Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemical analysis of keratinocyte growth factor and fibroblast growth factor 10 expression in psoriasis

Abstract: The pathogenic mechanism underlying the hyperproliferation of keratinocytes in psoriasis is still not completely clarified. The production of cytokines released by activated T lymphocytes infiltrating the upper dermis probably has a crucial role. Even dermal fibroblasts can participate in the process through the secretion of growth factors, and some studies have reported an increased expression of the insulin‐like growth factor 1. Few studies, however, have focused on the possible involvement of the keratinocyte growth factor (KGF/FGF‐7) and the fibroblast growth factor 10 (FGF‐10/KGF‐2), which are secreted by fibroblasts and stimulate keratinocyte proliferation acting through a receptor specifically expressed by epithelial cells. The aim of this study was to investigate the expression of KGF and FGF‐10 on the skin of patients with psoriasis by immunohistochemical analysis and to evaluate the correlation with the lymphocyte infiltrate and the epidermal proliferation. Immunostaining for KGF and FGF‐10 showed that both the growth factors are upregulated in the upper dermis of psoriatic skin, and that the expression is correlated with the presence of T‐cell infiltrate and with keratinocyte proliferation. Our data suggest that in psoriatic lesions activated lymphocytes can stimulate fibroblasts to produce KGF and FGF‐10, which in turn contribute to sustain the hyperproliferative status of the keratinocytes.
Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens1

Restriction of T cell responses to a few epitopes (immunodominance) is a central feature of immune responses. We analyzed the entire transcriptome of effector CD8 T cells specific for a dominant (H7a) and a cryptic (HY) mouse Ag and performed a longitudinal analysis of selected T cell differentiation markers. We found that Ag specificity had a relatively modest influence on the repertoire of genes that are transcriptionally modulated by the CD8 T cell differentiation program. Although the differentiation programs of anti-H7a and anti-HY T cells were similar, they did not progress simultaneously. The expansion peak of anti-H7a T cells was reached on day 10 while that of anti-HY T cells was attained on days 15–20. Between days 10 and 20, anti-H7a T cells were in the contraction phase and anti-HY T cells in the expansion phase. Furthermore, expansion and development of effector function were well-synchronized in anti-H7a T cells but were disconnected in anti-HY T cells. We propose that, by leading to selective expansion of the fittest CD8 T cells, immunodominance may be beneficial to the host. Inhibition of the T cell response to cryptic Ag would ensure that host resources (APC, cytokines) for which T cells compete are devoted to T cells with the best effector potential. One implication is that favoring expansion of the fittest effector T cells in general may be more important than increasing the diversity of the T cell repertoire.
The immune system as a chronotoxicity target of the anticancer mTOR inhibitor everolimus

ABSTRACT The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing. C57BL/6J mice were synchronized with light-dark 12h:12h, with L onset at Zeitgeber Time (ZT) 0. Everolimus was administered orally to male (5 mg/kg/day) and female mice (15 mg/kg/day) at ZT1, during early rest span or at ZT13, during early activity span for 4 weeks. Body weight loss, as well as hematological, immunological and biochemical toxicities, were determined. Spleen and thymus were examined histologically. Everolimus toxicity was less severe following dosing at ZT13, as compared to ZT1, as shown with least body weight inhibition in both genders; least reductions in thymus weight both in males (p < 0.01) and females (p < 0.001), least reduction in female spleen weight (p < 0.05), and less severe thymic medullar atrophy both in males (p < 0.001) and females (p < 0.001). The mean circulating counts in total leukocytes, total lymphocytes, T-helper and B lymphocytes displayed minor and non-significant changes following dosing at ZT13, while they were decreased by 56.9% (p < 0.01), 45.5% (p < 0.01), 43.1% (p < 0.05) and 48.7% (p < 0.01) after everolimus at ZT1, respectively, in only male mice. Chronotherapy of everolimus is an effective way to increase the general tolerability and decrease toxicity on the immune system.
A Jacob/Nsmf Gene Knockout Results in Hippocampal Dysplasia and Impaired BDNF Signaling in Dendritogenesis

Jacob, the protein encoded by the Nsmf gene, is involved in synapto-nuclear signaling and docks an N-Methyl-D-Aspartate receptor (NMDAR)-derived signalosome to nuclear target sites like the transcription factor cAMP-response-element-binding protein (CREB). Several reports indicate that mutations in NSMF are related to Kallmann syndrome (KS), a neurodevelopmental disorder characterized by idiopathic hypogonadotropic hypogonadism (IHH) associated with anosmia or hyposmia. It has also been reported that a protein knockdown results in migration deficits of Gonadotropin-releasing hormone (GnRH) positive neurons from the olfactory bulb to the hypothalamus during early neuronal development. Here we show that mice that are constitutively deficient for the Nsmf gene do not present phenotypic characteristics related to KS. Instead, these mice exhibit hippocampal dysplasia with a reduced number of synapses and simplification of dendrites, reduced hippocampal long-term potentiation (LTP) at CA1 synapses and deficits in hippocampus-dependent learning. Brain-derived neurotrophic factor (BDNF) activation of CREB-activated gene expression plays a documented role in hippocampal CA1 synapse and dendrite formation. We found that BDNF induces the nuclear translocation of Jacob in an NMDAR-dependent manner in early development, which results in increased phosphorylation of CREB and enhanced CREB-dependent Bdnf gene transcription. Nsmf knockout (ko) mice show reduced hippocampal Bdnf mRNA and protein levels as well as reduced pCREB levels during dendritogenesis. Moreover, BDNF application can rescue the morphological deficits in hippocampal pyramidal neurons devoid of Jacob. Taken together, the data suggest that the absence of Jacob in early development interrupts a positive feedback loop between BDNF signaling, subsequent nuclear import of Jacob, activation of CREB and enhanced Bdnf gene transcription, ultimately leading to hippocampal dysplasia.
Calcium Score: Semiautomatic Calculation Using Different Vendors Versus Fully Automatic Software

Objectives Recent advances in technology have resulted in a multitude of cardiac imaging postprocessing software products from vendors unrelated to the scanner on which the cardiac study was initially performed. A fully automatic calcium score software has also become available. We assess the intervendor variability of calcium score measurement using the semiautomatic software provided by the scanner vendor versus an unrelated vendor versus fully automatic software. Methods All consecutive patients who had a calcium score performed from March 2007 to January 2008 were included in this study. The studies were performed on two 64-slice computed tomographic scanners from 2 different vendors. The allocation of the patient to the specific scanner was done according to scanner and technologist availability. The studies were read twice by a cardiac radiologist and a general radiologist with at least 3 months’ interval at a workstation specified by the computed tomographic scanner vendor and then at an unrelated workstation, with semiautomatic software. Calcium score was also independently performed by the fully automatic software, blinded to the results of previous readings. Agreement was tested with Pearson correlation coefficient, Bland-Altman graphs, and the Fleiss &kgr; test. Results The study population included 101 patients: 70 patients scanned at 1 scanner and 31 at a different scanner. Intervendor variability for the 2 groups had &kgr; = 0.98 ± 0.01 and &kgr; = 0.96 ± 0.02; interobserver variability had &kgr; = 1. Semiautomatic versus automatic variability showed &kgr; = 0.88 to 0.94. Conclusions Because of very strong agreement between the calcium score measurements obtained by semiautomatic and fully automatic software by different vendors, calcium score measurements can be performed robustly at vendor-specific software, nonrelated software, or fully automatic software.
Intensive practice of a cognitive task is associated with enhanced functional integration in schizophrenia

Background There is increasing evidence that the frequently reported working memory impairments in schizophrenia might be partly due to an alteration in the functional connectivity between task-relevant areas. However, little is known about the functional connectivity patterns in schizophrenia patients during learning processes. In a previous study, Koch et al. [Neuroscience (2007) 146, 1474–1483] have demonstrated stronger exponential activation decreases in schizophrenia patients during overlearning of short-term memory material. The question arises whether these differential temporal patterns of activation in schizophrenia patients and controls are going along with changes in task-related functional connectivity. Method Therefore, in the current study, 13 patients with schizophrenia and 13 controls were studied while performing a short-term memory task associated with increasing overlearning of verbal stimulus material. Functional connectivity was investigated by analyses of psychophysiological interactions (PPI). Results Results revealed significant task-related modulation of functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and a network including the right DLPFC, left ventrolateral prefrontal cortex, premotor cortex, right inferior parietal cortex, left and right cerebellum as well as the left occipital lobe in patients during the course of overlearning and practice. No significant PPI results were detectable in controls. Conclusions Activation changes with practice were associated with high functional connectivity between task-relevant areas in schizophrenia patients. This could be interpreted as a compensatory resource allocation and network integration in the context of cortical inefficiency and may be a specific neurophysiological signature underlying the pathophysiology of schizophrenia.
Heavy Metal Coprecipitation with Hydrozincite [Zn5(CO3)2(OH)6] from Mine Waters Caused by Photosynthetic Microorganisms

ABSTRACT An iron-poor stream of nearly neutral pH polluted by mine tailings has been investigated for a natural phenomenon responsible for the polishing of heavy metals in mine wastewaters. A white mineralized mat, which was determined to be hydrozincite [Zn5(CO3)2(OH)6] by X-ray diffraction analysis, was observed in the stream sediments mainly in spring. The precipitate shows a total organic matter residue of 10% dry weight and contains high concentrations of Pb, Cd, Ni, Cu, and other metals. Scanning electron microscopy analysis suggests that hydrozincite is mainly of biological origin. Dormant photosynthetic microorganisms have been retrieved from 1-year-old dry hydrozincite. The autofluorescent microorganisms were imaged by a scanning confocal laser microscope. A photosynthetic filamentous bacterium, classified asScytonema sp. strain ING-1, was found associated with microalga Chlorella sp. strain SA1. This microbial community is responsible for the natural polishing of heavy metals in the water stream by coprecipitation with hydrozincite.
The role of pedometers in the assessment of intermittent claudication.

OBJECTIVES to evaluate the role of pedometers in the assessment of patients with intermittent claudication by comparing them with treadmill testing, post-exercise ankle brachial pressure index (ABPI) and physical function questionnaires. PATIENTS AND METHODS fifty patients with intermittent claudication were prospectively assessed by treadmill examination measuring maximum walking distance (MWD) and post-exercise ABPI. Three physical function questionnaires: (1) Medical Outcome Study Short Form-36 (MOS SF-36), Physical Function (PF). (2) MOS SF-36 Role limitation due to Physical Problems (RP). (3) Walking Impairment Questionnaire (WIQ) were completed. Pedometers were used for one week and the daily average number of steps taken by each patient recorded. Pedometers scores were compared with MWD, post-exercise ABPI and physical function questionnaires scores using Spearman correlation test. RESULTS pedometers estimation of daily physical activity moderately correlated with MWD (Rho=0.35, p=0.01), post-exercise ABPI (Rho=0.35, p=0.01), MOS-SF 36 PF (Rho=0.31, p=0.02), MOS-SF RP (Rho=0.28, p=0.05) and with WIQ (Rho=0.42, p=0.003). CONCLUSIONS they moderately correlate with treadmill testing, post-exercise ABPI, and with physical function questionnaires. Pedometers may provide a simple and cheap alternative for the assessment of physical and functional disability in intermittent claudication.
Biomarkers of exposure, effect, and susceptibility in workers exposed to chloronitrobenzenes

Abstract Biomonitoring methods were applied to workers exposed to high levels of chloronitrobenzenes. The external dose, internal dose, biologically effective dose, and biological effects were determined. Individual susceptibility was assessed by analyzing genetic polymorphisms of glutathione S-transferases M1, P1 and T1, and N-acetyltransferases 1 and 2. When the markers of exposure and susceptibility were compared with the frequency of chromosomal aberrations, clinical blood and urine parameters, and health effects typical of chloronitrobenzenes exposure, only a few of the comparisons were statistically significant. A statistically significantly higher frequency of chromosomal aberrations was detected in workers with a high level of hemoglobin-adducts.
Multiple Interactions of Auxilin 1 with Clathrin and the AP-2 Adaptor Complex*

The removal of the clathrin coat is essential for vesicle fusion with acceptor membranes. Disassembly of the coat involves hsc70, which is specifically recruited by members of the auxilin protein family to clathrin lattices. In vitro,this function of auxilin does not require the globular amino-terminal domain of the clathrin heavy chain, which is known to play a prominent role in the interaction of clathrin with adaptors and numerous endocytic accessory proteins. Here we report the unexpected finding that the neuron-specific form of auxilin (auxilin 1) can also associate with the clathrin amino-terminal domain. This interaction is mediated through tandemly arranged sites within the auxilin 1 carboxyl-terminal segment 547–910. The overlapping auxilin 1 fragments 547–714 and 619–738 bind the clathrin terminal domain with high affinity, whereas auxilin 1-(715–901) interacts only poorly with it. All three fragments also associate with the clathrin distal domain and the α-appendage domain of AP-2. Moreover, they support efficient assembly of clathrin triskelia into regular cages. A novel uncoating assay was developed to demonstrate that auxilin 1-(715–901) functions efficiently as a cofactor for hsc70 in the uncoating of clathrin-coated vesicles. The multiple protein-protein interactions of auxilin 1 suggest that its function in endocytic trafficking may be more complex than previously anticipated.
Mobile contingency locus controlling Escherichia coli K1 polysialic acid capsule acetylation

Escherichia coli K1 is part of a reservoir of adherent, invasive facultative pathogens responsible for a wide range of human and animal disease including sepsis, meningitis, urinary tract infection and inflammatory bowel syndrome. A prominent virulence factor in these diseases is the polysialic acid capsular polysaccharide (K1 antigen), which is encoded by the kps/neu accretion domain inserted near pheV at 67 map units. Some E. coli K1 strains undergo form (phase) variation involving loss or gain of O‐acetyl esters at carbon positions 7 or 9 of the individual sialic acid residues of the polysialic acid chains. Acetylation is catalysed by the receptor‐modifying acetyl coenzyme‐A‐dependent O‐acetyltransferase encoded by neuO, a phase variable locus mapping near the integrase gene of the K1‐specific prophage, CUS‐3, which is inserted in argW at 53.1 map units. As the first E. coli contingency locus shown to operate by a translational switch, further investigation of neuO should provide a better understanding of the invasive K1 pathotype. Minimal estimates of morbidity and economic costs associated with human infections caused by extraintestinal pathogenic E. coli strains such as K1 indicate at least 6.5 million cases with attendant medical costs exceeding $2.5 billion annually in the United States alone.
Endotoxin Inhibits Intestinal Epithelial Restitution through Activation of Rho-GTPase and Increased Focal Adhesions*

Diseases of gut inflammation such as neonatal necrotizing enterocolitis (NEC) result after an injury to the mucosal lining of the intestine, leading to translocation of bacteria and endotoxin (lipopolysaccharide). Intestinal mucosal defects are repaired by the process of intestinal restitution, during which enterocytes migrate from healthy areas to sites of injury. In an animal model of NEC, we determined that intestinal restitution was significantly impaired compared with control animals. We therefore sought to determine the mechanisms governing enterocyte migration under basal conditions and after an endotoxin challenge. Here we show that the cytoskeletal reorganization and stress fiber formation required for migration in IEC-6 enterocytes requires RhoA. Enterocytes were found to express the endotoxin receptor Toll-like receptor 4, which served to bind and internalize lipopolysaccharide. Strikingly, endotoxin treatment significantly inhibited intestinal restitution, as measured by impaired IEC-6 cell migration across a scraped wound. Lipopolysaccharide was found to increase RhoA activity in a phosphatidylinositol 3-kinase-dependent manner, leading to an increase in phosphorylation of focal adhesion kinase and an enhanced number of focal adhesions. Importantly, endotoxin caused a progressive, RhoA-dependent increase in cell matrix tension/contractility, which correlated with the observed impairment in enterocyte migration. We therefore conclude that endotoxin inhibits enterocyte migration through a RhoA-dependent increase in focal adhesions and enhanced cell adhesiveness, which may participate in the impaired restitution observed in experimental NEC.
Effects of COX inhibition and LPS on formalin induced pain in the infant rat

In the adult, immune and neural processes jointly modulate pain. During development, both are in transition and little is known about the role that the immune system plays in pain processing in infants and children. The objective of this study was to determine if inhibition or augmentation of the immune system would alter pain processing in the infant rat, as it does in the adult. In Experiment 1, rat pups aged 3, 10, or 21 (PN3, PN10, and PN21) days of age were pretreated with NS398 (selective cyclooxygenase (COX)‐2 inhibitor) or SC560 (selective COX‐1 inhibitor) and tested in the intraplantar formalin test to assess effects of COX inhibition on nociception. Neither drug had an effect on the behavioral response at PN3 or PN10 pups but both drugs attenuated nociceptive scores in PN21 pups. cFos expression in the spinal cord likewise was reduced only at PN21. In Experiment 2, pups were injected with lipopolysaccharide (LPS) prior to the formalin test at PN3 or PN21. LPS increased the nociceptive response more robustly at PN21 than at PN3, while increasing cytokine mRNA equally at both ages. The augmentation of pain responding at PN21 was largely during the late stages of the formalin test, as reported in the adult. These data support previous findings demonstrating late maturing immune modulation of nociceptive behaviors. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 1068–1079, 2015
Hypoglycemia associated with the use of fluoxetine.

HYPOGLYCEMIA HAS many causes in patients who do not have diabetes mellitus, in contrast to patients with diabetes mellitus, in whom hypoglycemia is most often due to the use of insulin or oral hypoglycemic agents. We report a case of symptomatic hypoglycemia associated with fluoxetine use in a patient with non-insulin-dependent diabetes mellitus. Symptoms of sweating, tremor, or anxiety occur in 10% or more of patients taking fluoxetinel2 and can eas-ily be confused with hypoglycemia that occurs in diabetic patients.3 In the case reported here, symptomatic hypoglycemia was associated with increased blood insulin levels during a 72-hour fast while the patient was taking fluoxetine. This case emphasizes the importance in evaluating the occurrence of hypoglycemia of discontinuing all nonessential medications during a 72-hour fast.
Validation of a Swedish version of the Facial Disability Index (FDI) and the Facial Clinimetric Evaluation (FaCE) scale

Abstract Conclusion: Swedish versions of the Facial Disability Index (FDI) and Facial Clinimetric Evaluation (FaCE) scale are psychometrically valid. Both questionnaires can be used for clinical studies on peripheral facial palsy patients, and provide important information on quality of life. Objectives: To translate and validate Swedish versions of the FDI and FaCE scale in patients with peripheral facial palsy. Methods: Translation of the original questionnaires followed international guidelines. Internal consistency and test–retest stability were assessed in adult patients with stable peripheral facial palsy. Facial function was examined with the Sunnybrook and House-Brackmann scales. Subjects answered the questionnaires twice with a 2-week interval. Validity was assessed by comparing FDI and FaCE scale scores to SF-36 and Sunnybrook/House-Brackmann scores. Results: Ninety-three patients were included, 53% women and 47% men, mean age 56.9 years and mean duration of palsy 51.9 months. The questionnaires showed good/excellent psychometric properties with Cronbach's α scores between 0.76 and 0.92. In the test–retest analysis, intra-class correlation coefficients were very good for both questionnaires with scores of 0.83–0.97. Both questionnaires showed good sensitivity to discriminate between patients with varying degrees of facial dysfunction. Moderate to strong correlation was found between the social domains in the questionnaires when compared with the equivalent domains in SF-36.
The crystal structure of thermally- and stress-induced Martensites in Ni2MnGa single crystals

Deformation behavior of Ni2MnGa single crystals uniaxially loaded in compression and tension along the 〈100〉β1 and 〈110〉β1 axes were investigated. It was shown that three successive stress-induced structural transitions may be observed for specimens tensed along the 〈100〉β1 or compressed along the 〈110〉β1 direction, while only one transition was stress-induced in compression along the 〈100〉β1 axis. The crystal structure of stress-induced and thermal martensite was identified and related reversible deformation values for different loading geometry were estimated.