Miracle-dz/UniFAR-FTUs huggingface dataset:
Short- and Long-Term Regulation of Adenylyl Cyclase Activity by δ-Opioid Receptor Are Mediated by Gαi2 in Neuroblastoma N2A Cells

Activation of the opioid receptor results in short-term inhibition of intracellular cAMP levels followed by receptor desensitization and subsequent increase of cAMP above the control level (adenylyl cyclase superactivation). Using adenovirus to deliver pertussis toxin-insensitive mutants of the α-subunits of Gi/o that are expressed in neuroblastoma Neuro2A cells (Gαi2, Gαi3, and Gαo), we examined the identities of the G proteins involved in the short- and long-term action of the δ-opioid receptor (DOR). Pertussis toxin pretreatment completely abolished the ability of [d-Pen2, d-Pen5]-enkephalin (DPDPE) to inhibit forskolin-stimulated intracellular cAMP production. Expression of the C352L mutant of Gαi2, and not the C351L mutants of Gαi3 or Gαo, rescued the short-term effect of DPDPE after pertussis toxin treatment. The ability of Gαi2 in mediating DOR inhibition of adenylyl cyclase activity was also reflected in the ability of Gαi2, not Gαi3 or Gαo, to coimmunoprecipitate with DOR. Coincidently, after long-term DPDPE treatment, pertussis toxin treatment eliminated the antagonist naloxone-induced superactivation of adenylyl cyclase activity. Again, only the C352L mutant of Gαi2 restored the adenylyl cyclase superactivation after pertussis toxin treatment. More importantly, the C352L mutant of Gαi2 remained associated with DOR after long-term agonist and pertussis toxin treatment whereas the wild-type Gαi2 did not. These data suggest that Gαi2 serves as the signaling molecule in both DOR-mediated short- and long-term regulation of adenylyl cyclase activity.
Complex Interactions between Genes and Social Environment Cause Phenotypes Associated with Autism Spectrum Disorders in Mice

Abstract The etiology of autism spectrum disorders (ASDs) is a complex combination of genetic and environmental factors. Neuroligin3, a synaptic adhesion protein, and cytoplasmic FMR1 interacting protein 1 (CYFIP1), a regulator of protein translation and actin polymerization, are two proteins associated with ASDs that interact in neurons in vivo. Here, we investigated the role of the Neuroligin3/CYFIP1 pathway in behavioral functioning and synapse formation in mice and found that it contributes to motor learning and synapse formation in males. Similar investigation in female mice revealed an absence of such phenotypes, suggesting that females are protected against mutations affecting this pathway. Previously, we showed that the social environment influences the behavior of male mice. We extended this finding and found that the transcriptome of wild-type mice housed with their mutant littermates, lacking Neuroligin3, differed from the transcriptome of wild-type mice housed together. Altogether, these results identify the role of the Neuroligin3/CYFIP1 pathway in male mouse behavior and highlight its sensitivity to social environment.
cysA, cysP, and rpoS mutations increase the power density in P. aeruginosa microbial fuel cells: Performing enhancement based on metabolic flux analysis

This study presents the simulation of a MFC with Pseudomonas aeruginosa based on a metabolic flux analysis (MFA) which arises as a linear programming model that served as input for the fuel cell model. The linear model was implemented in Xpress MP? and the coupling model in Comsol Multiphysics? The in silico model predicted maximum potentials of 0.135 V which were consistent with those obtained in the experimental cell. Afterwards, an optimization platform based on multiobjective optimization approach was implemented aimed to determine genes that increase the average cell power. cysA, cysP and rpoS mutants which were predicted to increase the power of the cell, were experimentally tested with an air cathode fuel cell finding an augment up to 35-fold in the average power density for the rpoS mutant. Power densities were obtained through experimentation in the range of [0.13 - 5] mW/m2. Electron shuttle rise was qualitative corroborated trough cyclic voltammetry tests, which allowed to visualize the augment of the peaks for rpoS mutation.
Global change and agro-forest ecosystems: Adaptation and mitigation in a FACE experiment on a poplar plantation

Abstract The objective of this research was to determine the functional responses of a cultivated, agro-forestry system, namely a poplar plantation, to actual and future atmospheric CO2 concentrations. Hence, this research has combined a fast growing, agro-forestry ecosystem, capable of elevated biomass production, with a large-scale Free Air Carbon Enrichment (FACE) system, one of the few available in the European Union on a forest tree stand. The FACE facility is located close to a natural CO2 source and is drawing scientists from several European countries, and from other continents, to closely cooperate and combine their scientific efforts on the same experimental system. Furthermore, this FACE apparatus utilizes a novel technology, originally developed by Italian institutions, based on the release into the atmosphere, at sonic velocity, of pure CO2 instead of an air-CO2 mixture. The research activities conducted at the POPFACE site, on the responses of the tree plantation to future atmospheric conditions, have integrated observations at the leaf level, such as photosynthesis, respiration and transpiration, with measures carried out at the whole-tree and stand scale, such as canopy architecture, light interception and biomass production. Finally, the ecosystem dimension has also been analysed by studying root productivity and soil processes, host – parasite interactions, and carbon sequestration throughout a rotation cycle of the stand.
Depressive symptoms, parental stress, and attachment style in mothers and fathers two and a half years after childbirth: Are fathers as affected as mothers?

The study aimed to determine the prevalence of depressive symptoms and whether parental stress and attachment style affected depression in mothers and fathers two and a half years after the birth of a child. The parents completed several questionnaires including the Edinburgh Postnatal Depression Scale, the Swedish Parenthood Stress Questionnaire and the Relationship Questionnaire. The prevalence rate of depressive symptoms in mothers was 14.9%, while for fathers it was 11.5%. Differences between the parents identified as depressed and those without depressive symptoms were also analysed. There were no significant differences between depressed and non-depressed parents on the secure, avoidant and fearful attachment styles. However, there was a significant difference between groups on the preoccupied subscale. The final aim was to calculate if attachment style contributed to the level of depression while accounting for the impact of parental stress. Parental stress (incompetence, social isolation and spouse relationship problems) was the best predictor for mothers’ depressive symptoms, while parental stress (social isolation and health) and the preoccupied attachment style were the best predictors for such symptoms in fathers. The findings indicated that parental stress and depressive symptoms are closely related and can explain the difficulties parents face.
Pain perception in chronic knee osteoarthritis with varying levels of pain inhibitory control: an exploratory study

Abstract Background and aims Pain is a disabling symptom in knee osteoarthritis (KOA) and its underlying mechanism remains poorly understood. Dysfunction of descending pain modulatory pathways and reduced pain inhibition enhance pain facilitation in many chronic pain syndromes but do not fully explain pain levels in chronic musculoskeletal conditions. The objective of this study is to explore the association of clinical variables with pain intensity perception in KOA individuals with varying levels of Conditioned Pain Modulation (CPM) response. Methods This is a cross-sectional, exploratory analysis using baseline data of a randomized clinical trial investigating the effects of a non-invasive brain stimulation treatment on the perception of pain and functional limitations due to KOA. Sixty-three subjects with KOA were included in this study. Data on pain perception, mood perception, self-reported depression, physical function, quality of life, and quantitative sensory testing was collected. Multiple linear regression analysis was performed to explore the association between the clinical variables with pain perception for individuals with different levels of CPM response. Results For KOA patients with limited CPM response, perception of limitations at work/other activities due to emotional problems and stress scores were statistically significantly associated with pain scores, F(2, 37) = 7.02, p < 0.01. R-squared = 0.275. For KOA patients with normal CPM response, general health perception scores were statistically significantly associated with pain scores, F(1, 21) = 5.60, p < 0.05. R-squared = 0.2104. Limitations of this study include methodology details, small sample size and study design characteristics. Conclusions Pain intensity perception is associated differently with clinical variables according to the individual CPM response. Mechanistic models to explain pain perception in these two subgroups of KOA subjects are discussed.
Extended-spectrum β-lactamases and the permeability barrier

The outer membrane of Gram-negative bacteria represents a barrier for penetration of hydrophilic compounds. Loss of porins (water-filled protein channels) contributes to antimicrobial resistance, particularly when additional mechanisms of resistance are expressed. Many studies on the structure and regulation of porins in Escherichia coli K-12 are available, but there is little information concerning clinical isolates of this species. In Klebsiella pneumoniae, two major porins, OmpK35 and OmpK36, are produced, but many extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae isolates do not express OmpK35. Loss of both OmpK35 and OmpK36 in ESBL-producing K. pneumoniae causes resistance to cefoxitin, increased resistance to expanded-spectrum cephalosporins, and decreased susceptibility to carbapenems, particularly ertapenem. Porin loss also decreases the susceptibility to other non-beta-lactam compounds, such as fluoroquinolones, of ESBL-producing organisms.
Role for Interleukin-1β in Trypanosoma cruzi-Induced Cardiomyocyte Hypertrophy

ABSTRACT Chagas' disease, the leading cause of heart failure in Latin America, results from infection with the intracellular protozoan parasite Trypanosoma cruzi. Host cell responses elicited in the myocardium early in the infective process are thought to be critical for establishment of infection by this pathogen; however, these changes have not been well characterized. We report here that primary cardiomyocytes undergo hypertrophy as an early response to T. cruzi infection. The T. cruzi-elicited hypertrophic response is characterized by increased expression of genes encoding the contractile proteins MyHCβ and MyHCα, followed by an approximately twofold increase in cell size. Hypertrophy was observed in both parasite-containing and noninfected cell populations represented in T. cruzi-infected cultures, indicating the involvement of a soluble mediator in this process. Conditioned medium harvested from T. cruzi-infected cultures, which contained significant levels of interleukin-1β (IL-1β) but not endothelin-1 or tumor necrosis factor alpha, was sufficient to induce hypertrophy in isolated cardiomyocytes. Addition of a high-affinity receptor chimera, IL-1 trap, to cardiomyocyte cultures blocked the overall increase in cell size elicited by T. cruzi. These novel findings indicate that IL-1β, which is rapidly induced in response to T. cruzi, promotes cardiomyocyte hypertrophy early in the infective process and may contribute to maintenance of cardiomyocyte function during establishment of T. cruzi infection in the heart.
Forcecardiography: A Novel Technique to Measure Heart Mechanical Vibrations onto the Chest Wall

This paper presents forcecardiography (FCG), a novel technique to measure local, cardiac-induced vibrations onto the chest wall. Since the 19th century, several techniques have been proposed to detect the mechanical vibrations caused by cardiovascular activity, the great part of which was abandoned due to the cumbersome instrumentation involved. The recent availability of unobtrusive sensors rejuvenated the research field with the most currently established technique being seismocardiography (SCG). SCG is performed by placing accelerometers onto the subject’s chest and provides information on major events of the cardiac cycle. The proposed FCG measures the cardiac-induced vibrations via force sensors placed onto the subject’s chest and provides signals with a richer informational content as compared to SCG. The two techniques were compared by analysing simultaneous recordings acquired by means of a force sensor, an accelerometer and an electrocardiograph (ECG). The force sensor and the accelerometer were rigidly fixed to each other and fastened onto the xiphoid process with a belt. The high-frequency (HF) components of FCG and SCG were highly comparable (r > 0.95) although lagged. The lag was estimated by cross-correlation and resulted in about tens of milliseconds. An additional, large, low-frequency (LF) component, associated with ventricular volume variations, was observed in FCG, while not being visible in SCG. The encouraging results of this feasibility study suggest that FCG is not only able to acquire similar information as SCG, but it also provides additional information on ventricular contraction. Further analyses are foreseen to confirm the advantages of FCG as a technique to improve the scope and significance of pervasive cardiac monitoring.
Serum Matrix Metalloproteinases and Left Atrial Remodeling—The Hoorn Study

Extracellular matrix protein turnover may play an important role in left atrial (LA) remodelling. The aim is to investigate the associations between matrix metalloproteinase (MMPs), tissue inhibitor of metalloproteinase (TIMP-1) and LA volume index (LAVI) and if these associations are independent of TIMP-1 levels. Participants from The Hoorn Study, a population-based cohort study (n = 674), underwent echocardiography. Serum MMPs (i.e., MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10) and TIMP-1 levels were measured with ELISA. Multiple linear regression analyses were used. MMP-1 levels were not associated with LAVI. Higher MMP-2 levels were associated with larger LAVI (regression coefficient per SD increase in MMP (95% CI); 0.03 (0.01; 0.05). Higher MMP-3 and MMP-9 levels were associated with smaller LAVI; −0.04 (−0.07; −0.01) and −0.04 (−0.06; −0.02) respectively. Only in women were higher MMP-10 levels associated with larger LAVI; 0.04 (0.00; 0.07, p-interaction 0.04). Additionally, only in women were higher TIMP-1 levels associated with smaller LAVI; −0.05 (−0.09; −0.01, p-interaction 0.03). The associations between MMPs and LAVI were independent of TIMP-1 levels. In conclusion, serum MMPs are associated with LAVI, independent of CVD risk factors and TIMP-1 levels. In addition, these associations differ according to sex and within MMP subgroups. This shows that the role of MMPs in LA remodelling is complex.
Recent Stereological Methods for the Measurement of Leaf Anatomical Characteristics: Estimation of Volume Density, Volume and Surface Area

Recent design-based stereological methods for the measurement of the proportion of mesophyll in the leaf, the proportion of intercellular spaces in the mesophyll, the leaf volume, the mesophyll volume. and the exposed leaf surface area of mesophyll are described in an easy-to-follow manner. Two leaf types are considered: grass leaf and bifacial leaf. The presented methods are discussed and compared with alternative methods
Who were the Hyksos? Challenging traditional narratives using strontium isotope (87Sr/86Sr) analysis of human remains from ancient Egypt

A foreign dynasty, known as the Hyksos, ruled parts of Egypt between c. 1638–1530 BCE. Their origins are thought to be rooted in the Near East, which is supported by architectural features and grave accoutrements of Tell el-Dabca. In this former Hyksos capital in the Eastern Nile Delta, burial culture is characterized by a blend of Egyptian and Near Eastern elements. However, investigations are still ongoing as to where the Hyksos came from and how they rose to power. The aim of this study is to elucidate the question of possible provenience. We present the results of strontium isotope (87Sr/86Sr) ratios of human tooth enamel (n = 75) from Tell el-Dabca, focusing on comparing pre- and during Hyksos rule and sex-based differences. An influx of non-locals can be observed in the pre-Hyksos period (12th and 13th Dynasties, c. 1991–1649 BCE) during the constitution of this important harbor town, while the number of individuals already born in the Delta is larger during the Hyksos period. This is consistent with the supposition that, while the ruling class had Near Eastern origins, the Hyksos’ rise to power was not the result of an invasion, as popularly theorized, but an internal dominance and takeover of foreign elite. There is a preponderance of non-local females suggesting patrilocal residence. We discuss our findings against the current evidence of material culture and historiography, but more investigation in Near Eastern comparative sites has to be conducted to narrow our future search for the actual origins of the Hyksos.
Efeito de programas de restrição alimentar sobre o desempenho produtivo e econômico e a deposição de gordura na carcaça de frangos de corte

O objetivo deste trabalho foi avaliar, aos 42 dias de idade, o desempenho produtivo e economico e os rendimentos de carcaca e cortes nobres, em frangos de corte submetidos a diferentes programas de restricao alimentar quantitativa, aplicada em idade precoce. Foi usado delineamento inteiramente casualizado, em esquema fatorial 5x2 (programa de restricao alimentar versus sexo) e cinco repeticoes com 20 aves por unidade experimental. O consumo de racao e ganho de peso foram reduzidos pelos programas de restricao alimentar, porem a conversao alimentar nao foi influenciada. Os rendimentos de carcaca e cortes nobres e os teores de gordura abdominal nao foram influenciados pelos programas de restricao alimentar. Os resultados economicos mostraram que a restricao alimentar e indicada, principalmente, quando os custos das racoes estao elevados e o preco do frango e baixo no mercado produtor.
Thiopurines’ Metabolites and Drug Toxicity: A Meta-Analysis

Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines’ metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines’ metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD −40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = −0.21), neutrophils (r = −0.24) and alanine aminotransferase levels (r = −0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95% CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95% CI 3.20; 5.71). Levels of 6-MMPR measured in the first 8 weeks of treatment were associated with leukopenia. We conclude that TDM could be used to prevent thiopurines’ toxicity. As optimal metabolites level may vary according to indication, physicians may adapt posology to decrease toxicity without compromising efficacy.
Left Ventricular Filling Characteristics in Mild Untreated Hypertension

To determine the transmitral blood flow characteristics in mild hypertension, Doppler and standard echocardiography were prospectivel performed in 37 patients with untreated mild hypertension (152 ± 16/98 ± 5 mm Hg ± SD) and 23 normotensive controls (122 ± 9/76 ± 7 mm Hg). Left atrial emptying index, relaxation time index, left ventricular mass, and left ventricular systolic function were derived by standard echocardiographic methods. Doppler transmitral peak velocity E and peak velocity A were determined, and the ratio A/E was calculated. Since A/E is positively correlated with age, the ratio was further adjusted by dividing by age (A/E/Age). The A/E ratio (p = 0.001), the A/E/Age ratio (p = 0.001), left ventricular mass (p = 0.005), and relaxation time index (p = 0.001) were all significantly higher, whereas the left atrial emptying index was significantly lower (p = 0.001), in the hypertensive subjects when compared with the controls. These differences persisted even when the two groups were matched for left ventricular mass. In the hypertensive patients, no correlation was observed between the A/E ratio and systolic, diastolic, or mean blood pressure or left ventricular mass. In the hypertensive patients, the A/E ratio did correlate with both the atrial emptying index and the relaxation time index. From these data we conclude that 1) transmitral blood flow might be abnormal in patients with mild, untreated hypertension even before an increase in left ventricular mass and 2) in the hypertensive subjects, the lack of correlation between transmitral blood flow velocity and blood pressure suggests that pathophysiologlcal factors other than blood pressure elevation alone contribute to the development of these diastolic filling abnormalities.
Improved balance in middle-aged adults after 8 weeks of a modified version of Otago Exercise Program: A randomized controlled trial

Objective The objective of this randomized controlled trial was to examine dynamic balance changes (reach distance) in middle-aged adults using the Y Balance Test (YBT) following 8 weeks of home-based exercise program adapted from the Otago Exercise Program (OEP). Methods Fifty-two healthy middle-aged adults with mean age of 54.4±5.4 years and body mass index of 27.7±5.7 kg/m2 were randomly assigned into either the exercise group (a modification of the Otago Exercise Program, that consisted of home-based balance and strength exercises) or the non-exercise group (continuation of usual lifestyle) by having the participants select a paper from a sealed envelope. The YBT was used to measure participants’ dynamic balance in the right and left anterior (RA, LA), posteromedial (RPM, LPM), and posterolateral (RPL, LPL) directions. Results The outcome in this trial was reach distance (cm). There was a significant group by time interaction in terms of reach distance for all directions (p<0.05, η2 ranged from 0.06 to 0.20). In the exercise group, results of the repeated measures analysis of variance (ANOVA) showed significant improvements in the reach distance in all the directions (p<0.001). In contrast, the non-exercise group had significant difference only in the left posterolateral direction (p = 0.009). Participants in the exercise group achieved significantly greater reach distance (cm) (95% confidence interval (CI)) for RA[(2.8, 0.4 to 5.2), p = 0.023]; LA[(3.2, 0.9 to 5.6), p = 0.008]; RPM[(4.0, 1.0 to 7.9), p = 0.046]; LPM[(5.8,1.3 to 10.3), p = 0.013]; RPL[(7.6, 2.6 to 12.6), p = 0.003]; and LPL[(4.2, 0.3 to 8.2), p = 0.035]. Conclusion The modified version of OEP appears to be effective in improving parameters of dynamic balance in the middle-aged adult population. The improvements in YBT reach distance in the exercise group are indicative of the significance of performing balance and strength exercises regularly for this population.