Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of dopaminergic cell degeneration on electrophysiological characteristics and GAD65/GAD67 expression in the substantia nigra: Different action on GABA cell subpopulations

The motor disturbances occurring in Parkinson's disease have been partially attributed to a hyperactivity of γ‐aminobutyric acid (GABA) ‐ergic nigral cells largely in the substantia nigra pars reticulata (SNr) secondary to the degeneration of dopaminergic nigrostriatal neurons. However, some aspects of this response remain unclear. In this work, different electrophysiological and neurochemical parameters were studied in GABAergic cells of the SN after unilateral nigrostriatal dopaminergic lesion using 6‐hydroxydopamine injection in rats. Our data showed that 1) the SN under normal conditions contains different subsets of GABAergic cells according to their firing pattern and glutamic acid decarboxylase mRNA levels, and 2) the response of these GABAergic cell subgroups was different after the ipsi‐ and contralateral dopaminergic cell degeneration. These findings indicate a complex regulation of nigral GABAergic activity after nigrostriatal dopaminergic degeneration that probably involves local mechanisms, the nigro‐striato‐nigral loop, as well as interhemispheric mechanisms whose anatomical basis remains unstudied. © 2002 Movement Disorder Society
Dihydrotetrabenazine Binding and Monoamine Uptake in Mouse Brain Regions

Abstract: Binding of [2‐3H]dihydrotetrabenazine and uptake of 5‐hydroxytryptamine (serotonin) were studied in mouse brain cerebellum, pons‐medulla, frontal cortex, hypothalamus, hippocampus, and striatum. Binding of [2‐3H]dihydrotetrabenazine to homogenates of these brain areas is stable for several hours and occurs at a homogeneous class of binding sites (KD= 2.4 nM). Subcellular fractionation and regional distribution of [2‐3H]dihydrotetrabenazine binding and serotonin uptake showed that the ligand binds to synaptic vesicles. Dihydrotetrabenazine inhibited serotonin uptake with the same inhibitory constant (IC50= 2.6 nM) for synaptic vesicles from brain regions containing 3,4‐dihydroxy‐phenylethylamine (dopamine) or serotonin and noradrenaline in different proportions. This constant is similar to the KD of [2‐3H]dihydrotetrabenazine, which suggests that the latter ligand labels specifically and with the same affinity the monoamine transporter from various mono aminergic synaptic vesicles. Therefore the regional differences in central monoamine depletion induced in vivo by tetrabenazine are not due to regional differences in inhibition of vesicular monoamine uptake. Moreover, vesicular monoamine transporters from the central and peripheral nervous systems of various mammals and from bovine adrenal glands have comparable affinity for substrate and inhibitor (Km values for serotonin and IC50 for dihydrotetrabenazine are about 0.8 μM and 3 nM, respectively) and comparable turnover number (10–35 molecules transported per transporter per minute), which suggests the involvement of a common transporter molecule in the process of monoamine uptake by the various monoaminergic storage vesicles.
Distinguishing fibroblast promigratory and procontractile growth factor environments in 3‐D collagen matrices

Understanding growth factor function during wound repair is necessary for the development of therapeutic interventions to improve healing outcomes. In the current study, we compare the effects of serum and purified growth factors on human fibroblast function in three different collagen matrix models: cell migration in nested matrices, floating matrix contraction, and stressed‐released matrix contraction. The results of these studies indicate that platelet‐derived growth factor (PDGF) is unique in its capacity to promote cell migration. Serum, lysophosphatidic acid, sphingosine‐1‐phophate (S1P), and endothelin‐1 promote stressed‐released matrix contraction but not cell migration. In addition, we found that S1P inhibits fibroblast migration and treatment of serum to remove lipid growth factors or treatment of cells to interfere with S1P2 receptor function increases serum promigratory activity. Our findings suggest that different sets of growth factors generate promigratory and procontractile tissue environments for fibroblasts and that the balance between PDGF and S1P is a key determinant of fibroblast promigratory activity. —Jiang, H. , Rhee, S. , Ho, C. ‐H. , Grinnell, F. Distinguishing fibroblast promigratory and procontractile growth factor environments in 3‐D collagen matrices. FASEB J. 22, 2151–2160 (2008)
Morphological Changes Caused by Experimental Streptococcus uberis Mastitis in Mice following Intramammary Infusion of Pokeweed Mitogen

Abstract Mice were used as models for bovine mastitis in an attempt to modify the susceptibility of mammary glands to Streptococcus uberis infection. Murine mammary glands were injected with pokeweed mitogen (PWM) prior to experimental bacterial challenge to accelerate involution and enhance antimicrobial mechanisms. PWM injection reduced the numbers of streptococci recovered when compared to controls. Histological examination of tissues from PWM-treated mice revealed a reduction in secretory activity and advanced involution. PWM-treated tissues had considerably more leukocytes infiltrating the epithelium, lumen, and underlying connective tissue. Bacteria were observed within the epithelium and alveolar lumen and internalized within neutrophils and macrophages in both PWM-injected and control tissue. Results of this study suggest PWM injection provided some protection against S. uberis mastitis by accelerating mammary involution, enhancing antimicrobial defenses, and facilitating a marked cellular response prior to bacterial challenge.
Neural mechanisms underlying target detection in a dragonfly centrifugal neuron

SUMMARY Visual identification of targets is an important task for many animals searching for prey or conspecifics. Dragonflies utilize specialized optics in the dorsal acute zone, accompanied by higher-order visual neurons in the lobula complex, and descending neural pathways tuned to the motion of small targets. While recent studies describe the physiology of insect small target motion detector (STMD) neurons, little is known about the mechanisms that underlie their exquisite sensitivity to target motion. Lobula plate tangential cells (LPTCs), a group of neurons in dipteran flies selective for wide-field motion, have been shown to take input from local motion detectors consistent with the classic correlation model developed by Hassenstein and Reichardt in the 1950s. We have tested the hypothesis that similar mechanisms underlie the response of dragonfly STMDs. We show that an anatomically characterized centrifugal STMD neuron (CSTMD1) gives responses that depend strongly on target contrast, a clear prediction of the correlation model. Target stimuli are more complex in spatiotemporal terms than the sinusoidal grating patterns used to study LPTCs, so we used a correlation-based computer model to predict response tuning to velocity and width of moving targets. We show that increasing target width in the direction of travel causes a shift in response tuning to higher velocities, consistent with our model. Finally, we show how the morphology of CSTMD1 allows for impressive spatial interactions when more than one target is present in the visual field.
Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation

Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPAR and incident HF and AF in a population‐based cohort.
Kefir-isolated Lactococcus lactis subsp. lactis inhibits the cytotoxic effect of Clostridium difficile in vitro

Kefir is a dairy product obtained by fermentation of milk with a complex microbial population and several health-promoting properties have been attributed to its consumption. In this work, we tested the ability of different kefir-isolated bacterial and yeast strains (Lactobacillus kefir, Lb. plantarum, Lactococcus lactis subps. lactis, Saccharomyces cerevisiae and Kluyveromyces marxianus) or a mixture of them (MM) to antagonise the cytopathic effect of toxins from Clostridium difficile (TcdA and TcdB). Cell detachment assays and F-actin network staining using Vero cell line were performed. Although incubation with microbial cells did not reduce the damage induced by C. difficile spent culture supernatant (SCS), Lc. lactis CIDCA 8221 and MM supernatants were able to inhibit the cytotoxicity of SCS to Vero cells. Fraction of Lc. lactis CIDCA 8221 supernatant containing components higher than 10 kDa were responsible for the inhibitory activity and heating of this fraction for 15 min at 100 °C completely abrogated this ability. By dot-blot assay with anti-TcdA or anti-TcdB antibodies, concentration of both toxins seems to be reduced in SCS treated with Lc. lactis CIDCA 8221 supernatant. However, protective effect was not affected by treatment with proteases or proteases-inhibitors tested. In conclusion, we demonstrated that kefir-isolated Lc. lactis CIDCA 8221 secreted heat-sensitive products able to protect eukaryotic cells from cytopathic effect of C. difficile toxins in vitro. Our findings provide new insights into the probiotic action of microorganisms isolated from kefir against virulence factors from intestinal pathogens.
Group A streptococcal infection in children younger than three years of age.

We evaluated 758 sick children younger than 3 years of age for Group A beta-hemolytic streptococcal (GABHS) upper respiratory infection (URI) to determine the usual clinical presentation of the disease in this age group, indications for culture and the optimal site(s) from which to isolate the organism. GABHS infection was documented in 35 subjects (4.6%). The classic presentation (as proposed in the 1940s) of GABHS URI in children younger than 3 years of age was not confirmed by this study. In 32 of the GABHS cases there were pharyngitis, common cold symptoms or both, and these were associated with acute otitis media 10 times and with otitis media with effusion 3 times. Clinical impetigo was associated with GABHS URI (4 of 32 cases). GABHS URI would not have been documented in 6 of 32 cases if cultures of the anterior nares had not been performed. Children between 18 and 36 months of age were more likely to have GABHS disease than were younger children. Hoarseness and vomiting occurred less frequently in children younger than 36 months with GABHS infection than in those of that age who had non-beta-hemolytic streptococcal illnesses. A history of two or more siblings at home or a family member with a recent streptococcal infection and the presence of irritability, a reddened throat or palate or uvular edema were each associated with GABHS URI. We concluded that sick children between 18 and 36 months of age with a reddened throat should have cultures taken of the throat and anterior nares for GABHS. (ABSTRACT TRUNCATED AT 250 WORDS)
[Stability of protein to digestion in vitro].

OBJECTIVE To establish test model of stability of different protein to digestion in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). METHODS The component of SGF and SIF being from the United States Pharmacopeia, the stability of various proteins were tested. The concentration of protein in SGF/SIF was 0.5mg/ml. At intervals of 0s, 15s, 30s, 60s, 2min, 4min, 8min, 15min, 30min and 60min, the samples were taken out. According to the results of SDS-PAGE, the stability of various proteins to digestion in SGF/SIF was observed. RESULTS The experiment showed that trypsin inhibitor from soybean, beta-lactoglobulin A from bovine milk and beta-lactoglobulin B from bovine milk were stable within 60min in SGF. Peanut lectin was digested within 8min. Most soybean lectin was digested within 8min, but the degraded fragments still existed. Ovalbumin, ovomucoid, BSA, soybean lipoxygenase and potato acid phosphatase were digested within 15s. The results in SGF were not consistent with the results in SIF. Trypsin inhibitor from soybean, beta lactoglobulin A from bovine milk, beta-lactoglobulin B from bovine milk, BSA, ovalbumin, ovomucoid, soybean lectin and peanut lectin were stable for 60min in SIF. The degraded fragments of soybean lipoxygenase and potato acid phospatase exited within 60min. CONCLUSION Different proteins showed different stability to SGF/SIF. According to the difference, model of evaluating the stability of protein to SGF/SIF was established.
Intestinal Mucosa of Celiacs in Remission Is Unable To Abolish Toxicity of Gliadin Peptides on in Vitro Developing Fetal Rat Intestine And Cultured Atrophic Celiac Mucosa

ABSTRACT: Subfraction 2R of fraction 9 from a peptic-tryptic-pancreatic digest of wheat gliadin is known to be toxic in vivo to celiac patients. We have found that fractions 9 and 2R inhibit the in vitro development of fetal rat intestine and the increase of enterocyte height occurring in organ culture of atrophic celiac mucosa (0.1–0.5 mg/ml medium). Other peptide fractions of the gliadin digest are devoid of such in vitro effects. Subfraction 2R, after incubation with morphologically normal small intestinal mucosa of celiacs in remission and ultrafiltration, was still very active in both culture systems at low concentration (0.1 mg/ml); on the contrary, subfraction 2R was inactivated after incubation with normal mucosa. These results are compatible with the hypothesis that there is a mucosal defect in handling gliadin peptides in celiac disease, and suggest that there is either a primary (or secondary) enzyme deficiency or some other mechanism operating in the intestinal mucosa of celiac patients in remission.
Detecting Double Compressed JPEG Images by Using Moment Features of Mode Based DCT Histograms

The double compression of JPEG images is one of the important evidences of image tampering. The paper proposes a novel passive double compressed JPEG image detection algorithm using the moment features of the modes based DCT histogram's characteristic function. Support vector machine is used as the classifier. Experimental results demonstrate that the proposed algorithm significantly increases the detection accuracy when the first compressing quality factor is large such as 95. In order to further improve the overall detection accuracy of double compressed JPEG in various quality factors, the paper proposes an improved algorithm by combing the moment features with the Mode Based Fist Digit features (MBFDF). The experimental results show that the overall detection accuracies can be further improved and the proposed algorithm outperforms some traditional methods, especially when the first compressing quality factor is large such as 95.
Evaluation of phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) and epidermal growth factor receptor (EGFR) gene mutations in pancreaticobiliary adenocarcinoma.

BACKGROUND Phosphatidylinositol-3-kinase (PI3K) activation involves the epidermal growth factor receptor (EGFR) and plays an important role in cell survival signaling in pancreaticobiliary cancer. EGFR gene mutations have been correlated with clinical response to EGFR inhibitors in patients with advanced non-small cell lung cancer. This study examined the prevalence of PIK3CA and EGFR mutations in pancreaticobiliary cancer where erlotinib, an EGFR inhibitor, is approved for therapy. METHODS Thirty patients who underwent pancreatectomy for pancreaticobiliary carcinoma were identified. Genomic DNA was extracted from formalin fixed paraffin embedded tumor and adjacent normal tissue, and exons 9 and 20 (for the PIK3CA gene) and exons 18-21 (for the EGFR gene) were amplified by PCR and sequenced. Literature review on EGFR and/or PIK3CA mutations in pancreaticobiliary adenocarcinomas was conducted. RESULTS No mutations in either PIK3CA or EGFR genes were identified. The study identified one synonymous single nucleotide polymorphism (SNP) (rs1050171) in the coding region of EGFR. A previously unreported change, suspected to be a SNP, was observed in intron 18 of EGFR (IVS18+15, C>T). Review of the literature showed EGFR mutation rate of 2% and 10.5% in pancreatic and biliary tract carcinomas, respectively. PIK3CA mutations were found in 3.6% and 11.7% of pancreatic and biliary tract carcinomas, respectively. CONCLUSIONS A low prevalence of EGFR or PIK3CA mutations exists in pancreatic cancer (<5%), indicating that mutation screening may not be as useful in determining prognosis or response to targeted inhibition.
INBREEDING AND HAPLOID CHROMOSOMES: A RESPONSE TO HEDRICK (2011)

We have shown that inbreeding allows maternally transmitted organelles to respond to selection on male‐specific fitness effects (Wade and Brandvain 2009, see also Unckless and Herren 2009). Hedrick (2011) confirms our results, but takes issue with our characterization of “inbreeding” at mitochondrial loci. The reason for this disagreement is straightforward—we define inbreeding as the process of mating between relatives, whereas Hedrick (2011) defines inbreeding as increased homozygosity at autosomal loci genome‐wide, which occurs because of mating between relatives. Here, we insist that our definition is not incorrect, and highlight some benefits of our view.
Fourier rebinning of time-of-flight PET data

This paper explores fast reconstruction strategies for 3D time-of-flight (TOF) positron emission tomography (PET), based on 2D data rebinning. Starting from pre-corrected 3D TOF data, a rebinning algorithm estimates for each transaxial slice the 2D TOF sinogram that would have been acquired by a single-ring scanner. The rebinned sinograms can then be reconstructed using any algorithm for 2D TOF reconstruction. We introduce TOF-FORE, an approximate rebinning algorithm obtained by extending the Fourier rebinning method for non-TOF data. In addition, we identify two partial differential equations that must be satisfied by consistent 3D TOF data, and use them to derive exact rebinning algorithms and to characterize the degree of the approximation in TOF-FORE. Numerical simulations demonstrate that TOF-FORE is more accurate than two different TOF extensions of the single-slice rebinning method, and suggest that TOF-FORE will be a valuable tool for practical TOF PET in the range of axial apertures and time resolutions typical of current scanners.
IL-4-Induced Priming of Human Intestinal Mast Cells for Enhanced Survival and Th2 Cytokine Generation Is Reversible and Associated with Increased Activity of ERK1/2 and c-Fos1

In synergy with stem cell factor (SCF), IL-4 strongly enhances mast cell proliferation and shifts IgE-dependent cytokine production in mature human mast cells toward an increased release of Th2 cytokines such as IL-3, IL-5, and IL-13 and a decreased IL-6 expression. In this study we analyzed the kinetics and the mechanisms of these IL-4 effects on mast cells purified from intestinal tissue. If the cells were first cultured with IL-4 for 14 days and then without IL-4 for another 14 days, mast cells lost the capacity of producing higher amounts of Th2 cytokines and regained the capacity of producing IL-6. The IL-4-induced up-regulation of mast cell proliferation and FcεRI expression was also reversible if IL-4 was withdrawn for 14 days. Interestingly, in contrast to IL-4, proliferation and phenotype of human intestinal mast cells were not affected by IL-13 although both cytokines were capable of inducing STAT6 activation. Instead, IL-4 treatment (but not IL-13 treatment) was associated with an increased activity of ERK1/2 and c-Fos, the downstream target of ERK1/2 and component of the transcription factor AP-1. Consistently, mast cell proliferation and cytokine expression in response to IL-4 was blocked by the MEK inhibitor PD98059. In summary, our data show that the IL-4 effects on human intestinal mast cell functions are reversible and accompanied by an increased activity of ERK1/2 and c-Fos.
Associations between genetic obesity susceptibility and early postnatal fat and lean mass: an individual participant meta-analysis.

IMPORTANCE Patterns of body size and body composition associated with genetic obesity susceptibility inform the mechanisms that increase obesity risk. OBJECTIVE To test associations between genetic obesity susceptibility, represented by a combined obesity risk-allele score, and body size or body composition at birth to age 5 years. DESIGN, SETTING, AND PARTICIPANTS A total of 3031 children from 4 birth cohort studies in England, France, and Spain were included in a meta-analysis. EXPOSURES A combined obesity risk-allele score was calculated from genotypes at 16 variants identified by genome-wide association studies of adult body mass index (BMI). MAIN OUTCOMES AND MEASURES Outcomes were age- and sex-adjusted SD scores (SDS) for weight, length/height, BMI, fat mass, lean mass, and percentage of body fat at birth as well as at ages 1, 2 to 3, and 4 to 5 years. RESULTS The obesity risk-allele score was not associated with infant size at birth; at age 1 year it was positively associated with weight (β [SE], 0.020 [0.008] SDS per allele; P = .009) and length (β [SE], 0.020 [0.008] SDS per allele; P = .01), but not with BMI (β [SE], 0.013 [0.008] SDS per allele; P = .11). At age 2 to 3 years these associations were stronger (weight: β [SE], 0.033 [0.008] SDS per allele; P < .001; height: β [SE], 0.025 [0.008] SDS per allele; P < .001) and were also seen for BMI (β [SE], 0.024 [0.008] SDS per allele; P = .003). The obesity risk-allele score was positively associated with both postnatal fat mass (1 year: β [SE], 0.032 [0.017] SDS per allele; P = .05; 2-3 years: β [SE], 0.049 [0.018] SDS per allele; P = .006; and 4-5 years: β [SE], 0.028 [0.011] SDS per allele; P = .009) and postnatal lean mass (1 year: β [SE], 0.038 [0.014] SDS per allele; P = .008; 2-3 years: β [SE], 0.064 [0.017] SDS per allele; P < .001; and 4-5 years: β [SE], 0.047 [0.011] SDS per allele; P < .001), but not with the percentage of body fat (P > .15 at all ages). CONCLUSIONS AND RELEVANCE Genetic obesity susceptibility appears to promote a normally partitioned increase in early postnatal, but not prenatal, growth. These findings suggest that symmetrical rapid growth may identify infants with high life-long susceptibility for obesity.