Miracle-dz/UniFAR-FTUs huggingface dataset:
Inducible Loss of the Aryl Hydrocarbon Receptor Activates Perigonadal White Fat Respiration and Brown Fat Thermogenesis via Fibroblast Growth Factor 21

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor highly expressed in hepatocytes. Researchers have employed global and liver-specific conditional Ahr knockout mouse models to characterize the physiological roles of the AHR; however, the gestational timing of AHR loss in these models can complicate efforts to distinguish the direct and indirect effects of post-gestational AHR deficiency. Utilizing a novel tamoxifen-inducible AHR knockout mouse model, we analyzed the effects of hepatocyte-targeted AHR loss in adult mice. The data demonstrate that AHR deficiency significantly reduces weight gain and adiposity, and increases multilocular lipid droplet formation within perigonadal white adipose tissue (gWAT). Protein and mRNA expression of fibroblast growth factor 21 (FGF21), an important hepatokine that activates thermogenesis in brown adipose tissue (BAT) and gWAT, significantly increases upon AHR loss and correlates with a significant increase of BAT and gWAT respiratory capacity. Confirming the role of FGF21 in mediating these effects, this phenotype is reversed in mice concomitantly lacking AHR and FGF21 expression. Chromatin immunoprecipitation analyses suggest that the AHR may constitutively suppress Fgf21 transcription through binding to a newly identified xenobiotic response element within the Fgf21 promoter. The data demonstrate an important AHR-FGF21 regulatory axis that influences adipose biology and may represent a “druggable” therapeutic target for obesity and its related metabolic disorders.
Surgical desensitisation of the mechanoreceptors in Müller's muscle relieves chronic tension-type headache caused by tonic reflexive contraction of the occipitofrontalis muscle in patients with aponeurotic blepharoptosis

Abstract Proprioceptively innervated intramuscular connective tissues in Müller's muscle function as exterior mechanoreceptors to induce reflex contraction of the levator and occipitofrontalis muscles. In aponeurotic blepharoptosis, since the levator aponeurosis is disinserted from the tarsus, stretching of the mechanoreceptors in Müller's muscle is increased even on primary gaze to induce phasic and tonic reflexive contraction of the occipitofrontalis muscle. It was hypothesised that in certain patients with aponeurotic blepharoptosis, the presence of tonic reflexive contraction of the occipitofrontalis muscle due to the sensitised mechanoreceptors in Müller's muscle, can cause chronic tension-type headache (CTTH) associated with occipitofrontalis tenderness. To verify this hypothesis, this study evaluated (1) what differentiates patients with CTTH from patients without CTTH, (2) how pharmacological contraction of Müller's smooth muscle fibres as a method for desensitising the mechanoreceptors in Müller's muscle affects electromyographic activity of the frontalis muscle, and (3) how surgical aponeurotic reinsertion to desensitise the mechanoreceptors in Müller's muscle electromyographically or subjectively affects activities of the occipitofrontalis muscle or CTTH. It was found that patients had sustained CTTH when light eyelid closure did not markedly reduce eyebrow elevation. However, pharmacological contraction of Müller's smooth muscle fibres or surgery to desensitise the mechanoreceptor electromyographically reduced the tonic contraction of the occipitofrontalis muscle on primary gaze and subjectively relieved aponeurotic blepharoptosis-associated CTTH. Over-stretching of the mechanoreceptors in Müller's muscle on primary gaze may induce CTTH due to tonic reflexive contraction of the occipitofrontalis muscle. Therefore, surgical desensitisation of the mechanoreceptors in Müller's muscle appears to relieve CTTH.
Placental Growth Factor Regulates Cardiac Inflammation Through the Tissue Inhibitor of Metalloproteinases-3/Tumor Necrosis Factor-&agr;–Converting Enzyme Axis: Crucial Role for Adaptive Cardiac Remodeling During Cardiac Pressure Overload

Background— Heart failure is one of the leading causes of mortality and is primarily the final stage of several overload cardiomyopathies, preceded by an early adaptive hypertrophic response and characterized by coordinated cardiomyocyte growth, angiogenesis, and inflammation. Therefore, growth factors and cytokines have to be critically regulated during cardiac response to transverse aortic constriction. Interestingly, the dual properties of placental growth factor as an angiogenic factor and cytokine make it a candidate to participate in cardiac remodeling in response to hemodynamic overload. Methods and Results— After transverse aortic constriction, placental growth factor knockout mice displayed a dysregulation of cardiac remodeling, negatively affecting muscle growth. Molecular insights underscored that this effect was ascribable mainly to a failure in the establishment of adequate inflammatory response owing to an impaired activity of tumor necrosis factor-&agr;–converting enzyme. Interestingly, after transverse aortic constriction, placental growth factor knockout mice had strongly increased levels of tissue inhibitor of metalloproteinases-3, the main natural TACE inhibitor, thus indicating an unbalance of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-&agr;–converting enzyme axis. Strikingly, when we used an in vivo RNA interference approach to reduce tissue inhibitor of metalloproteinases-3 levels in placental growth factor knockout mice during transverse aortic constriction, we obtained a complete phenotype rescue of early dilated cardiomyopathy. Conclusions— Our results demonstrate that placental growth factor finely tunes a balanced regulation of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor-&agr;–converting enzyme axis and the consequent TNF-&agr; activation in response to transverse aortic constriction, thus allowing the establishment of an inflammatory response necessary for adaptive cardiac remodeling.
D-Methionine Ameliorates Cisplatin-Induced Muscle Atrophy via Inhibition of Muscle Degradation Pathway

Cisplatin induces anorexia, weight loss, loss of adipose tissue, skeletal muscle atrophy, and serious adverse effects that can cause premature termination of chemotherapy. The aim of this study was to use an animal model to assess cisplatin therapy (3 cycles) with and without d-methionine to investigate its protective effects on cisplatin-induced anorexia and skeletal muscle wasting. Wistar rats were divided into 3 groups and treated as follows: saline as control (group 1), intraperitoneal cisplatin once a week for 3 weeks (group 2), and intraperitoneal cisplatin once a week for 3 weeks plus oral administration of d-methionine (group 3). Tissue somatic index (TSI), gastric emptying index (GEI), and feeding efficiency were measured. Both hepatic lipid metabolism and muscle atrophy-related gene expressions and C2C12 myotubes were determined by polymerase chain reaction. Micro–computed tomography (micro-CT) was used to conduct assessment of bone microarchitecture indices. Pathological changes of the gastric mucosa were assessed by hematoxylin and eosin staining after euthanizing the animals. d-Methionine increased food intake, weight gain, gastric emptying, and feeding efficiency, as well as decrease stomach contents, after cisplatin injections. Cisplatin caused shortening of myofibers. Cisplatin-induced muscle mass wasting was mediated by the elevation of mRNA expressions of MAFbx and MuRF-1 in ubiquitin ligases in muscle tissue homogenate. The mRNA expressions of MyoD and myogenin, markers of muscle differentiation, declined following cisplatin administration. The administration of d-methionine not only led to significant improvements in myofiber diameter and cross-sectional fiber areas but also reversed muscle atrophy-related gene expression. However, there were no significant changes in stomach histology or microarchitecture of trabecular bone among the study groups. The results indicate that d-methionine has an appetite-enhancing effect and ameliorates cisplatin-induced adipose and muscle tissue loss during cisplatin-based chemotherapy.
Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity

We computed the network of channels of the 3A4 isoform of the cytochrome P450 (CYP) on the basis of 16 crystal structures extracted from the Protein Data Bank (PDB). The calculations were performed with version 2 of the CCCPP software that we developed for this research project. We identified the minimal cost paths (MCPs) output by CCCPP as probable ways to access to the buried active site. The algorithm of calculation of the MCPs is presented in this paper, with its original method of visualization of the channels. We found that these MCPs constitute four major channels in CYP3A4. Among the many channels proposed by Cojocaru et al. in 2007, we found that only four of them open in 3A4. We provide a refined description of these channels together with associated quantitative data.
Prediction of Silent Ischemic Lesions after Carotid Artery Stenting Using Virtual Histology Intravascular Ultrasound

Background: A major concern with carotid artery stenting (CAS) is the potential for cerebral embolism. The purpose of this study was to determine whether virtual histology intravascular ultrasound (VH-IVUS) can predict the risk of a silent ischemic lesion after CAS. Methods: We performed CAS in 45 patients with carotid stenosis. Before CAS, we assessed plaque characteristics by VH-IVUS. We also performed diffusion-weighted magnetic resonance imaging of the brain before and after CAS to detect newly appearing ipsilateral silent ischemic lesions (NISIL). Results: In the patient group that was positive for NISIL (P group: n = 18), the relative fibrofatty (FF) area identified by VH-IVUS in 5 cross-sections including the most stenotic lesion was significantly larger than that in areas of the NISIL-negative group (N group: n = 27; 32.7 ± 13.2 and 18.3 ± 9.8%, respectively; p < 0.001). The relative fibrous area was significantly lower in the P group than in the N group (59.2 ± 9.5 and 74.6 ± 9.1%, respectively; p < 0.001). There were no differences in the relative dense calcium and necrotic core areas between the P and N groups. From the analysis of receiver operating characteristic curves, most reliable cutoff values for predicting NISIL were a relative FF area of 30% in the most stenotic lesion. In multivariate logistic regression analysis, the relative FF area was an independent predictor of NISIL (p = 0.005). Conclusions: Quantitative tissue characterization of atherosclerotic lesions of carotid arteries using VH-IVUS was useful to predict NISIL after CAS. However, the positive predictive value determined by VH-IVUS was not superior to that determined by a noninvasive method.
Overcoming prey naiveté: Free‐living marsupials develop recognition and effective behavioral responses to alien predators in Australia

Naiveté in prey arises from novel ecological mismatches in cue recognition systems and antipredator responses following the arrival of alien predators. The multilevel naiveté framework suggests that animals can progress through levels of naiveté toward predator awareness. Alternatively, native prey may be preadapted to recognize novel predators via common constituents in predator odors or familiar predator archetypes. We tested predictions of these competing hypotheses on the mechanisms driving behavioral responses of native species to alien predators by measuring responses of native free‐living northern brown bandicoots (Isoodon macrourus) to alien red fox (Vulpes vulpes) odor. We compared multiple bandicoot populations either sympatric or allopatric with foxes. Bandicoots sympatric with foxes showed recognition and appropriate antipredator behavior toward fox odor via avoidance. On the few occasions bandicoots did visit, their vigilance significantly increased, and their foraging decreased. In contrast, bandicoots allopatric with foxes showed no recognition of this predator cue. Our results suggest that vulnerable Australian mammals were likely naïve to foxes when they first arrived, which explains why so many native mammals declined soon after fox arrival. Our results also suggest such naiveté can be overcome within a relatively short time frame, driven by experience with predators, thus supporting the multilevel naiveté framework.
PREVALENCE OF ANTIBODIES TO ORTHOPOXVIRUS IN WILD CARNIVORES OF NORTHWESTERN CHIHUAHUA, MEXICO.

The distribution of orthopoxviruses (OPXVs) across the North American continent is suggested to be widespread in a wide range of mammalian hosts on the basis of serosurveillance studies. To address the question of whether carnivores in northwestern Mexico are exposed to naturally circulating OPXVs, wild carnivores were collected by live trapping within four different habitat types during fall of 2013 and spring of 2014 within the Janos Biosphere Reserve in northwestern Chihuahua, Mexico. A total of 51 blood samples was collected for testing. Anti-OPXV immunoglobulin G enzyme-linked immunosorbent assay, western blot, and rapid fluorescent focus inhibition test (RFFIT) assays were conducted. About 47% (24/51) of the carnivores tested were seropositive for anti-OPXV binding antibodies and had presence of immunodominant bands indicative of OPXV infection. All samples tested were negative for rabies virus neutralizing antibodies by RFFIT, suggesting that the OPXV antibodies were due to circulating OPXV, and not from exposure to oral rabies vaccine (vaccinia-vectored rabies glycoprotein vaccine) bait distributed along the US-Mexico border. Our results indicated that there may be one or more endemic OPXV circulating within six species of carnivores in northwestern Mexico.
Cell Adhesion Molecules, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor in Patients with Non–Small Cell Lung Cancer Treated with Chemotherapy with or without Bevacizumab—an Eastern Cooperative Oncology Group Study

Background: E4599 was a phase II/phase III trial, in which 878 patients with advanced non–small cell lung cancer were randomized to carboplatin + paclitaxel (PC arm) or PC + bevacizumab (BPC arm). Survival and progression-free survival were superior on the BPC arm. The rationale for markers used in this correlative study was based on elevated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), soluble intercellular adhesion molecule (ICAM) and E-selectin in a variety of malignances and changes in response to endothelial cell apoptosis. Materials and Methods: Prospective correlates included measurements of pretreatment plasma VEGF, as well as pretreatment and week 7, bFGF, ICAM, and E-selectin. Low and high levels were defined as less than or equal to or more than the median. Results: E-selectin (P < 0.0001) showed a decrease and bFGF showed an increase (P = 0.004) from baseline at week 7, which were similar in both arms. Baseline ICAM showed significant associations with response and survival in both groups. Patients with low baseline ICAM had a higher response rate (32% versus 14%; P = 0.02), better overall survival (P = 0.00005), and better 1-year survival (65% versus 25%) than those with high ICAM, respectively, regardless of treatment arm. Patients with high VEGF levels were more likely to respond to BPC compared with PC, but this was not predictive of survival. The results also suggest a benefit from bevacizumab for patients with low baseline ICAM levels (53% reduction in the progression-free survival hazard rate). Conclusions: In this study, baseline ICAM levels were prognostic for survival and predictive of response to chemotherapy with or without bevacizumab. VEGF levels were predictive of response to bevacizumab but not survival.
Beverage consumption, appetite, and energy intake: what did you expect?

BACKGROUND Beverage consumption is implicated in the overweight/obesity epidemic through the weaker energy compensation response it elicits compared with solid food forms. However, plausible mechanisms are not documented. OBJECTIVE This study assessed the cognitive and sensory contributions of differential postingestive responses to energy- and macronutrient-matched liquid (in beverage form) and solid food forms and identifies physiologic processes that may account for them. DESIGN Fifty-two healthy adults [mean ± SD age: 24.7 ± 5.5 y; BMI (in kg/m(2)): 26.3 ± 6.3] completed this randomized, 4-arm crossover study. Participants consumed oral liquid and solid preloads that they perceived, through cognitive manipulation, to be liquid or solid in their stomach (ie, oral liquid/perceived gastric liquid, oral liquid/perceived gastric solid, oral solid/perceived gastric liquid, or oral solid/perceived gastric solid). However, all preloads were designed to present a liquid gastric challenge. Appetite, gastric-emptying and orocecal transit times, and selected endocrine responses were monitored for the following 4 h; total energy intake was also recorded. RESULTS Oral-liquid and perceived gastric-liquid preloads elicited greater postprandial hunger and lower fullness sensations, more rapid gastric-emptying and orocecal transit times, attenuated insulin and glucagon-like peptide 1 release, and lower ghrelin suppression than did responses after oral-solid and perceived gastric-solid treatments (all P < 0.05). Faster gastric-emptying times were significantly associated with greater energy intake after consumption of perceived gastric-liquid preloads (P < 0.05). Energy intake was greater on days when perceived gastric-liquid preloads were consumed than when perceived gastric solids were consumed (2311 ± 95 compared with 1897 ± 72 kcal, P = 0.007). CONCLUSIONS These data document sensory and cognitive effects of food form on ingestive behavior and identify physical and endocrine variables that may account for the low satiety value of beverages. They are consistent with findings that clear, energy-yielding beverages pose a particular risk for positive energy balance. This study was registered at clinicaltrials.gov as NCT01070199.
The smokeless tobacco habit and DNA damage: A systematic review and meta-analysis

Background The aim of this systematic review was to evaluate the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits. Material and Methods We searched PubMed, Scopus, Web of Science, LILACS, BBO and Cochrane Library and SIGLE. We also surveyed gray literature. We included only clinical trials that compare the frequency of micronuclei or other DNA damage in the oral mucosa of adults that have smokeless tobacco habits compared to adults that not have these habits. Quality assessments of the selected trials were evaluated by two independent reviewers, using the Effective Public Health Practice Project – (EPHPP) with modifications. Results After the database screening and removal of duplicates, 2574 studies were identified. After title screening, 172 studies remained, and this number was reduced to 25 after careful examination of the abstracts. The standardized mean difference of the frequency of micronuclei between groups was 1.88, with a 95% confidence interval of 1.40 to 2.36 (p< 0.00001). In all analyses heterogeneity was detected. Conclusions Despite the heterogeneity of studies, the frequency of micronuclei was significant bigger in adults who have the smokeless tobacco habit when compared to those not have this habit. The same occurred with the frequency of binucleated cells, karyolisis and karyorrhexis. Key words:Micronucleus tests, Tobacco, smokeless, DNA damage.
Brood Size Affects Future Reproduction in a Long-Lived Bird with Precocial Young

Estimation of trade-offs between current reproduction and future survival and fecundity of long-lived vertebrates is essential to understanding factors that shape optimal reproductive investment. Black brant geese (Branta bernicla nigricans) fledge more goslings, on average, when their broods are experimentally enlarged to be greater than the most common clutch size of four eggs. Thus, we hypothesized that the lesser frequency of brant clutches exceeding four eggs results, at least partially, from a future reduction in survival, breeding probability, or clutch size for females tending larger broods. We used an 8-year mark-recapture data set (Barker robust design) with 5 years of clutch and brood manipulations to estimate long-term consequences of reproductive decisions in brant. We did not find evidence of a trade-off between reproductive effort and true survival or future initiation date and clutch size. Rather, future breeding probability was maximized (0.92±0.03 [SE]) for manipulated females tending broods of four goslings and was lower for females tending smaller (one gosling; 0.63±0.09 [SE]) or larger (seven goslings; 0.52±0.15 [SE]) broods. Our results suggest that demographic trade-offs for female brant tending large broods may reduce the fitness value of clutches larger than four and, therefore, contribute to the paucity of larger clutches. The lack of a trade-off between reproductive effort and survival provides evidence that survival, to which fitness is most sensitive in long-lived animals, is buffered against temporal variation in brant.
Pharmacological Properties of Morus nigra L. (Black Mulberry) as A Promising Nutraceutical Resource

Mulberry plants belonging to the Moraceae family have been grown for the purpose of being the nutrient source for silk worm and raw materials for the preparation of jams, marmalades, vinegars, juices, wines, and cosmetics. Morus nigra L. (black mulberry) is native to Southwestern Asia, and it has been used as a traditional herbal medicine for animals and humans. In this article, recent research progress on various biological and pharmacological properties of extracts, fractions, and isolated active constituents from different parts of M. nigra are reviewed. M. nigra exhibited a wide-spectrum of biological and pharmacological therapeutic effects including antinociceptive, anti-inflammatory, antimicrobial, anti-melanogenic, antidiabetic, anti-obesity, anti-hyperlipidemic, and anticancer activities. M. nigra also showed protective effects against various human organs and systems, mainly based on its antioxidant capacity. These findings strongly suggest that M. nigra can be used as a promising nutraceutical resource to control and prevent various chronic diseases.
System based on subject-specific bands to recognize pedaling motor imagery: towards a BCI for lower-limb rehabilitation

Objective. The aim of this study is to propose a recognition system of pedaling motor imagery for lower-limb rehabilitation, which uses unsupervised methods to improve the feature extraction, and consequently the class discrimination of EEG patterns. Approach. After applying a spectrogram based on short-time Fourier transform (SSTFT), both sparseness constraints and total power are used on the time-frequency representation to automatically locate the subject-specific bands that pack the highest power during pedaling motor imagery. The output frequency bands are employed in the recognition system to automatically adjust the cut-off frequency of a low-pass filter (Butterworth, 2nd order). Riemannian geometry is also used to extract spatial features, which are further analyzed through a fast version of neighborhood component analysis to increase the class separability. Main results. For ten healthy subjects, our recognition system based on subject-specific bands achieved mean accuracy of and mean Kappa of . Significance. Our approach can be used to obtain a low-cost robotic rehabilitation system based on motorized pedal, as pedaling exercises have shown great potential for improving the muscular performance of post-stroke survivors.