Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variants of mineral metabolism in health and disease.

PURPOSE OF REVIEW Disturbances in mineral metabolism are common among individuals with chronic kidney disease and have consistently been associated with cardiovascular and bone disease. The current review aims to describe the current knowledge of the genetic aspects of mineral metabolism disturbances and to suggest directions for future studies to uncover the cause and pathogenesis of chronic kidney disease - mineral bone disorder. RECENT FINDINGS The most severe disorders of mineral metabolism are caused by highly penetrant, rare, single-gene disruptive mutations. More recently, genome-wide association studies (GWAS) have made an important contribution to our understanding of the genetic determinants of circulating levels of 25-hydroxyvitamin D, calcium, phosphorus, fibroblast growth factor-23, parathyroid hormone, fetuin-A and osteoprotegerin. Although the majority of these genes are known members of mineral homeostasis pathways, GWAS with larger sample sizes have enabled the discovery of many genes not known to be involved in the regulation of mineral metabolism. SUMMARY GWAS have enabled remarkable developments in our ability to discover the genetic basis of mineral metabolism disturbances. Although we are far from using these findings to inform clinical practice, we are gaining understanding of novel biological mechanisms and providing insight into ethnic variation in these traits.
Regulatory B Cells Normalize CNS Myeloid Cell Content in a Mouse Model of Multiple Sclerosis and Promote Oligodendrogenesis and Remyelination

The unmet medical need of patients with multiple sclerosis (MS) is the inexorable loss of CNS myelin and latterly neurons leading to permanent neurologic disability. Solicitation of endogenous oligodendrocytes progenitor cells, the precursor of oligodendrocytes, to remyelinate axons may abort the onset of disability. In female mice with experimental autoimmune encephalomyelitis (EAE), a murine model of MS, adoptive transfer of IL-10+ regulatory B cells (Bregs) has been shown to reverse EAE by promoting the expansion of peripheral and CNS-infiltrating IL-10+ T cells. Here, we examined whether Bregs treatment and its bystander effect on regulatory T cells are associated with CNS repair as reflected by oligodendrogenesis and remyelination. We have found that transfusion of Bregs reverses established clinical EAE and that clinical improvement is associated with a significant increase in spinal cord remyelination as reflected by g-ratio analysis within the thoracic and lumbar spine. We further observed in the spinal cords of EAE Bregs-treated mice that CNS resident CD11b/CD45intLy6C– microglia, and infiltrating CD11b+/CD45high monocytes/macrophages content reverts to normal and polarize to a M2-like CD206+ phenotype. Concurrently, there was a substantial increase in neo-oligodendrogenesis as manifest by an increase in CD45–/low CNS cells expressing A2B5, an early marker in oligodendrocytes progenitor cell differentiation as well as GalC+/O1+ premyelinating and myelin basic protein+/myelin oligodendrocyte glycoprotein+ mature oligodendrocytes with reciprocal downregulation of paired related homeobox protein 1. These results demonstrate that the clinical benefit of Bregs is associated with normalization of CNS immune milieu and concurrent activation of oligodendrocyte progenitor cells with subsequent remyelination. SIGNIFICANCE STATEMENT In multiple sclerosis patients, demyelination progresses with aging and disease course, leading to irreversible disability. In this study, we have discovered, using a mouse model of multiple sclerosis, that the transfusion of autologous regulatory B cells (Bregs) is able to ameliorate, cure, and sustain the durable remission of the disease. We show that the adoptive transfer of Bregs dramatically decreased the frequency of myeloid-derived cells, both infiltrating monocytes/macrophages and resident microglia, and converted their phenotype to an immunosuppressive-like phenotype. Moreover, we showed that CNS oligodendrocyte progenitor cells are activated following Bregs treatment and differentiate into myelinating oligodendrocytes, which results in neo-oligodendrogenesis and remyelination of spinal cords.
Gaze-behaviors of runners in a natural, urban running environment

Gaze-tracking techniques have advanced our understanding of visual attention and decision making during walking and athletic events, but little is known about how vision influences behavior during running over common, natural obstacles. This study tested hypotheses about whether runners regularly collect visual information and pre-plan obstacle clearance (feedforward control), make improvisational adjustments (online control), or some combination of both. In this study, the gaze profiles of 5 male and 5 female runners, fitted with a telemetric gaze-tracking device, were used to identify the frequency of fixations on an obstacle during a run. Overall, participants fixated on the obstacle 2.4 times during the run, with the last fixation occurring on average between 40% and 80% of the run, suggesting runners potentially shifted from a feedforward planning strategy to an online control strategy during the late portions of the running trial. A negative association was observed between runner velocity and average number of fixations. Consistent with previous studies on visual strategies used during walking, our results indicate that visual attentiveness is part of an important feedforward strategy for runners allowing them to safely approach an obstacle. Thus, visual obstacle attention is a key factor in the navigation of complex, natural landscapes while running.
Using social marketing concepts to promote the integration of systematic conservation plans in land-use planning in South Africa

Abstract Local land-use planning procedures are increasingly recognized as potentially crucial to ensure off-reserve biodiversity protection. Mainstreaming systematic conservation planning maps in these decision-making procedures has been proposed as a mechanism to achieve this. However, research is lacking on how to convince officials and politicians to change their behaviour and include the maps in their decision-making. Social marketing is a tool commonly used to effect behaviour change in many sectors but its application in conservation is limited. In the formative research phase of a social marketing study we interviewed locally elected politicians in four coastal municipalities in South Africa. We found that conservation and environmental issues play virtually no role in their work; however, they do attribute value to the natural environment. Land-use planning procedures are considered important but dysfunctional and the role of conservation is perceived negatively in their municipalities. Their information-seeking behaviour is clearly localized. We present a marketing analysis of these results and argue for improving the attractiveness of the product: the maps should be more option- than veto-based and should identify locally relevant ecosystem services. Locally significant information should be provided at a time and location convenient for politicians. We conclude that engagement with councillors should be proactive, refer to land-use planning and services from ‘nature’ rather than ‘biodiversity’ and use terminology and information that is locally oriented and meaningful from the politician's perspective. The analysis highlights the usefulness of the marketing approach for conservation.
Metagenomic Analysis of the Gut Microbiome Reveals Enrichment of Menaquinones (Vitamin K2) Pathway in Diabetes Mellitus

Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with a high prevalence worldwide, especially among overweight and obese populations. T2DM is multifactorial with several genetic and acquired risk factors that lead to insulin resistance. Mounting evidence indicates that alteration of gut microbiome composition contribute to insulin resistance and inflammation. However, the precise link between T2DM and gut microbiome role and composition remains unknown. Methods We evaluated the metabolic capabilities of the gut microbiome of twelve T2DM and six healthy individuals through shotgun metagenomics using MiSeq platform. Results We identified no significant differences in the overall taxonomic composition between healthy and T2DM subjects when controlling for differences in diet. However, results showed that T2DM enriched in metabolic pathways involved in menaquinone (vitamin K2) superpathway biosynthesis (PWY-5838) as compared to healthy individuals. Covariance analysis between the bacterial genera and metabolic pathways displaying difference in abundance (analysis of variance P<0.05) in T2DM as compared to healthy subjects revealed that genera belonging Firmicutes, Actinobacteria, and Bacteroidetes phyla contribute significantly to vitamin K2 biosynthesis. Further, the microbiome corresponding to T2DM with high glycosylated hemoglobin (HbA1c) (>6.5%) exhibit high abundance of genes involved in lysine biosynthesis and low abundance of genes involved in creatinine degradation as compared to T2DM with lower HbA1c (<6.5%). Conclusion The identified differences in metabolic capabilities provide important information that may eventually lead to the development of novel biomarkers and more effective management strategies to treat T2DM.
Quantitative trait loci for flowering, plant and ear height, and kernel traits in maize

The inheritance of quantitative traits is not well understood. A study was conducted to determine the number and chromosomal locations of quantitative trait loci (QTL) controlling male anthesis date ; plant and ear height ; kernel weight ; and kernel protein, oil, and starch concentration in maize (Zea mays L.). Two hundred S 1 lines were derived from a single F 1 plant from a cross of Illinois High Oil (IHO) by Illinois Low Oil (Early Maturity) [ILO(EM)]. Restriction fragment length polymorphism (RFLP) analysis was performed to determine RFLP genotypes of the 200 S 1 families at 80 polymorphic loci spaced on average 24 centimorgans throughout the genome. The 200 S 1 families were measured for phenotypic traits in replicated field trials during 1992 and 1993. Analysis of variance detected significant (P < 0.05) associations between several RFLP loci and each phenotypic trait. A total of 16 marker loci clustered in eight chromosomal regions were significantly associated with male anthesis date, 18 marker loci clustered in 11 regions were significantly associated with plant height, 14 marker loci clustered in nine regions were significantly associated with ear height, 27 marker loci clustered in 11 regions were associated with kernel weight, 16 marker loci clustered in eight regions were associated with protein concentration, 31 marker loci clustered in 11 regions were associated with oil concentration, and 28 marker loci clustered in 13 regions were associated with starch concentration. A number of QTL were detected in chromosomal regions where known gene loci of biological relevance are located.
Nesfatin-1 alleviates acute lung injury through reducing inflammation and oxidative stress via the regulation of HMGB1.

OBJECTIVE Acute lung injury (ALI) is the most common complication of sepsis, with rapid onset and high mortality. There is currently no effective treatment for ALI. Therefore, we looked for a good method of treating ALI by studying the effect and mechanism of Nesfatin-1 on ALI. MATERIALS AND METHODS We used LPS to induce mouse and human alveolar epithelial cell line BEAS-2B to construct an ALI model. Recombinant Nesfatin-1 was administered subcutaneously to mice or used to stimulate BEAS-2B cells. We collected mouse bronchoalveolar lavage fluid and mouse lung tissue to detect changes in inflammatory factors and oxidative stress levels. In addition, we examined the expression changes of HMGB1 to study the mechanism of Nesfatin-1. RESULTS Exogenous Nesfatin-1 significantly attenuated LPS-induced ALI and reduced inflammation levels and oxidative stress levels in mouse lung tissue. In cell experiments, Nesfatin-1 also reduced inflammation levels and oxidative stress levels in BEAS-2B cells. In addition, Nesfatin-1 reduced the expression of HMGB1 in mouse lung tissues and BEAS-2B cells, and decreased the activity of p38MAPK and NF-κB signaling pathways in the inflammation-related pathway downstream of HMGB1. However, after overexpression of HMGB1, the therapeutic effect of Nesfatin-1 on ALI was attenuated. CONCLUSIONS Nesfatin-1 regulates the expression of HMGB1 in alveolar epithelial cells. By reducing the expression of HMGB1, Nesfatin-1 can reduce the inflammation-related signaling pathway downstream of HMGB1 to reduce the level of inflammation and oxidative stress in alveolar epithelial cells, thereby alleviating ALI.
Community Group Model Building as a Method for Engaging Participants and Mobilising Action in Public Health

Group model building (GMB) is a qualitative method aimed at engaging stakeholders to collectively consider the causes of complex problems. Tackling inequities in community nutrition is one such complex problem, as the causes are driven by a variety of interactions between individual factors, social structures, local environments and the global food system. This methods paper describes a GMB process that utilises three system mapping tools in a study with members of a multicultural, low-income community to explore declining fruit and vegetable intake in children. The tools were: (1) graphs over time, which captures the community’s understanding of an issue; (2) cognitive mapping, which enables participants to think systemically about the causes and consequences of the issue; (3) causal loop diagrams, which describe feedback loops that reinforce the issue and identify potential actions. Cognitive mapping, a tool not usually associated with GMB, was added to the research process to support the gradual development of participants’ thinking and develops the skills needed to tackle an issue from a systems perspective. We evaluate the benefits and impact of these three tools, particularly in engaging participants and increasing understanding of systems thinking in order to develop and mobilise action. The tools could be adapted for use in other community-based research projects. Key learnings were the value of genuine partnership with a local organisation for longevity of the project, recruitment of key decisionmakers from the community early in the process, and allowing time to create sustainable change.
Long-term Autograft Harvest Site Pain After Ankle and Hindfoot Arthrodesis

Background: Pain following autograft harvest has been studied; however, published literature has typically focused on the iliac crest with follow-up limited to only a few years. It remains unknown if pain continues or improves over time. The purpose of this study was to evaluate long-term pain associated with autograft harvest to supplement hindfoot or ankle arthrodesis. Methods: Subjects in the control arm of a previously conducted trial comparing autograft with a synthetic bone graft for hindfoot or ankle arthrodesis were invited back for a single visit at a minimum of 5 years following their initial surgery. Harvest site, fusion site, and weight-bearing pain were evaluated using a 100-point visual analog scale (VAS). Of the 130 invited subjects, 60 (46.1%) returned for assessment, 58 of whom completed pain assessments. Results: At a mean follow-up of 9.0 years (range, 7.8-10.5), more than a third (36.6%) of subjects had some level of harvest site pain. Using VAS greater than 20 mm as a threshold of clinical significance, pain remained clinically significant in 5.2% of subjects. There was a significant correlation between harvest site pain and both weight-bearing and fusion site pain. There was not a significant correlation between harvest site pain and volume of graft harvested. Conclusion: Autograft harvest can result in chronic, clinically significant pain that can last up to 10 years. In the era of shared decision making, this information will help surgeons and patients quantify the risks of chronic pain after arthrodesis procedures that include a secondary operative incision for graft harvest. Level of Evidence: Level II, prospective comparative study.
Vitamin D status is seasonally stable in northern European dogs.

BACKGROUND Numerous studies in veterinary species have recently linked vitamin D status with nonskeletal health disorders. Previous studies have indicated that dogs cannot produce endogenous vitamin D via cutaneous production and rely solely on dietary intake of vitamin D. The seasonal variation of vitamin D seen in humans due to changes in ultraviolet (UV) exposure, therefore, is unlikely to be replicated in these animals. OBJECTIVES The objective of this study was to investigate the natural variation in 25-hydroxyvitamin-D concentrations in dogs subject to seasonal UV exposure. METHODS This longitudinal study followed 18 healthy dogs fed a standardized diet over 1 year, with blood samples obtained monthly. Two key vitamin D metabolites, 25-hydroxyvitamin-D2 and 25-hydroxyvitamin-D3 , were assessed by liquid chromatography-tandem mass spectrometry in serum samples. Various other biochemical parameters were also measured. Seasonality was assessed using cosinor statistical analysis. RESULTS Although the dogs were subject to seasonally varying UV radiation, 25-hydroxyvitamin-D and related biomarkers (including calcium and parathyroid hormone) remained stable over time and did not follow a seasonal pattern. 25-hydroxyvitamin-D was not positively correlated with exposure to UV radiation. Nonetheless, variation in 25-hydroxyvitamin-D concentrations between individual dogs was detected. CONCLUSIONS Given the standardization of diet, we concluded that the seasonal stability of 25-hydroxyvitamin-D concentration (vitamin D status) was likely a direct result of lack of cutaneous vitamin D production in this species and highlights the importance of dietary intake. The variation in 25-hydroxyvitamin-D concentration between animals warrants further investigation.
Analysis of epidemics of northern leaf blight on sweet corn in Israel

Apparent infection rate (r) in the field varied from 0.05 to 0.20/day. There was a low correlation between temperatures and dew periods favorable for disease development and r in the field. A significant and high correlation was found between r and components of fitness measured in the growth chambers. A simple northern leaf blight simulator used to examine the influence of fitness of the pathogen on development of disease indicated that the importance of weather conditions decreases when fields are infected with a highly aggressive population of the pathogen
A novel thrombopoietin (THPO) mutation altering mRNA splicing in a case of familial thrombocytosis

G. Auerswald, Bremen, Germany, C. Barnes, Melbourne, Australia, E. Chalmers, Glasgow, UK, H. Chambost, Marseille, France, N. Clausen, Aarhus, Denmark, A.L. Dunn, Columbus, OH, USA, C. Escuriola Ettinghausen, Frankfurt, Germany, K. Fischer, Utrecht, The Netherlands, K. Fijnvandraat, Amsterdam, The Netherlands, C. van Geet, Leuven, Belgium, M. Hoffmann, Copenhagen, Denmark, K. Kavakli, Izmir, Turkey, G. Kenet, Tel Aviv, Israel, C. K€ onigs, Frankfurt, Germany, K. Kurnik, Munich, Germany, M. MancoJohnson, Denver, CO, USA, M.E. Mancuso, Milan, Italy, C. Molinari, Genua, Italy, W. Muntean, Graz, Switzerland, B. Nolan, Dublin, Ireland, R. Perez Garrido, Valencia, Spain, E. Platokouki, Athens, Greece, A. Rafowicz, Paris, France, E. Santagostino, Milan, Italy, A. Shapiro, Indianapolis, IN, USA, A. Thomas, Edinburgh, UK, M. Williams, Birmingham, UK.
Epigenetic Regulation of Alternative mRNA Splicing in Dilated Cardiomyopathy

In recent years, the genetic architecture of dilated cardiomyopathy (DCM) has been more thoroughly elucidated. However, there is still insufficient knowledge on the modifiers and regulatory principles that lead to the failure of myocardial function. The current study investigates the association of epigenome-wide DNA methylation and alternative splicing, both of which are important regulatory principles in DCM. We analyzed screening and replication cohorts of cases and controls and identified distinct transcriptomic patterns in the myocardium that differ significantly, and we identified a strong association of intronic DNA methylation and flanking exons usage (p < 2 × 10−16). By combining differential exon usage (DEU) and differential methylation regions (DMR), we found a significant change of regulation in important sarcomeric and other DCM-associated pathways. Interestingly, inverse regulation of Titin antisense non-coding RNA transcript splicing and DNA methylation of a locus reciprocal to TTN substantiate these findings and indicate an additional role for non-protein-coding transcripts. In summary, this study highlights for the first time the close interrelationship between genetic imprinting by DNA methylation and the transport of this epigenetic information towards the dynamic mRNA splicing landscape. This expands our knowledge of the genome–environment interaction in DCM besides simple gene expression regulation.
On the Effect of Discussions on Pull Request Decisions

—Open-source software relies on contributions from different types of contributors. Online collaborative development platforms, such as GitHub, usually provide explicit support for these contributions through the mechanism of pull requests, allowing project members and external contributors to discuss and evaluate the submitted code. These discussions can play an important role in the decision-making process leading to the acceptance or rejection of a pull request. We empirically examine in this paper 183K pull requests and their discussions, for almost 4.8K GitHub repositories for the Cargo ecosystem. We investigate the prevalence of such discussions, their participants and their size in terms of messages and durations, and study how these aspects relate to pull request decisions.