Miracle-dz/UniFAR-FTUs huggingface dataset:
Mannan Oligosaccharide Suppresses Lipid Accumulation and Appetite in Western Diet-Induced Obese Mice Via Reshaping Gut Microbiome and Enhancing Short-Chain Fatty Acids Production.

SCOPE Obesity is associated with gut microbiome dysbiosis. Mannose oligosaccharide (MOS) has been reported to be a potential prebiotic. The present study was aimed to determine the effects of MOS on Western diet-induced obesity and to uncover the mediating roles of the gut microbiota and microbial metabolites. METHODS AND RESULTS Three-month-old male ICR mice were fed with a high-fat and high-fructose diet for eight weeks. The diet-induced obese mice were then orally administrated with MOS (100 mg/kg/day and 200 mg/kg/day) for four weeks. MOS significantly reduced bodyweight gain, insulin resistance, fatty liver, and inflammatory responses in obese mice. MOS also stimulated lipolysis and inhibited lipogenesis in the adipose tissues. Moreover, MOS restructured the gut microbiome by enhancing the abundance of Bifidobacterium and Lactobacillus in obese mice. The microbial metabolites short-chain fatty acids (SCFAs) were also increased in the feces and serum. Correlation analysis indicated that the appetite suppression and lipid-lowering effects of MOS were highly correlated with the butyrate levels. CONCLUSION MOS suppressed the appetite, which resulted in less lipid deposition. The lower appetite was likely due to an altered gut microbiome and elevated SCFAs production. MOS might be a potential nutraceutical used in bodyweight management and gut health improvement. This article is protected by copyright. All rights reserved.
Moringin Pretreatment Inhibits the Expression of Genes Involved in Mitophagy in the Stem Cell of the Human Periodontal Ligament

Moringin [4-(α-L-rhamnosyloxy) benzyl isothiocyanate] is an isothiocyanate extracted from Moringa oleifera seeds. It is an antioxidant known for several biological properties useful in the treatment of neurodegenerative diseases. Several neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases are linked to dysfunctional mitochondria due to the resulting increase of Reactive Oxygen Species (ROS). Stem cell-based therapeutic treatments in neurodegenerative diseases provide an alternative strategy aimed to replace the impaired tissue. In this study were investigated the deregulated genes involved in mitophagy in the human periodontal ligament stem cells pretreated with moringin. The RNA-seq study reveals the downregulation of PINK1, with a fold change (FC) of −0.56, such as the genes involved in the phagophore formation (MAP1LC3B FC: −0.73, GABARAP FC: −0.52, GABARAPL1 FC: −0.70, GABARAPL2 FC: −0.39). The moringin pretreatment downregulates the pro−apoptotic gene BAX (−0.66) and upregulates the anti-apoptotic genes BCL2L12 (FC: 1.35) and MCL1 (FC: 0.36). The downregulation of the most of the caspases (CASP1 FC: −1.43, CASP4 FC: −0.18, CASP6 FC: −1.34, CASP7 FC: −0.46, CASP8 FC: −0.65) implies the inactivation of the apoptotic process. Our results suggest that mitochondrial dysfunctions induced by oxidative stress can be inhibited by moringin pretreatment in human periodontal ligament stem cells (hPDLSCs).
The Effects of Varying Glenohumeral Joint Angle on Acute Volume Load, Muscle Activation, Swelling, and Echo-Intensity on the Biceps Brachii in Resistance-Trained Individuals

There is a paucity of data on how manipulating joint angles during isolation exercises may impact overall session muscle activation and volume load in resistance-trained individuals. We investigated the acute effects of varying glenohumeral joint angle on the biceps brachii with a crossover repeated measure design with three different biceps curls. One session served as the positive control (CON), which subjects performed 9 sets of bicep curls with their shoulder in a neutral position. The experimental condition (VAR), varied the glenohumeral joint angle by performing 3 sets in shoulder extension (30°), 3 sets neutral (0°), and 3 sets in flexion (90°). Volume load and muscle activation (EMG) were recorded during the training sessions. Muscle swelling and strain were assessed via muscle thickness and echo-intensity responses at pre, post, 24 h, 48 h, and 72 h. There were no significant differences between conditions for most dependent variables. However, the overall session EMG amplitude was significantly higher (p = 0.0001) in VAR compared to CON condition (95%-CI: 8.4% to 23.3%). Our findings suggest that varying joint angles during resistance training (RT) may enhance total muscle activation without negatively affecting volume load within a training session in resistance-trained individuals.
Functional status and life satisfaction of patients with stable angina pectoris in Austria

Objectives Although substantial progress in the treatment of stable angina pectoris (sAP) has been made, little is known about the functional status and quality of life (QoL) of patients in different healthcare systems. Design and methods We undertook a survey using the Seattle Angina Questionnaire (SAQ) (five domains scored form 0—worst assessment to 100—best assessment) to assess symptoms, QoL (including limitation of activities), demographics, geographic distribution and individual disease data in patients with stable coronary artery disease in Austrian cardiology practices. Results A total of 660 patients with sAP with a mean age of 69.2 years were included. SAQ scores were 67.5±24.4 for physical limitation, 65.5±26.6 for angina stability, 79.3±23.2 for angina frequency, 86.3±16.2 for treatment satisfaction and 63.7±24.2 for overall QoL. Multiple regression identified male gender, but also female gender, Eastern Austrian residence and high body mass index as predictive factors for SAQ scoring. A total of 35.6% of the patients reported at least one desirable activity that was limited through AP symptoms. Conclusions Activity and QoL assessments are in accordance with published literature: The number and the diversity of desired activities indicate the need to focus on patient’s individual activity level to improve symptom management.
MitoRACE: evaluating mitochondrial function in vivo and in single cells with subcellular resolution using multiphoton NADH autofluorescence

We developed a novel metabolic imaging approach that provides direct measures of the rate of mitochondrial energy conversion with single‐cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). Measures of mitochondrial NADH flux by mitoRACE are sensitive to physiological and pharmacological perturbations in vivo. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells with potential for broad applications in the study of energy metabolism.
Robust Control in Human Reaching Movements: A Model-Free Strategy to Compensate for Unpredictable Disturbances

Current models of motor learning suggest that multiple timescales support adaptation to changes in visual or mechanical properties of the environment. These models capture patterns of learning and memory across a broad range of tasks, yet do not consider the possibility that rapid changes in behavior may occur without adaptation. Such changes in behavior may be desirable when facing transient disturbances, or when unpredictable changes in visual or mechanical properties of the task make it difficult to form an accurate model of the perturbation. Whether humans can modulate control strategies without an accurate model of the perturbation remains unknown. Here we frame this question in the context of robust control (H∞-control), a control strategy that specifically considers unpredictable disturbances by increasing initial movement speed and feedback gains. Correspondingly, we demonstrate in two human reaching experiments including males and females that the occurrence of a single unpredictable disturbance led to an increase in movement speed and in the gain of rapid feedback responses to mechanical disturbances on subsequent movements. This strategy reduced perturbation-related motion regardless of the direction of the perturbation. Furthermore, we found that changes in the control strategy were associated with co-contraction, which amplified the gain of muscle responses to both lengthening and shortening perturbations. These results have important implications for studies on motor adaptation because they highlight that trial-by-trial changes in limb motion also reflected changes in control strategies dissociable from error-based adaptation. SIGNIFICANCE STATEMENT Humans and animals use internal representations of movement dynamics to anticipate the impact of predictable disturbances. However, we are often confronted with transient or unpredictable disturbances, and it remains unknown whether and how the nervous system handles these disturbances over fast time scales. Here we hypothesized that humans can modulate their control strategy to make reaching movements less sensitive to perturbations. We tested this hypothesis in the framework of robust control, and found changes in movement speed and feedback gains consistent with the model predictions. These changes impacted participants' behavior on a trial-by-trial basis. We conclude that compensation for disturbances over fast time scales involves a robust control strategy, which potentially plays a key role in motor planning and execution.
Advances in aeroallergen immunotherapy.

PURPOSE OF REVIEW Allergic rhinoconjunctivitis is the most common manifestation of allergic disease. This break in the normal natural function of the immune system to ignore harmless molecules such as pollen and pet dander to now aggressively react has lead to a substantial disease burden that is not always recognized and adequately treated. RECENT FINDINGS Individual molecular component testing may increase the predictive value of blood sIgE and clinical symptoms. Defining the most symptoms inducing allergenic protein has led to advances in peptide-based allergen immunotherapy. There have been steady consistent reports that allergy immunotherapy for children with symptomatic allergic rhinitis prevents the onset of asthma. SUMMARY Allergy immunotherapy is an effective disease-modulating treatment that alters the underlying immune dysfunction which is a currently underutilized therapy especially as it is likely effective in preventing the onset of asthma in children, at least in the short term.
MicroRNA biomarkers associated with type 1 myocardial infarction in HIV positive individuals.

OBJECTIVE Individuals with HIV suffer a higher burden of cardiovascular diseases. Traditional cardiovascular risk scores consistently underestimate cardiovascular risk in this population. Subsets of microRNAs (miRNAs) are differentially expressed among individuals with cardiovascular disease and individuals infected with HIV. However, no study has clarified whether specific miRNAs may be biomarkers for cardiovascular disease in individuals with HIV. DESIGN/METHODS We compared the miRNA expression profiles of 34 HIV positive individuals who had experienced clinically adjudicated Type I myocardial infarctions (MI) with the profiles of 76 HIV positive controls matched by traditional cardiovascular risk factors and HIV-specific measures. Using the elastic net algorithm, we selected miRNAs most strongly associated with incident MI and then used conditional Cox proportional hazards regression and cross-validation to evaluate miRNAs and their association with incident MI. We evaluated whether miRNA markers would improve risk classification relative to the Framingham Risk Score. RESULTS Higher miR-125a-5p and miR-139-5p expression levels were each associated with increased risk of developing MI after adjustment for Framingham Risk Score and HIV-related factors (HR 2.43, p = 0.018; HR 2.13, p = 0.048, respectively). Compared to the Framingham Risk Score alone, adding expression levels of miR-125a-5p or miR-139-5p resulted in an integrated discrimination improvement of 10.1% or 5.8% respectively. CONCLUSIONS MiR-125a-5p and miR-139-5p, transcripts known to be differentially expressed in HIV positive individuals, may serve as unique biomarkers predictive of cardiovascular disease in these patients and may help clarify processes due to HIV infection that contribute to cardiovascular pathology in this population.
Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes

Castellano et al. provide the first comparison of the full distribution of fitness effects (including deleterious, neutral but also beneficial mutations) in the great apes. The authors investigate which aspects of the full DFE are likely. The distribution of fitness effects (DFE) is central to many questions in evolutionary biology. However, little is known about the differences in DFE between closely related species. We use >9000 coding genes orthologous one-to-one across great apes, gibbons, and macaques to assess the stability of the DFE across great apes. We use the unfolded site frequency spectrum of polymorphic mutations (n = 8 haploid chromosomes per population) to estimate the DFE. We find that the shape of the deleterious DFE is strikingly similar across great apes. We confirm that effective population size (Ne) is a strong predictor of the strength of negative selection, consistent with the nearly neutral theory. However, we also find that the strength of negative selection varies more than expected given the differences in Ne between species. Across species, mean fitness effects of new deleterious mutations covaries with Ne, consistent with positive epistasis among deleterious mutations. We find that the strength of negative selection for the smallest populations, bonobos and western chimpanzees, is higher than expected given their Ne. This may result from a more efficient purging of strongly deleterious recessive variants in these populations. Forward simulations confirm that these findings are not artifacts of the way we are inferring Ne and DFE parameters. All findings are replicated using only GC-conservative mutations, thereby confirming that GC-biased gene conversion is not affecting our conclusions.
Lgr5+ pericentral hepatocytes are self-maintained in normal liver regeneration and susceptible to hepatocarcinogenesis

Significance Liver has a remarkable regenerative capacity following injuries. However, the cellular dynamics of how hepatocytes are replenished during homeostasis and upon liver injuries remains largely unclear. By using genetic lineage tracing strategies on rare Lgr5+ hepatocytes surrounding the central veins of the liver lobule, this study shows that Lgr5+ hepatocytes are self-maintained during normal homeostasis and various liver injuries, and contributed to hepatocarcinogesis in two different hepatocellular carcinoma (HCC) models. Our findings provide an insight on hepatocyte regeneration under homeostasis and liver injuries and uncover Lgr5+ hepatocytes as potential cellular origin in HCC development. Emerging evidence suggests that hepatocytes are primarily maintained by self-renewal during normal liver homeostasis, as well as in response to a wide variety of hepatic injuries. However, how hepatocytes in distinct anatomic locations within the liver lobule are replenished under homeostasis and injury-induced regeneration remains elusive. Using a newly developed bacterial artificial chromosome (BAC)-transgenic mouse model, we demonstrate that Lgr5 expression in the liver is restricted to a unique subset of hepatocytes most adjacent to the central veins. Genetic lineage tracing revealed that pericentral Lgr5+ hepatocytes have a long lifespan and mainly contribute to their own lineage maintenance during postnatal liver development and homeostasis. Remarkably, these hepatocytes also fuel the regeneration of their own lineage during the massive and rapid regeneration process following two-thirds partial hepatectomy. Moreover, Lgr5+ hepatocytes are found to be the main cellular origin of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) and are highly susceptible to neoplastic transformation triggered by activation of Erbb pathway. Our findings establish an unexpected self-maintaining mode for a defined subset of hepatocytes during liver homeostasis and regeneration, and identify Lgr5+ pericentral hepatocytes as major cells of origin in HCC development.
Association of Race/Ethnicity With Emergency Department Destination of Emergency Medical Services Transport

Key Points Question Are racial/ethnic minorities who use emergency medical services transported to the same emergency department as white residents living in the same zip code? Findings In this cohort study of 864 750 Medicare enrollees from 4175 zip codes, the proportion of white patients transported to the reference (or most frequent) emergency department destination was high (61.3%), compared with the proportion of black patients (difference of −5.3%) and Hispanic patients (difference of −2.5%). Meaning This study suggests that emergency department destination is substantially different on the basis of the race/ethnicity of patients living in the same zip code.
Interplay of the long axis of the hippocampus and ventromedial prefrontal cortex in schema‐related memory retrieval

When new information is relevant to prior knowledge or schema, it can be learned and remembered better. Rodent studies have suggested that the hippocampus and ventromedial prefrontal cortex (vmPFC) are important for processing schema‐related information. However, there are inconsistent findings from human studies on the involvement of the hippocampus and its interaction with the vmPFC in schema‐related memory retrieval. To address these issues, we used a human analog of the rodent spatial schema task to compare brain activity during immediate retrieval of paired associations (PAs) in schema‐consistent and schema‐inconsistent conditions. The results showed that the anterior hippocampus was more involved in retrieving PAs in the schema‐consistent condition than in the schema‐inconsistent condition. Connectivity analyses showed that the anterior hippocampus had stronger coupling with the vmPFC when the participants retrieved newly learned PAs successfully in the schema‐consistent (vs. schema‐inconsistent) condition, whereas the coupling of the posterior hippocampus with the vmPFC showed the opposite. Taken together, the results shed light on how the long axis of the hippocampus and vmPFC interact to serve memory retrieval via different networks that differ by schema condition.
A Fifteen-Year Analysis of Rare Isolated Fallopian Tube Torsions in Adolescent Children: A Case Series

Isolated tubal torsions presenting to the emergency department are a very rare cause of pediatric acute abdominal pain. Since making the diagnosis early is of importance in terms of affecting tubal damage and fertility, we aimed to evaluate cases of isolated tubal torsions in light of the literature. This study included 10 patients under 18 years of age who presented to the emergency department with abdominal pain between January 2003 and December 2018. The mean age was 14.5 ± 1.43 years (range: 12–17 years). The demographic characteristics, surgical findings and techniques, and concomitant pathology results of these patients were retrospectively evaluated. The reason for presenting to the emergency department for the 10 patients included in the study was abdominal pain. The mean duration of hospital admission with pain was 4.97 days. The onset of pain was less than 24 h in seven patients (70%) and more than 24 h in three patients (30%). Of the patients, nine (90%) had tenderness in the lower abdominal quadrant, five (5%) had defense, and three (30%) had rebound. Nausea, vomiting and leukocytosis were present in 50% of the cases. Right and left tubal involvement of the cases was equal. Seven (70%) of the isolated tubal torsions were accompanied by paraovarian cysts. Eight patients (80%) underwent open surgery and two (20%) underwent laparoscopic intervention. Detorsion was performed on five (50%) patients and salpingectomy was performed on five (50%) patients. Isolated tubal torsion should be considered in children presenting with acute abdominal pain in early adolescence. Early diagnosis is important for the preservation of fertility.
The Microbiome and Aging.

Aging is a natural process of organismal decay that underpins the development of myriad diseases and disorders. Extensive efforts have been made to understand the biology of aging and its regulation, but most studies focus solely on the host organism. Considering the pivotal role of the microbiota in host health and metabolism, we propose viewing the host and its microbiota as a single biological entity whose aging phenotype is influenced by the complex interplay between host and bacterial genetics. In this review we present how the microbiota changes as the host ages, but also how the intricate relationship between host and indigenous bacteria impacts organismal aging and life span. In addition, we highlight other microbiota-dependent mechanisms that potentially regulate aging, and present experimental animal models for addressing these questions. Importantly, we propose microbiome dysbiosis as an additional hallmark and biomarker of aging. Expected final online publication date for the Annual Review of Genetics, Volume 53 is November 23, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice

The metal transporters ZIP14 and ZnT10 play key physiological roles in maintaining manganese (Mn) homeostasis. However, in vivo regulation of these two transporters by Mn is not understood. Here, we examined how dietary Mn intake regulates ZIP14 and ZnT10 by feeding mice a low-Mn diet, a control diet, or a high-Mn diet for 6 weeks. Inductively coupled plasma mass spectrometry was used to measure Mn and iron (Fe) levels. ZIP14 and ZnT10 protein levels were measured by western blot analysis. While mice on the high-Mn diet exhibited significantly higher levels of Mn in the blood, liver, and brain, the low-Mn diet group did not display matching reductions, indicating that high Mn intake is more effective in disrupting Mn homeostasis in mice. Additionally, Fe levels were only slightly altered, suggesting independent transport mechanisms for Mn and Fe. In the high-Mn diet group, ZIP14 and ZnT10 were both upregulated in the liver, as well as in the small intestine, indicating a coordinated role for these transporters in Mn excretion. Unexpectedly, this upregulation only occurred in male mice, with the exception of hepatic ZIP14, providing new insight into mechanisms behind widely observed sex differences in Mn homeostasis.
If Cemeteries Could Talk … A Discourse-Analytical Analysis of Epitaphs

Death discourse provides interesting material to determine how societies and cultures cope with death and the sorrow of losing a beloved one. Several aspects can be analyzed: content, language, design, and so on. This article describes a diachronic bottom-up analysis of the metaphorical language in 150 epitaphs from Belgian cemeteries. The analysis allows us to determine whether attitudes toward death and the taboo to talk directly about it have changed. Based on the existing frameworks, 13 recurring metaphors were identified and analyzed. Their occurrences are linked to the period in which they were written and the age and the gender of the deceased. Epitaphs are a stable genre on all levels of analysis. The results indicate that people are still reluctant to talk in a straightforward way about death as metaphors with positive connotations prevail.