Miracle-dz/UniFAR-FTUs huggingface dataset:
Weight-independent effects of roux-en-Y gastric bypass on glucose homeostasis via melanocortin-4 receptors in mice and humans.

BACKGROUND & AIMS Roux-en-Y gastric bypass (RYGB) improves glucose homeostasis independently of changes in body weight by unknown mechanisms. Melanocortin-4 receptors (MC4R) have weight-independent effects on glucose homeostasis, via autonomic neurons, and also might contribute to weight loss after RYGB. We investigated whether MC4Rs mediate effects of RYGB, such as its weight-independent effects on glucose homeostasis, in mice and humans. METHODS We studied C57BL/6 mice with diet-induced obesity, MC4R-deficient mice, and mice that re-express MC4R specifically in autonomic neurons after RYGB or sham surgeries. We also sequenced the MC4R locus in patients undergoing RYGB to investigate diabetes resolution in carriers of rare MC4R variants. RESULTS MC4Rs in autonomic brainstem neurons (including the parasympathetic dorsal motor vagus) mediated improved glucose homeostasis independent of changes in body weight. In contrast, MC4Rs in cholinergic preganglionic motor neurons (sympathetic and parasympathetic) mediated RYGB-induced increased energy expenditure and weight loss. Increased energy expenditure after RYGB is the predominant mechanism of weight loss and confers resistance to weight gain from a high-fat diet, the effects of which are MC4R-dependent. MC4R-dependent effects of RYGB still occurred in mice with Mc4r haplosufficiency, and early stage diabetes resolved at a similar rate in patients with rare variants of MC4R and noncarriers. However, carriers of MC4R (I251L), a rare variant associated with increased weight loss after RYGB and increased basal activity in vitro, were more likely to have early and weight-independent resolution of diabetes than noncarriers, indicating a role for MC4Rs in the effects of RYGB. CONCLUSIONS MC4Rs in autonomic neurons mediate beneficial effects of RYGB, including weight-independent improved glucose homeostasis, in mice and humans.
Human–Robot Similarity and Willingness to Work with a Robotic Co-worker

Organizations now face a new challenge of encouraging their employees to work alongside robots. In this paper, we address this problem by investigating the impacts of human–robot similarity, trust in a robot, and the risk of physical danger on individuals’ willingness to work with a robot and their willingness to work with a robot over a human co-worker. We report the results from an online experimental study involving 200 participants. Results showed that human–robot similarity promoted trust in a robot, which led to willingness to work with robots and ultimately willingness to work with a robot over a human co-worker. However, the risk of danger moderated not only the positive link between the surface-level similarity and trust in a robot, but also the link between intention to work with the robot and willingness to work with a robot over a human coworker. We discuss several implications for the theory of human–robot interaction and design of robots.
Fast, Accurate and Automatic Ancient Nucleosome and Methylation Maps with epiPALEOMIX

The first epigenomes from archaic hominins (AH) and ancient anatomically modern humans (AMH) have recently been characterized, based, however, on a limited number of samples. The extent to which ancient genome-wide epigenetic landscapes can be reconstructed thus remains contentious. Here, we present epiPALEOMIX, an open-source and user-friendly pipeline that exploits post-mortem DNA degradation patterns to reconstruct ancient methylomes and nucleosome maps from shotgun and/or capture-enrichment data. Applying epiPALEOMIX to the sequence data underlying 35 ancient genomes including AMH, AH, equids and aurochs, we investigate the temporal, geographical and preservation range of ancient epigenetic signatures. We first assess the quality of inferred ancient epigenetic signatures within well-characterized genomic regions. We find that tissue-specific methylation signatures can be obtained across a wider range of DNA preparation types than previously thought, including when no particular experimental procedures have been used to remove deaminated cytosines prior to sequencing. We identify a large subset of samples for which DNA associated with nucleosomes is protected from post-mortem degradation, and nucleosome positioning patterns can be reconstructed. Finally, we describe parameters and conditions such as DNA damage levels and sequencing depth that limit the preservation of epigenetic signatures in ancient samples. When such conditions are met, we propose that epigenetic profiles of CTCF binding regions can be used to help data authentication. Our work, including epiPALEOMIX, opens for further investigations of ancient epigenomes through time especially aimed at tracking possible epigenetic changes during major evolutionary, environmental, socioeconomic, and cultural shifts.
Efficacy and safety of Tripterygium wilfordii Hook F for CKD in Mainland China: A systematic review and meta‐analysis

Tripterygium wilfordii Hook F (TwHF) is a promising Chinese traditional medicine used to significantly reduce proteinuria and improve renal function. However, its efficacy and safety in treatment of chronic kidney disease need to be further explored in order to promote its application in clinics. This review compared the efficacy and safety of TwHF with the placebo, conventional Western medicine and other immunosuppressive medicine in a range of kidney disorders. One hundred three randomized controlled trials were included. TwHF therapy decreased 24‐hr proteinuria by 0.59 g/day (95% confidence interval [CI; −0.68, −0.50]), serum creatinine level by 1.93 μmol/L (95% CI [−3.69, −0.17]), and blood urea nitrogen level by 0.24 mmol/L (95% CI [−0.41, −0.07]); increased the total effective rate by 27% (95% CI [1.24, 1.30]); and decreased the incidence of adverse reactions by 19% (95% CI [0.68, 0.96]) overall. Meta regression results showed that the duration of therapy and mean age of participants were the major sources of high heterogeneity. Sensitivity analysis demonstrated that our statistic results were relatively stable and credible. The present findings suggested that TwHF possibly has nephroprotective effects by decreasing proteinuria, serum creatinine level, and blood urea nitrogen level and no more adverse reactions compared with control group in most kidney disorders. However, these findings still need to be further confirmed by high‐quality trials.
Strongly enhanced bacterial bioluminescence with the ilux operon for single-cell imaging

Significance The emission of light generated in a process referred to as bioluminescence can be used for imaging of living cells over long timespans without phototoxicity or bleaching. The amounts of light produced in the bioluminescence process are very low, and exogenous substrate molecules are often required. We improved the brightness of bacterial bioluminescence, a system that features the advantage that all of the required molecular components are genetically encoded within a single operon. Consequently, we have engineered an improved operon ilux, which enables long-term visualization of single bacterial cells while simultaneously providing information about cellular viability. Bioluminescence imaging of single cells is often complicated by the requirement of exogenous luciferins that can be poorly cell-permeable or produce high background signal. Bacterial bioluminescence is unique in that it uses reduced flavin mononucleotide as a luciferin, which is abundant in all cells, making this system purely genetically encodable by the lux operon. Unfortunately, the use of bacterial bioluminescence has been limited by its low brightness compared with other luciferases. Here, we report the generation of an improved lux operon named ilux with an approximately sevenfold increased brightness when expressed in Escherichia coli; ilux can be used to image single E. coli cells with enhanced spatiotemporal resolution over several days. In addition, since only metabolically active cells produce bioluminescent signal, we show that ilux can be used to observe the effect of different antibiotics on cell viability on the single-cell level.
HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development

Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1-dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles. This pathway was discovered through the creation and analysis of Hmmr-knockout mice, which suffer neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues. HMMR over-expression in immortalized cancer cells induces phenotypes consistent with an increase in active Ran including defects in spindle orientation. These data identify an essential role for HMMR in the PLK1-dependent regulatory pathway that orients progenitor cell division and supports neural development.
Predictors of Restenosis Following Carotid Angioplasty and Stenting

Background and Purpose— Restenosis after carotid angioplasty (with or without stent) is associated with increased rate of stroke and death. Our aim was to determine risk and predictive factors related to carotid restenosis post carotid angioplasty and its association to recurrent cerebrovascular events. Methods— All consecutive patients with carotid stenosis treated with angioplasty (n=1060) in a single University Hospital were included (from 2002 to 2013). Follow-up was done prospectively evaluating restenosis, ipsilateral stroke, or death. Restenosis was defined as a narrowing of ≥70% of a previously treated vessel evaluated by ultrasonography. Results— Of the 1060 patients treated, 9.2% (97) of patients experienced restenosis during follow up (median 12 [9–32] months). Occurrence of restenosis was associated with ipsilateral stroke during follow-up (P=0.049). After Cox regression analysis, hypertension (hazard ratio, 6.2 [1.9–19.9]; P=0.002), impaired vasoreactivity (hazard ratio, 1.7 [1.09–2.8]; P=0.019), and angioplasty without stent (hazard ratio, 2.9 [1.2–6.8]; P=0.012) were independent risk predictors of >70% restenosis. Conclusions— Carotid restenosis after carotid angioplasty is associated with ipsilateral stroke occurrence. In our sample, hypertension, angioplasty without stent, and impaired vasoreactivity identify patients at high risk of restenosis and could help to select patients for follow-up ultrasonography imaging.
The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation

Metabolic syndrome (MetS) is a known complication after hematopoietic stem cell transplantations (HSCT) that contributes to long‐term morbidity. We assessed the prevalence of components of the MetS in pediatric survivors of allogeneic HSCT and identified associated risk factors. Thirty‐eight patients, median age at HSCT, 8.5 years, were evaluated at a median of 3.9 years post‐HSCT. Overweight or obesity was seen in 23.7% of the patients, 15.8% had hypertension, 15.8% had hypertriglyceridemia, and 13% had low high‐density lipoprotein cholesterol levels according to age and gender. Four (10.5%) met the criteria of MetS; all were transplanted for malignant disease. Twelve patients (31.6%) had at least one component of the MetS. The 5‐year probability of developing components of the MetS revealed that patients with BMI‐Z score ≥0 at HSCT were significantly at higher risk than those with lower BMI‐Z. Patients who developed components of the MetS had higher levels of insulin, homeostasis model assessment, uric acid, leptin, and lower adiponectin levels. Multivariable regression analysis revealed that BMI‐Z‐score >1.036 at time of evaluation was associated with 4.3‐fold increased risk (P=.050) and adiponectin levels ≤6 μg/mL were associated with 6.7‐fold increased risk of develop components of the MetS (P=.007). Overweight and obesity and adiponectin levels may be useful as markers in HSCT survivors.
Resveratrol-Induced Changes in MicroRNA Expression in Primary Human Fibroblasts Harboring Carnitine-Palmitoyl Transferase-2 Gene Mutation, Leading to Fatty Acid Oxidation Deficiency

Carnitine palmitoyltransferase-2 (CPT2) is a mitochondrial enzyme involved in long-chain fatty acid entry into mitochondria for their β-oxidation and energy production. Two phenotypes are associated with the extremely reduced CPT2 activity in genetically deficient patients: neonatal lethality or, in milder forms, myopathy. Resveratrol (RSV) is a phytophenol produced by grape plant in response to biotic or abiotic stresses that displays anti-oxidant properties, in particular through AP-1, NFκB, STAT-3, and COX pathways. Some beneficiary effects of RSV are due to its modulation of microRNA (miRNA) expression. RSV can enhance residual CPT2 activities in human fibroblasts derived from CPT2-deficient patients and restores normal fatty acid oxidation rates likely through stimulation of mitochondrial biogenesis. Here, we report changes in miRNA expression linked to CPT2-deficiency, and we identify miRNAs whose expression changed following RSV treatment of control or CPT2-deficient fibroblasts isolated from patients. Our findings suggest that RSV consumption might exert beneficiary effects in patients with CPT2-deficiency.
Proteomics of Maize Root Development

Maize forms a complex root system with structurally and functionally diverse root types that are formed at different developmental stages to extract water and mineral nutrients from soil. In recent years proteomics has been intensively applied to identify proteins involved in shaping the three-dimensional architecture and regulating the function of the maize root system. With the help of developmental mutants, proteomic changes during the initiation and emergence of shoot-borne, lateral and seminal roots have been examined. Furthermore, root hairs were surveyed to understand the proteomic changes during the elongation of these single cell type structures. In addition, primary roots have been used to study developmental changes of the proteome but also to investigate the proteomes of distinct tissues such as the meristematic zone, the elongation zone as well as stele and cortex of the differentiation zone. Moreover, subcellular fractions of the primary root including cell walls, plasma membranes and secreted mucilage have been analyzed. Finally, the superior vigor of hybrid seedling roots compared to their parental inbred lines was studied on the proteome level. In summary, these studies provide novel insights into the complex proteomic interactions of the elaborate maize root system during development.
Criteria for early generation selection in wheat breeding programmes for improving protein productivity

Correlations of % grain protein, protein content/grain and protein yield/unit area with grain yield, yield components and harvest index were calculated for 21 spring wheat cultivars. % grain protein was negatively correlated with grain yield, grain number and harvest index. Protein content/grain was positively correlated with grain wt. and negatively with grain number. Grain protein yield/unit area was positively correlated with grain yield, wt. and number, harvest index and % grain protein and provided the best criterion for selection for improved protein productivity. It does not take account of amino acid composition or protein digestibility.
Control of Recombination Directionality by the Listeria Phage A118 Protein Gp44 and the Coiled-Coil Motif of Its Serine Integrase

ABSTRACT The serine integrase of phage A118 catalyzes integrative recombination between attP on the phage and a specific attB locus on the chromosome of Listeria monocytogenes, but it is unable to promote excisive recombination between the hybrid attL and attR sites found on the integrated prophage without assistance by a recombination directionality factor (RDF). We have identified and characterized the phage-encoded RDF Gp44, which activates the A118 integrase for excision and inhibits integration. Gp44 binds to the C-terminal DNA binding domain of integrase, and we have localized the primary binding site to be within the mobile coiled-coil (CC) motif but distinct from the distal tip of the CC that is required for recombination. This interaction is sufficient to inhibit integration, but a second interaction involving the N-terminal end of Gp44 is also required to activate excision. We provide evidence that these two contacts modulate the trajectory of the CC motifs as they extend out from the integrase core in a manner dependent upon the identities of the four att sites. Our results support a model whereby Gp44 shapes the Int-bound complexes to control which att sites can synapse and recombine. IMPORTANCE Serine integrases mediate directional recombination between bacteriophage and bacterial chromosomes. These highly regulated site-specific recombination reactions are integral to the life cycle of temperate phage and, in the case of Listeria monocytogenes lysogenized by A118 family phage, are an essential virulence determinant. Serine integrases are also utilized as tools for genetic engineering and synthetic biology because of their exquisite unidirectional control of the DNA exchange reaction. Here, we identify and characterize the recombination directionality factor (RDF) that activates excision and inhibits integration reactions by the phage A118 integrase. We provide evidence that the A118 RDF binds to and modulates the trajectory of the long coiled-coil motif that extends from the large carboxyl-terminal DNA binding domain and is postulated to control the early steps of recombination site synapsis.
Pathophysiology and Pathogenesis of Visceral Fat Obesity

Based on the analysis of fat distribution by CT scanning, we have proposed a classification of obesity: visceral fat obesity, in which fat accumulation is predominant in the intra-abdominal cavity. This type of obesity is more frequently accompanied by disorders of glucose and lipid metabolism, and also with hypertension, than subcutaneous fat obesity. We also showed that almost 90% of obese patients with ischemic heart disease have visceral fat accumulation. From clinical and basic experiments, aging, imbalance of sex hormone, overintake of sucrose and lack of physical exercise have been suggested to be major factors for visceral fat accumulation. Since intra-abdominal fat (mesenteric and omentum fat) have been show to have high activities of both lipogenesis and lipolysis, its accumulation induces a high content of free fatty acids, a product of lipolysis, in portal circulation which goes into the liver directly. Excess free fatty acid may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis.
Undisclosed conflicts of interest among biomedical textbook authors

ABSTRACT Background: Textbooks are a formative resource for health care providers during their education and are also an enduring reference for pathophysiology and treatment. Unlike the primary literature and clinical guidelines, biomedical textbook authors do not typically disclose potential financial conflicts of interest (pCoIs). The objective of this study was to evaluate whether the authors of textbooks used in the training of physicians, pharmacists, and dentists had appreciable undisclosed pCoIs in the form of patents or compensation received from pharmaceutical or biotechnology companies. Methods: The most recent editions of six medical textbooks, Harrison's Principles of Internal Medicine (HarPIM), Katzung and Trevor's Basic and Clinical Pharmacology (KatBCP), the American Osteopathic Association's Foundations of Osteopathic Medicine (AOAFOM), Remington: The Science and Practice of Pharmacy (RemSPP), Koda-Kimble and Young's Applied Therapeutics (KKYAT), and Yagiela's Pharmacology and Therapeutics for Dentistry (YagPTD), were selected after consulting biomedical educators for evaluation. Author names (N = 1,152, 29.2% female) were submitted to databases to examine patents (Google Scholar) and compensation (ProPublica's Dollars for Docs [PDD]). Results: Authors were listed as inventors on 677 patents (maximum/author = 23), with three-quarters (74.9%) to HarPIM authors. Females were significantly underrepresented among patent holders. The PDD 2009–2013 database revealed receipt of US$13.2 million, the majority to (83.9%) to HarPIM. The maximum compensation per author was $869,413. The PDD 2014 database identified receipt of $6.8 million, with 50.4% of eligible authors receiving compensation. The maximum compensation received by a single author was $560,021. Cardiovascular authors were most likely to have a PDD entry and neurologic disorders authors were least likely. Conclusion: An appreciable subset of biomedical authors have patents and have received remuneration from medical product companies and this information is not disclosed to readers. These findings indicate that full transparency of financial pCoI should become a standard practice among the authors of biomedical educational materials.
The Relationship Between Cardiac Conduction Times, Cardiovascular Risk Factors, and Inflammation in Patients with Early Arthritis

Objective. To investigate the prevalence of conduction disorders in patients with early arthritis and the relationship with inflammation and traditional cardiovascular (CV) risk factors. Methods. Patients with rheumatoid arthritis (RA) have a 2-fold higher risk of sudden cardiac death, possibly owing to conduction disorders. This increased risk might already be present at the clinical onset of arthritis. Therefore, we assessed electrocardiography, blood pressure, 28-joint Disease Activity Score (DAS28), lipid profile, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level in 480 patients with early arthritis at baseline and after 1 year. Results. The prevalence of conduction disorders was 12.5%. Conduction times at baseline were not associated with DAS28, ESR, or CRP levels and did not change during antirheumatic treatment. Baseline and the improvement in DAS28 (European League Against Rheumatism response), ESR, and CRP were significantly associated with heart rate, lipid profile, and blood pressure. Elevated total cholesterol and blood pressure were associated with an increased QRS time. The change in heart rate differed 7.3 bpm between patients with the least versus largest DAS improvement. Conclusion. The prevalence of conduction disorders in patients with early arthritis was 12.5%, which is similar to the general population and was not associated with changes in inflammation markers. However, a high cholesterol was associated with a prolonged QRS time. Therefore, the emphasis of CV risk management in arthritis should not be only on treatment of disease activity but also on traditional CV risk factors. The relationship between the improvement in disease activity and heart rate is remarkable because this could imply a 10-year CV mortality risk difference of 24%.