plasma metabolites of nineteen MCI patients proceeding to AD (P-MCI) and twenty-nine stable MCI (S-MCI) patients by untargeted metabolomics profiling. Alterations in the plasma metabolites between the P-MCI and S-MCI groups, as well as between the P-MCI and AD groups, were compared over the observation period. With the help of machine learning-based stratification, a 20-metabolite signature panel was identified that was associated with the presence and progression of AD. Furthermore, when the metabolic signature panel was used for classification of the three patient groups, this gave an accuracy of 73.5% using the panel. Moreover, when specifically classifying the P-MCI and S-MCI subjects, a fivefold cross-validation accuracy of 80.3% was obtained using the random forest model. Importantly, indole-3-propionic acid, a bacteria-generated metabolite from tryptophan, was identified as a predictor of AD progression, suggesting a role for gut microbiota in AD pathophysiology. Our study establishes a metabolite panel to assist in the stratification of MCI patients and to predict conversion to AD.
Preclinical and Clinical Antioxidant Effects of Natural Compounds against Oxidative Stress-Induced Epigenetic Instability in Tumor Cells

ROS (reactive oxygen species) are produced via the noncomplete reduction in molecular oxygen in the mitochondria of higher organisms. The produced ROS are placed in various cell compartments, such as the mitochondria, cytoplasm, and endoplasmic reticulum. In general, there is an equilibrium between the synthesis of ROS and their reduction by the natural antioxidant defense system, called the redox system. Therefore, when this balance is upset, the excess ROS production can affect different macromolecules, such as proteins, lipids, nucleic acids, and sugars, which can lead to an electronic imbalance than oxidation of these macromolecules. Recently, it has also been shown that ROS produced at the cellular level can affect different signaling pathways that participate in the stimulation of transcription factors linked to cell proliferation and, consequently, to the carcinogenesis process. Indeed, ROS can activate the pathway of tyrosine kinase, MAP kinase, IKK, NF-KB, phosphoinositol 3 phosphate, and hypoxia-inducible factor (HIF). The activation of these signaling pathways directly contributes to the accelerated proliferation process and, as a result, the appearance of cancer. In addition, the use of antioxidants, especially natural ones, is now a major issue in the approach to cancer prevention. Some natural molecules, especially phytochemicals isolated from medicinal plants, have now shown interesting preclinical and clinical results.
Porphyrias in the Age of Targeted Therapies

The porphyrias are a group of eight rare genetic disorders, each caused by the deficiency of one of the enzymes in the heme biosynthetic pathway, resulting in the excess accumulation of heme precursors and porphyrins. Depending on the tissue site as well as the chemical characteristics of the accumulating substances, the clinical features of different porphyrias vary substantially. Heme precursors are neurotoxic, and their accumulation results in acute hepatic porphyria, while porphyrins are photoactive, and excess amounts cause cutaneous porphyrias, which present with photosensitivity. These disorders are clinically heterogeneous but can result in severe clinical manifestations, long-term complications and a significantly diminished quality of life. Medical management consists mostly of the avoidance of triggering factors and symptomatic treatment. With an improved understanding of the underlying pathophysiology and disease mechanisms, new treatment approaches have become available, which address the underlying defects at a molecular or cellular level, and promise significant improvement, symptom prevention and more effective treatment of acute and chronic disease manifestations.
Risk Allele Frequency Analysis of Single-Nucleotide Polymorphisms for Vitamin D Concentrations in Different Ethnic Group

The prevalence of vitamin D deficiency varies from 20.8% to 61.6% among populations of different ethnicities, suggesting the existence of a genetic component. The purpose of this study was to provide insights into the genetic causes of vitamin D concentration differences among individuals of diverse ancestry. We collected 320 single-nucleotide polymorphisms (SNPs) associated with vitamin D concentrations from a genome-wide association studies catalog. Their population-level allele frequencies were derived based on the 1000 Genomes Project and Korean Reference Genome Database. We used Fisher’s exact tests to assess the significance of the enrichment or depletion of the effect allele at a given SNP in the database. In addition, we calculated the SNP-based genetic risk score (GRS) and performed correlation analysis with vitamin D concentration that included latitude. European, American, and South Asian populations showed similar heatmap patterns, whereas African, East Asian, and Korean populations had distinct ones. The GRS calculated from allele frequencies of vitamin D concentration was highest among Europeans, followed by East Asians and Africans. In addition, the difference in vitamin D concentration was highly correlated with genetic factors rather than latitude effects.
The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice

Previous studies implicated the histamine H4 receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H4 receptor knockout mice (H4R−/−). Healthy and diabetic H4R−/− mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H4R−/− and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H4R−/− mice displayed a higher basal glycemia. H4R−/− mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H4R−/− mice presented a higher expression of megalin and a lower basal expression of the sodium-hydrogen exchanger (NHE)3 and aquaporin (AQP)2. According to these basal differences, diabetic H4R−/− mice developed more severe hyperglycemia and a higher 24 h urine volume, but a lower increase in ACR and decrease in urine pH were observed. These events were paralleled by a reduced NHE3 over-expression and megalin loss in diabetic H4R−/− mice. The AQP1 and AQP7 patterns were also different between H4R−/− and wild-type diabetic mice. The collected results highlight the role of the histamine H4 receptor in the control of renal reabsorption processes, particularly albumin uptake.
Transposable Element Dynamics and Regulation during Zygotic Genome Activation in Mammalian Embryos and Embryonic Stem Cell Model Systems

Transposable elements (TEs) are mobile genetic sequences capable of duplicating and reintegrating at new regions within the genome. A growing body of evidence has demonstrated that these elements play important roles in host genome evolution, despite being traditionally viewed as parasitic elements. To prevent ectopic activation of TE transposition and transcription, they are epigenetically silenced in most somatic tissues. Intriguingly, a specific class of TEs—retrotransposons—is transiently expressed at discrete phases during mammalian development and has been linked to the establishment of totipotency during zygotic genome activation (ZGA). While mechanisms controlling TE regulation in somatic tissues have been extensively studied, the significance underlying the unique transcriptional reactivation of retrotransposons during ZGA is only beginning to be uncovered. In this review, we summarize the expression dynamics of key retrotransposons during ZGA, focusing on findings from in vivo totipotent embryos and in vitro totipotent-like embryonic stem cells (ESCs). We then dissect the functions of retrotransposons and discuss how their transcriptional activities are finetuned during early stages of mammalian development.
Superinfection with Difficult-to-Treat Pathogens Significantly Reduces the Outcome of Periprosthetic Joint Infections

Periprosthetic joint infection (PJI) is a serious complication after total joint arthroplasty. In the course of a PJI, superinfections with pathogens that do not match the primary infecting micro-organism may occur. To our knowledge, there are no published data on the outcome of such infections in the literature. The aim of this study was to assess the outcome of PJI with superinfections with a difficult-to-treat (DTT) pathogen. Data of 169 consecutive patients with PJI were retrospectively analyzed in this single-center study. Cases were categorized into: Group 1 including non-DTT-PJI without superinfection, Group 2 DTT-PJI without superinfection, Group 3 non-DTT-PJI with DTT superinfection, and Group 4 non-DTT-PJI with non-DTT superinfection. Group 3 comprised 24 patients and showed, after a mean follow-up of 13.5 ± 10.8 months, the worst outcome with infection resolution in 17.4% of cases (p = 0.0001), PJI-related mortality of 8.7% (p = 0.0001), mean revision rate of 6 ± 3.6 (p < 0.0001), and duration of antibiotic treatment of 71.2 ± 45.2 days (p = 0.0023). PJI caused initially by a non-DTT pathogen with a superinfection with a DTT pathogen is significantly associated with the worst outcome in comparison to non-DTT-PJI, PJI caused initially by a DTT pathogen, and to non-DTT-PJI with a non-DTT superinfection.
Lipopolysaccharide of the Yersinia pseudotuberculosis Complex

Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the major surface component of the Gram-negative bacterial cell envelope responsible for the activation of the host’s innate immune system. Variations of the LPS structure utilized by Gram-negative bacteria promote survival by providing resistance to components of the innate immune system and preventing recognition by TLR4. This review summarizes studies of the biosynthesis of Yersinia pseudotuberculosis complex LPSs, and the roles of their structural components in molecular mechanisms of yersiniae pathogenesis and immunogenesis.
Copy Neutral LOH Affecting the Entire Chromosome 6 Is a Frequent Mechanism of HLA Class I Alterations in Cancer

Simple Summary Loss of antigen presentation due to the altered expression of tumor HLA class I (HLA-I) molecules is a common mechanism of cancer immune escape. Loss of HLA-I haplotype, locus or a single allele due to genetic and chromosomal aberrations, may result in reduced antigen presentation and, thus, facilitate immune evasion. Here, we demonstrate the prevalence of the copy neutral loss of heterozygosity (CN-LOH) involving HLA-I heavy chain and B2M gene in various human tumor cell lines and tissues. We discuss the impact of the LOH in HLA genes on tumor immune rejection, clonal expansion and association with the cancer recurrence in the immunotherapy settings. It represents a genetic barrier for effective treatment and can be considered as a potential genetic biomarker of cancer immune escape. Abstract Total or partial loss of HLA class I antigens reduce the recognition of specific tumor peptides by cytotoxic T lymphocytes favoring cancer immune escape during natural tumor evolution. These alterations can be caused by genomic defects, such as loss of heterozygosity at chromosomes 6 and 15 (LOH-6 and LOH-15), where HLA class I genes are located. There is growing evidence indicating that LOH in HLA contributes to the immune selection of HLA loss variants and influences the resistance to immunotherapy. Nevertheless, the incidence and the mechanism of this chromosomal aberration involving HLA genes has not been systematically assessed in different types of tumors and often remains underestimated. Here, we used SNP arrays to investigate the incidence and patterns of LOH-6 and LOH-15 in a number of human cancer cell lines and tissues of different histological types. We observed that LOH in HLA is a common event in cancer samples with a prevalence of a copy neutral type of LOH (CN-LOH) that affects entire chromosome 6 or 15 and involves chromosomal duplications. LOH-6 was observed more often and was associated with homozygous HLA genotype and partial HLA loss of expression. We also discuss the immunologic and clinical implications of LOH in HLA on tumor clonal expansion and association with the cancer recurrence after treatment.
Sildenafil-Mediated Neuroprotection from Adult to Neonatal Brain Injury: Evidence, Mechanisms, and Future Translation

Cerebral stroke, traumatic brain injury, and hypoxic ischemic encephalopathy are among the most frequently occurring brain injuries. A complex pathogenesis, characterized by a synergistic interaction between alterations of the cerebrovascular system, cell death, and inflammation, is at the basis of the brain damage that leads to behavioral and neurodevelopmental disabilities in affected subjects. Sildenafil is a selective inhibitor of the enzyme phosphodiesterase 5 (PDE5) that is able to cross the blood–brain barrier. Preclinical data suggest that sildenafil may be a good candidate for the prevention or repair of brain injury in both adults and neonates. The aim of this review is to summarize the evidence supporting the neuroprotective action of sildenafil and discuss the possible benefits of the association of sildenafil with current therapeutic strategies.
The Role of Vitamins in Neurodegenerative Disease: An Update

Acquiring the recommended daily allowance of vitamins is crucial for maintaining homeostatic balance in humans and other animals. A deficiency in or dysregulation of vitamins adversely affects the neuronal metabolism, which may lead to neurodegenerative diseases. In this article, we discuss how novel vitamin-based approaches aid in attenuating abnormal neuronal functioning in neurodegeneration-based brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and Prion disease. Vitamins show their therapeutic activity in Parkinson’s disease by antioxidative and anti-inflammatory activity. In addition, different water- and lipid-soluble vitamins have also prevented amyloid beta and tau pathology. On the other hand, some results also show no correlation between vitamin action and the prevention of neurodegenerative diseases. Some vitamins also exhibit toxic activity too. This review discusses both the beneficial and null effects of vitamin supplementation for neurological disorders. The detailed mechanism of action of both water- and lipid-soluble vitamins is addressed in the manuscript. Hormesis is also an essential factor that is very helpful to determine the effective dose of vitamins. PubMed, Google Scholar, Web of Science, and Scopus were employed to conduct the literature search of original articles, review articles, and meta-analyses.