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Introduction: Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This work requires a comprehensive catalogue of commonly observed genetic variations in the mitochondrial DNAs for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied. Objectives: To address this shortcoming, we have created the most comprehensive quality-controlled North and East African mitochondrial data set to date and use it for characterizing mitochondrial genetic variation in this region. Methods: We compiled 11 published cohorts with novel data for mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n = 2504) and the Human Genome Diversity Project (n = 828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination, as well as Nanopore long read sequencing for haplogroup validation of 18 samples. Results: Using a subset of high-coverage mitochondrial sequences, we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1. Conclusion: Our findings demonstrate common hitherto unexplored variants in mitochondrial genomes of North and East Africa that lead to novel phylogenetic relationships between haplogroups present in these regions. These observations call for further in-depth population genetic studies in that region to enable the prospective use of mitochondrial genetic variation for precision medicine.

Abstract Diabetes mellitus (DM) represents a major health problem in Egypt and worldwide, with increasing numbers of patients with prediabetes every year. Numerous factors, such as obesity, hyperlipidemia, and hypertension, which have recently become serious concerns, affect the complex pathophysiology of diabetes. These metabolic syndrome diseases are highly linked to genetic variability that drives certain populations, such as Egypt, to be more susceptible to developing DM. Here we conduct a comprehensive analysis to pinpoint the similarities and uniqueness among the Egyptian genome reference and the 1000-genome subpopulations (Europeans, Ad-Mixed Americans, South Asians, East Asians, and Africans), aiming at defining the potential genetic risk of metabolic syndromes. Selected approaches incorporated the analysis of the allele frequency of the different populations’ variations, supported by genotypes’ principal component analysis. Results show that the Egyptian’s reference metabolic genes were clustered together with the Europeans’, Ad-Mixed Americans’, and South-Asians’. Additionally, 8563 variants were uniquely identified in the Egyptian cohort, from those, two were predicted to cause structural damage, namely, CDKAL1: 6_21065070 (A > T) and PPARG: 3_12351660 (C > T) utilizing the Missense3D database. The former is a protein coding gene associated with Type 2 DM while the latter is a key regulator of adipocyte differentiation and glucose homeostasis. Both variants were detected heterozygous in two different Egyptian individuals from overall 110 sample. This analysis sheds light on the unique genetic traits of the Egyptian population that play a role in the DM high prevalence in Egypt. The proposed analysis pipeline -available through GitHub- could be used to conduct similar analysis for other diseases across populations.

Abstract Background Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota. Results Staphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and microbial composition in the gut and skin. Conclusions Dysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota. Video Abstract

Chemistry laboratories ordinarily involve a number of visual observations and require qualitative and quantitative explanations of these observations. A student with blindness at Truman State University successfully completed the laboratory portion of the non-majors liberal arts chemistry course with the assistance of a senior undergraduate chemistry education major, the guidance of a chemistry professor with blindness, and a variety of alternative laboratory methods. Volumes were measured using a notched syringe or the graduated cylinder pipet technique. Changes in color were measured by a Color Analysis Laboratory Sensor (CALS) and a Submersible Audio Light Sensor (SALS). Balance and Vernier probe measurements were recorded using Vernier data acquisition software (Logger Pro 3.6) and Job Access with Speech (JAWS) screen review software. This paper reports the impact of these alternative methods on the level of participation of the student with blindness for the following experiments: Density Determination, Flame Emissions Tests, Simulation of the Measurement of Hemoglobin in the Blood Using Spectrophotometry, the Investigation of Hydrates, the Study of Chemical Reactions in Everyday Life, and Titrations. The Solutions, the Soap-Making, and Paper Chromatography laboratories are not reported. All the laboratories except the Density laboratory are part of the Chemistry 100 curriculum at Truman State University ("CHEM 100", 2010).

The effect of climate change on rockfalls in the German low mountain regions is investigated following two different approaches. The first approach uses a logistic regression model that describes the combined effect of precipitation, freeze–thaw cycles, and fissure water on rockfall probability. The climate change signal for the past 6 decades is analysed by applying the model to meteorological observations. The possible effect of climate change until the end of the century is explored by applying the statistical model to the output of a multi-model ensemble of 23 regional climate scenario simulations. It is found that the number of days per year exhibiting an above-average probability for rockfalls has mostly been decreasing during the last few decades. Statistical significance is, however, present at only a few sites. A robust and statistically significant decrease can be seen in the Representative Concentration Pathway (RCP) climate scenario 8.5 (RCP8.5) simulations for Germany and neighbouring regions, locally falling below −10 % when comparing the last 30 years of the 20th century to the last 30 years of the 21st century. The most important factor determining the projected decrease in rockfall probability is a reduction in the number of freeze–thaw cycles expected under future climate conditions. For the second approach four large-scale meteorological patterns that are associated with enhanced rockfall probability are identified from reanalysis data. The frequency of all four patterns exhibits a seasonal cycle that maximises in the cold half of the year (winter and spring). Trends in the number of days that can be assigned to these patterns are determined both in meteorological reanalysis data and in climate simulations. In the reanalysis no statistically significant trend is found. For the future scenario simulations all climate models show a statistically significant decrease in the number of rockfall-promoting weather situations.

We overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads. To assess WRIC validity seven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events. Sixteen participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose in a crossover design. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and carbohydrate oxidation. Postprandial carbohydrate oxidation trajectories for each participant and condition were modeled using Bayesian Hierarchical Modeling. Mean total error in infusions were 1.27 ± 0.67% and 0.42 ± 0.70% for VO2 and VCO2 respectively, indicating a high level of validity. Mean resting MR was similar across conditions ([Formula: see text] = 1.05 ± 0.03 kcal/min, p = 0.82, ICC: 0.91). While MR increased similarly among all conditions (~13%, p = 0.29), postprandial carbohydrate oxidation parameters were significantly lower for dextrose compared with sucrose or fructose. We provide evidence validating our WRIC and a novel application of statistical methods useful for research using WRIC.

While the Clean Air Act has done a substantial amount for the environment and the health of individuals in the United States, there is still much to be done. For [...]

Gorham-Stout disease (GSD) also known as vanishing bone disease is an idiopathic and rare condition characterized by gross and progressive bone loss along with excessive growth of vascular and lymphatic tissue. Very little is known about the pathogenesis of GSD, which makes the diagnosis challenging and often diagnosed by elimination. We report a case of GSD in a 41-year-old male patient. He presented with bone pain and initial imaging showed widespread osteolytic lesions in the cervical and mid thoracic spine, ribs, sternum, clavicles, scapula, and humerus. Two percutaneous bone biopsies were performed, followed by an open spine biopsy of the lumber 2 spinous process for histological examination. Unfortunately, no diagnosis was reached. Although, he was treated symptomatically, he kept enduring pain and presented again after 7 months. His laboratory values were out of the normal range which prompted thorough investigations. New imaging and bone biopsy revealed multiple osteolytic lesions and vascular lesion with cavernous morphology respectively. GSD was diagnosed after ruling out a neoplastic process and confirming the cavernous morphology with immunohistochemical stain. He was treated symptomatically with immunomodulators, bisphosphonates, and supplements. Patient was counseled to see the specialist regularly. This case will help to increase familiarity and shed insights in the diagnosis of GSD.

(1) Background: Mothers of very preterm (VPT) infants may experience psychological symptoms compromising long-term emotional wellbeing. This study describes the emotional wellbeing of mothers of five-year-old children born VPT. We assess the association between sociodemographic, perinatal and neonatal characteristics, and the child’s health and development at five years old and maternal emotional wellbeing. (2) Methods: Data are from the prospective European “Effective Perinatal Intensive Care in Europe” (EPICE) and subsequent “Screening for Health In very Preterm infantS in Europe” (SHIPS) projects including births

RESUMO Alimentação adequada durante os primeiros anos de vida é fundamental para a saúde e tem repercussões em todos os ciclos da vida do indivíduo. Diversos trabalhos científicos associam efeitos nocivos à saúde com exposição aos agrotóxicos. Foram avaliados 312 agrotóxicos em alimentos comumente presentes na dieta infantil, selecionados a partir do cardápio do programa de alimentação escolar da educação infantil do município do Rio de Janeiro. A seleção dos alimentos baseou-se na frequência de consumo conforme os cardápios semanais da rede municipal de ensino. A análise multirresíduos por Cromatografia Líquida de Ultra Eficiência acoplada à Espectrometria de Massas sequencial em 145 amostras (leite, cereais infantis, banana, maçã, mamão, laranja, feijão e arroz) identificou 426 detecções de 53 agrotóxicos diferentes. Mais de 68% das amostras apresentaram múltiplos resíduos de agrotóxicos. Com os resultados, foi estimada a exposição da população infantil aos resíduos encontrados, indicando potencial risco à saúde das crianças, que precisa ser uma preocupação prioritária da saúde pública. É necessário verificar os impactos toxicológicos do uso de agrotóxicos sobre a saúde infantil, ampliar a aquisição de alimentos orgânicos pelo Programa Nacional de Alimentação Escolar e fortalecer a agroecologia com incentivos e políticas pública, buscando proteção e promoção da saúde coletiva.

To investigate the importance of cow-individual effects and the importance of horn status (horned vs. disbudded), of diet (hay with and without concentrates), and of ambient temperature (10 °C vs. 25 °C) on delayed luminescence (DL) parameters of milk samples, fluorescence excitation spectroscopic (FES) measurements were performed on a total of n = 152 milk samples from 20 cows of a cross-over experiment. Cow-individual variation was investigated in relation to the horn status, diet effects were evaluated by cow in relation to sampling effects, and regression analysis was used to evaluate the importance of the experimental factors on the variation of emission parameters. Variation of short-term emission after yellow excitation (530 to 800 nm) was predominantly related to the individual cow (disbudded cows tended to higher values), and was partly affected by feeding, with higher emission for concentrate-added diets. Short-term emission after white excitation (260 to 850 nm) was most related to ambient temperature, with higher values at warm temperature. Higher emission was observed also in aged (stored) samples or after delayed cooling. The emission after yellow showed to be more robust to handling and ageing of the milk than the emission after white; possible relations to digestive processes of the cow (including the microbiome) are warranted.

Although inclusion is a fundamental tenet of physical literacy (PL), its applicability and inclusivity related to individuals experiencing disability has been assumed but is not well understood. The purpose of this article is to gain a better understanding of the literature pertaining to the inclusiveness of PL for individuals experiencing disability. Following the analysis of 24 pieces of literature published between January 2001 and May 2019, the main findings include: Overall, PL for individuals experiencing disability has been primarily discussed through a lens of ableism, using a narrow perspective, and at a superficial level, though recent discussions have become increasingly representative of contemporary perspectives on disability. Although encouraging, the collective findings reveal an ongoing need to address current assumptions surrounding disability in order to establish meaningful physical activity experiences that are of value to individuals with diverse capabilities, and to create inclusive PL programming that is welcoming and affirming for all.

Summary 5‐Ketofructose (5‐KF) is a promising low‐calorie natural sweetener with the potential to reduce health problems caused by excessive sugar consumption. It is formed by periplasmic oxidation of fructose by fructose dehydrogenase (Fdh) of Gluconobacter japonicus, a membrane‐bound three‐subunit enzyme containing FAD and three haemes c as prosthetic groups. This study aimed at establishing Pseudomonas putida KT2440 as a new cell factory for 5‐KF production, as this host offers a number of advantages compared with the established host Gluconobacter oxydans. Genomic expression of the fdhSCL genes from G. japonicus enabled synthesis of functional Fdh in P. putida and successful oxidation of fructose to 5‐KF. In a batch fermentation, 129 g l−1 5‐KF were formed from 150 g l−1 fructose within 23 h, corresponding to a space‐time yield of 5.6 g l−1 h−1. Besides fructose, also sucrose could be used as substrate for 5‐KF production by plasmid‐based expression of the invertase gene inv1417 from G. japonicus. In a bioreactor cultivation with pulsed sucrose feeding, 144 g 5‐KF were produced from 358 g sucrose within 48 h. These results demonstrate that P. putida is an attractive host for 5‐KF production.

Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype.Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort.Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration.Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment.

Glomerulonephritis (GN) is a complex disease with intricate underlying pathogenic mechanisms. The possible role of underlying complement dysregulation is not fully elucidated in some GN subsets, especially in the setting of autoimmunity or infection. In the current study, diagnosed cases of lupus nephritis (LN) and post-infectious GN (PIGN) were recruited for molecular genetic analysis and targeted next-generation DNA sequencing was performed for two main complement regulating genes: in the fluid phase; CFH, and on tissue surfaces; MCP. Three heterozygous pathogenic variants in CFH (Q172*, W701*, and W1096*) and one likely pathogenic heterozygous variant in MCP (C223R) have been identified in four of the studied LN cases. Additionally, among the several detected variants of uncertain significance, one novel variant (CFH:F614S) was identified in 74% of the studied LN cases and in 65% of the studied PIGN cases. This variant was detected for the first time in the Egyptian population. These findings suggest that subtle mutations may be present in complement regulating genes in patients with immune-complex mediated category of GN that may add to the disease pathogenesis. These findings also call for further studies to delineate the impact of these gene variants on the protein function, the disease course, and outcome.