Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostaglandins in Superovulation Induced Bovine Follicles During the Preovulatory Period and Early Corpus Luteum

The aim of this study was to characterize the regulation pattern of prostaglandin family members namely prostaglandin F2alpha (PTGF), prostaglandin E2 (PTGE), their receptors (PTGFR, PTGER2, PTGER4), cyclooxygenase 2 (COX-2), PTGF synthase (PTGFS), and PTGE synthase (PTGES) in the bovine follicles during preovulatory period and early corpus luteum (CL). Ovaries containing preovulatory follicles or CL were collected by transvaginal ovariectomy (n = 5 cows/group), and the follicles were classified: (I) before GnRH treatment; (II) 4 h after GnRH; (III) 10 h after GnRH; (IV) 20 h after GnRH; (V) 25 h after GnRH, and (VI) 60 h after GnRH (early CL). In these samples, the concentrations of progesterone (P4), estradiol (E2), PTGF and PTGE were investigated in the follicular fluid (FF) by validated EIA. Relative mRNA abundance of genes encoding for prostaglandin receptors (PTGFR, PTGER2, PTGER4), COX-2, PTGFS and PTGES were quantified by RT-qPCR. The localization of COX-2 and PTGES were investigated by established immunohistochemistry in fixed follicular and CL tissue samples. The high E2 concentration in the FF of the follicle group before GnRH treatment (495.8 ng/ml) and during luteinizing hormone (LH) surge (4 h after GnRH, 574.36 ng/ml), is followed by a significant (P<0.05) downregulation afterwards with the lowest level during ovulation (25 h after GnRH, 53.11 ng/ml). In contrast the concentration of P4 was very low before LH surge (50.64 mg/ml) followed by a significant upregulation (P < 0.05) during ovulation (537.18 ng/ml). The mRNA expression of COX-2 increased significantely (P < 0.05) 4 h after GnRH and again 20 h after GnRH, followed by a significant decrease (P < 0.05) after ovulation (early CL). The mRNA of PTGFS in follicles before GnRH was high followed by a continuous and significant downregulation (P < 0.05) afterwards. In contrast, PTGES mRNA abundance increased significantely (P < 0.05) in follicles 20 h after GnRH treatment and remained high afterwards. The mRNA abundance of PTGFR, PTGER2, and PTGER4 in follicles before GnRH was high, followed by a continuous and significant down regulation afterwards and significant increase (P < 0.05) only after ovulation (early CL). The low concentration of PTGF (0.04 ng/ml) and PTGE (0.15 ng/ml) in FF before GnRH, increased continuously in follicle groups before ovulation and displayed a further significant and dramatic increase (P < 0.05) around ovulation (101.01 ng/ml, respectively, 484.21 ng/ml). Immunohistochemically, the granulosa cells showed an intensive signal for COX-2 and PTGES in follicles during preovulation and in granulosa-luteal cells of the early CL. In conclusion, our results indicate that the examined bovine prostaglandin family members are involved in the local mechanisms regulating final follicle maturation and ovulation during the folliculo-luteal transition and CL formation.
On the Role of Adenosine A2A Receptor Gene Transcriptional Regulation in Parkinson’s Disease

Adenosine A2A receptors (A2ARs) have attracted considerable attention as an important molecular target for the design of Parkinson’s disease (PD) therapeutic compounds. Here, we studied the transcriptional regulation of the A2AR gene in human peripheral blood mononuclear cells (PBMCs) obtained from PD patients and in the striatum of the well-validated, 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We report an increase in A2AR mRNA expression and protein levels in both human cells and mice striata, and in the latter we could also observe a consistent reduction in DNA methylation at gene promoter and an increase in histone H3 acetylation at lysine 9. Of particular relevance in clinical samples, we also observed higher levels in the receptor gene expression in younger subjects, as well as in those with less years from disease onset, and less severe disease according to clinical scores. In conclusion, the present findings provide further evidence of the relevant role of A2AR in PD and, based on the clinical data, highlight its potential role as disease biomarker for PD especially at the initial stages of disease development. Furthermore, our preclinical results also suggest selective epigenetic mechanisms targeting gene promoter as tool for the development of new treatments.
Comparison Between Manual and (Semi-)Automated Analyses of Esophageal Diaphragm Electromyography During Endurance Cycling in Patients With COPD

Background: Electrocardiogram (ECG) contamination is present in diaphragm electromyography (EMGdi) recordings. Obtaining EMGdi without ECG contamination is crucial for EMG amplitude analysis. Manually selecting EMGdi in between QRS complexes has been most commonly applied in recent years (manual method). We developed a semi-automated analysis method based on Least Mean Square Adaptive Filtering combined with a synchronously recorded separate ECG channel to remove ECG artifacts from the EMGdi signals. We hypothesized that this approach would shorten analysis duration and might minimize the potential for inter-rater disagreement. Aims: We aimed to evaluate agreement between the semi-automated method and the manual method and inter-rater reliability of the manual method. Methods: Electromyography signals of seven patients with COPD were recorded using an esophageal catheter during an exercise test on a cycle ergometer. Four patients subsequently participated in an inspiratory muscle training (IMT) program for 8 weeks. After IMT, the tests were repeated. EMGdi/EMGdiMax as obtained either manually by the two assessors or retrieved from the semi-automated method were compared. Results: Semi-automated EMGdi/EMGdiMax agreed well with values obtained by one of the two manual assessors (assessor 1) both at pre-intervention measurements (mean difference −0.5%, 95% CI: −19.6 to 18.6%) and for the pre/post IMT differences (mean difference 1.2%, 95% CI: −16.8 to 19.2%). Intra-class correlation coefficients between methods were 0.96 (95% CI: 0.94–0.97) at pre-intervention measurements and 0.78 (95% CI: 0.58–0.89) for pre/post IMT differences (both p < 0.001). EMGdi/EMGdiMax from assessor 2 was systematically lower than from assessor 1 and agreed less well with the semi-automated method both at pre-intervention measurements (mean difference: 9.3%, 95% CI: −11.4 to 29.9%) and for pre/post IMT differences (mean difference 7.0%, 95% CI: −20.4 to 34.4%). Analysis duration of the semi-automated method was significantly shorter (29 ± 9 min) than the manual method (82 ± 20 min, p < 0.001). Conclusion: The developed semi-automated method is more time efficient and will be less prone to inter-rater variability that was observed when applying the manual analysis method. It is, therefore, proposed as a new standard for objective EMGdi amplitude analyses in future studies.
Transcriptional Effects of Ozone and Impact on Airway Inflammation

Epidemiological and challenge studies in healthy subjects and in individuals with asthma highlight the health impact of environmental ozone even at levels considered safe. Acute ozone exposure in man results in sputum neutrophilia in 30% of subjects particularly young children, females, and those with ongoing cardiopulmonary disease. This may be associated with systemic inflammation although not in all cases. Chronic exposure amplifies these effects and can result in the formation of asthma-like symptoms and immunopathology. Asthmatic patients who respond to ozone (responders) induce a greater number of genes in bronchoalveolar (BAL) macrophages than healthy responders with up-regulation of inflammatory and immune pathways under the control of cytokines and chemokines and the enhanced expression of remodeling and repair programmes including those associated with protease imbalances and cell-cell adhesion. These pathways are under the control of several key transcription regulatory factors including nuclear factor (NF)-κB, anti-oxidant factors such as nuclear factor (erythroid-derived 2)-like 2 NRF2, the p38 mitogen activated protein kinase (MAPK), and priming of the immune system by up-regulating toll-like receptor (TLR) expression. Murine and cellular models of acute and chronic ozone exposure recapitulate the inflammatory effects seen in humans and enable the elucidation of key transcriptional pathways. These studies emphasize the importance of distinct transcriptional networks in driving the detrimental effects of ozone. Studies indicate the critical role of mediators including IL-1, IL-17, and IL-33 in driving ozone effects on airway inflammation, remodeling and hyperresponsiveness. Transcription analysis and proof of mechanisms studies will enable the development of drugs to ameliorate the effects of ozone exposure in susceptible individuals.
Can the Attention Training Technique Reduce Stress in Students? A Controlled Study of Stress Appraisals and Meta-Worry

The present study tested the impact of attention training on cognition; secondary appraisal of perceived stress, and on metacognition; meta-worry in stressed students. Theoretically derived from the Self-Regulatory Executive Function model (S-REF model; Wells and Matthews, 1994a, 1996), the attention training technique (ATT; Wells, 1990) is intended to promote flexible, voluntary external attention and has been shown to reduce symptoms of psychological distress. The present experimental study explored the effects of ATT on cognitive and metacognitive levels of appraisal, namely perceived stress (primary outcome) and meta-worry (secondary outcome). Stressed students were randomized to an experimental ATT group (n = 23) or a control group (n = 23). The ATT group attended an initial training session followed by 4 weeks of individual (12 min) daily ATT practice. The control group waited for 4 weeks before receiving the intervention. The outcomes were scores on the Perceived Stress Scale 14 (PSS-14) and the Meta-Worry Questionnaire (MWQ) frequency and belief subscales at post study. Both measures decreased significantly following ATT with large pre- to post- effect sizes but there were minimal changes in the control group. The between-group differences were statistically significant. The results add to the literature on the potential effects of ATT by demonstrating effects on the content of cognitive stress appraisals and on meta-worry in an academic setting in a stressed student sample.
Variability in Genomic and Virulent Properties of Porphyromonas gingivalis Strains Isolated From Healthy and Severe Chronic Periodontitis Individuals

Porphyromonas gingivalis has been extensively associated with both the onset and progression of periodontitis. We previously isolated and characterized two P. gingivalis strains, one from a patient exhibiting severe chronic periodontitis (CP3) and another from a periodontally healthy individual (H3). We previously showed that CP3 and H3 exhibit differences in virulence since H3 showed a lower resistance to cationic peptides compared with CP3, and a lower ability to induce proliferation in gingival epithelial cells. Here, we aimed to determine whether differences in virulence between these two strains are associated with the presence or absence of specific genes encoding virulence factors. We sequenced the whole genomes of both P. gingivalis CP3 and H3 and conducted a comparative analysis regarding P. gingivalis virulence genetic determinants. To do so, we performed a homology search of predicted protein sequences in CP3 and H3 genomes against the most characterized virulence genes for P. gingivalis available in the literature. In addition, we performed a genomic comparison of CP3 and H3 with all the 62 genomes of P. gingivalis found in NCBI's RefSeq database. This approach allowed us to determine the evolutionary relationships of CP3 and H3 with other virulent and avirulent strains; and additionally, to detect variability in presence/absence of virulence genes among P. gingivalis genomes. Our results show genetic variability in the hemagglutinin genes. While CP3 possesses one copy of hagA and two of hagC, H3 has no hagA and only one copy of hagC. Experimentally, this finding is related to lower in vitro hemmaglutination ability of H3 compared to CP3. Moreover, while CP3 encodes a gene for a major fimbrium subunit FimA type 4 (CP3_00160), H3 possess a FimA type 1 (H3_01400). Such genetic differences are in agreement with both lower biofilm formation ability and less intracellular invasion to oral epithelial cells exhibited by H3, compared with the virulent strain CP3. Therefore, here we provide new results on the genome sequences, comparative genomics analyses, and phenotypic analyses of two P. gingivalis strains. The genomics comparison of these two strains with the other 62 genomes included in the analysis provided relevant results regarding genetic determinants and their association with P. gingivalis virulence.
Phα1β Spider Toxin Reverses Glial Structural Plasticity Upon Peripheral Inflammation

The incoming signals from injured sensory neurons upon peripheral inflammation are processed in the dorsal horn of spinal cord, where glial cells accumulate and play a critical role in initiating allodynia (increased pain in response to light-touch). However, how painful stimuli in the periphery engage glial reactivity in the spinal cord remains unclear. Here, we found that a hind paw inflammation induced by CFA produces robust morphological changes in spinal astrocytes and microglia compatible with the reactive phenotype. Strikingly, we discovered that a single intrathecal injection with venom peptides that inhibit calcium channels reversed all the glial pathological features of the peripheral inflammation. These effects were more apparent in rats treated with the Phα1β spider toxin (non-specific calcium channel antagonist) than ω-MVIIA cone snail toxin (selective N-type calcium channel antagonist). These data reveal for the first time a venom peptide acting on glial structural remodeling in vivo. We, therefore, suggest that calcium-dependent plasticity is an essential trigger for glial cells to initiate reactivity, which may represent a new target for the antinociceptive effects of Phα1β and ω-MVIIA toxins in inflammatory pain conditions.
Social Support and Emotional Intelligence as Protective Resources for Well-Being in Moroccan Adolescents

This study aimed to test a structural model to examine the protective role of psychosocial variables, such as social support, emotional intelligence and their interaction, on the cognitive dimension of subjective positive well-being (life satisfaction) and negative well-being (depression) in Moroccan adolescents. The participants consisted of 1277 students (571 men, 694 women and 12 missing values) with a mean age of 16.15 years (SD = 2.22; range = 9 to 23) who attended 26 public schools in different territories of Morocco. These students were in secondary education (n = 893) and high school (n = 378) (6 missing values). The scales for measuring the variables of interest had to be adapted and validated as a previous step for the further proposal of a model of relations. Statistical analyses were conducted using structural equation modeling (SEM) to test the proposed model. The model that optimally adjusted the data confirmed the protective role of social support in the well-being of Moroccan adolescents. Consistent with previous studies, social support was directly related to well-being. However, it also modulated levels of satisfaction with life. Likewise, the inclusion of emotional intelligence as an additional protective factor contributed to the explanation of the well-being mechanisms in adolescents. In addition to direct associations with the levels of social support, satisfaction with life and depression (negative in the latter case), emotional intelligence participated in a complex chain affecting life satisfaction and life satisfaction affecting depression. Moreover, the interaction of emotional intelligence with social support was confirmed to determine levels of life satisfaction in adolescents. Specifically, social support multiplied the effects of the relationship between satisfaction with life and emotional intelligence in cases of moderate and high levels in Moroccan adolescents. This study fills a gap in the literature by adapting and further analyzing several scales with Moroccan samples of adolescents and by proposing and verifying a relational model that can help researchers and teachers to more precisely clarify these relations according to their context. The enhancement of protective factors, such as social support and emotional intelligence, will promote healthy youth development, thus creating healthier societies in the future.
Tissue-Specific Orchestration of Gilthead Sea Bream Resilience to Hypoxia and High Stocking Density

Two different O2 levels (normoxia: 75–85% O2 saturation; moderate hypoxia: 42–43% O2 saturation) and stocking densities (LD: 9.5, and HD: 19 kg/m3) were assessed on gilthead sea bream (Sparus aurata) in a 3-week feeding trial. Reduced O2 availability had a negative impact on feed intake and growth rates, which was exacerbated by HD despite of the improvement in feed efficiency. Blood physiological hallmarks disclosed the enhancement in O2-carrying capacity in fish maintained under moderate hypoxia. This feature was related to a hypo-metabolic state to cope with a chronic and widespread environmental O2 reduction, which was accompanied by a differential regulation of circulating cortisol and growth hormone levels. Customized PCR-arrays were used for the simultaneous gene expression profiling of 34–44 selected stress and metabolic markers in liver, white skeletal muscle, heart, and blood cells. The number of differentially expressed genes ranged between 22 and 19 in liver, heart, and white skeletal muscle to 5 in total blood cells. Partial Least-Squares Discriminant Analysis (PLS-DA) explained [R2Y(cum)] and predicted [Q2Y(cum)] up to 95 and 65% of total variance, respectively. The first component (R2Y = 0.2889) gathered fish on the basis of O2 availability, and liver and cardiac genes on the category of energy sensing and oxidative metabolism (cs, hif-1α, pgc1α, pgc1β, sirts 1-2-4-5-6-7), antioxidant defense and tissue repair (prdx5, sod2, mortalin, gpx4, gr, grp-170, and prdx3) and oxidative phosphorylation (nd2, nd5, and coxi) highly contributed to this separation. The second component (R2Y = 0.2927) differentiated normoxic fish at different stocking densities, and the white muscle clearly promoted this separation by a high over-representation of genes related to GH/IGF system (ghr-i, igfbp6b, igfbp5b, insr, igfbp3, and igf-i). The third component (R2Y = 0.2542) discriminated the effect of stocking density in fish exposed to moderate hypoxia by means of hepatic fatty acid desaturases (fads2, scd1a, and scd1b) and muscle markers of fatty acid oxidation (cpt1a). All these findings disclose the different contribution of analyzed tissues (liver ≥ heart > muscle > blood) and specific genes to the hypoxic- and crowding stress-mediated responses. This study will contribute to better explain and understand the different stress resilience of farmed fish across individuals and species.
Functional Connectivity Within the Gustatory Network Is Altered by Fat Content and Oral Fat Sensitivity – A Pilot Study

Background: The amount of fat in ingested food dictates specific activation patterns in the brain, particularly in homeostatic and reward-related areas. Taste-specific brain activation changes have also been shown and the sensitivity to the oral perception of fat is associated with differential eating behavior and physiological parameters. The association between oral fat sensitivity and neuronal network functions has, however, not yet been defined. Objective: We aimed to investigate the association between fat-dependent neuronal functional connectivity patterns and oral fat sensitivity. Design: To investigate the underlying changes in network dynamics caused by fat intake, we measured resting-state functional connectivity in 11 normal-weight male participants before and after a high- vs. a low-fat meal on two separate study days. Oral fat sensitivity was also measured on both days. We used a high-resolution functional magnetic resonance imaging (MRI) sequence to measure any connectivity changes in networks with the seed in the brainstem (nucleus tractus solitarii, NTS), in homeostatic (hypothalamus) and in reward regions (ventral and dorsal striatum). Seed-based functional connectivity (FC) maps were analyzed using factorial analyses and correlation analyses with oral fat sensitivity were also performed. Results: Regardless of fat content, FC between NTS and reward and gustatory areas was lower after ingestion. Oral fat sensitivity was positively correlated with FC between homeostatic regions and limbic areas in the high-fat condition, but negatively correlated with FC between the dorsal striatum and somatosensory regions in the low-fat condition. Conclusion: Our results show the interaction of oral fat sensitivity with the network based neuronal processing of high- vs. low-fat meals. Variations in neuronal connectivity network patterns might therefore be a possible moderator of the association of oral fat sensitivity and eating behavior.
Integrated receiver channel circuits and structures for a pulsed time-of-flight laser radar

This thesis describes the development of integrated structures and circuit implementations for the receiver channel of portable pulsed time-of-flight laser rangefinders for industrial measurement applications where the measurement range is from ~ 1 m to ~ 100 m to noncooperative targets and the required measurement accuracy is from a few millimetres to a few centimetres. The receiver channel is used to convert the current pulse from a photodetector to a voltage pulse, amplify it, discriminate the timing point and produce an accurately timed logic-level pulse for a time-to-digital converter. Since the length of the laser pulse, typically 5 ns, is large compared to the required accuracy, a specific point in the pulses has to be discriminated. The amplitude of the input pulses varies widely as a function of measurement range and the reflectivity of the target, typically from 1 to 100 . 1000, so that the gain of the amplifier channel needs to be controlled and the discrimination scheme should be insensitive to the amplitude variation of the input signal. Furthermore, the amplifier channel should have low noise in order to minimize timing jitter. Alternative circuit structures are discussed, the treatment concentrating on the preamplifier, gain control circuitry and timing discriminator, which are the key circuit blocks from the performance point of view. New circuit techniques and structures, such as a fully differential transimpedance preamplifier and a current mode gain control scheme, have been developed. Several circuit implementations for different applications are presented together with experimental results, one of them being a differential BiCMOS receiver channel with a bandwidth of 170 MHz, input referred noise of 6 pA/ and maximum transimpedance of 260 kΩ. It has an accuracy of about +/7 mm (average of 10000 measurements), taking into account walk error with an input signal range of 1:624 and jitter (3σ). The achievable performance level using integrated circuit technology is comparable or superior to that of the previously developed commercially available discrete component implementations, and the significantly reduced size and power consumption open up new application areas.