Miracle-dz/UniFAR-FTUs huggingface dataset:
PFP1, a Gene Encoding an Epc-N Domain-Containing Protein, Is Essential for Pathogenicity of the Barley Pathogen Rhynchosporium commune

ABSTRACT Scald caused by Rhynchosporium commune is an important foliar disease of barley. Insertion mutagenesis of R. commune generated a nonpathogenic fungal mutant which carries the inserted plasmid in the upstream region of a gene named PFP1. The characteristic feature of the gene product is an Epc-N domain. This motif is also found in homologous proteins shown to be components of histone acetyltransferase (HAT) complexes of fungi and animals. Therefore, PFP1 is suggested to be the subunit of a HAT complex in R. commune with an essential role in the epigenetic control of fungal pathogenicity. Targeted PFP1 disruption also yielded nonpathogenic mutants which showed wild-type-like growth ex planta, except for the occurrence of hyphal swellings. Complementation of the deletion mutants with the wild-type gene reestablished pathogenicity and suppressed the hyphal swellings. However, despite wild-type-level PFP1 expression, the complementation mutants did not reach wild-type-level virulence. This indicates that the function of the protein complex and, thus, fungal virulence are influenced by a position-affected long-range control of PFP1 expression.
Diagnostic Performance of Triggering Receptor Expressed on Myeloid Cells-1 and CD64 Index as Markers of Sepsis in Preterm Newborns

Objective: CD64 index and triggering receptor expressed on myeloid cells-1 are biomarkers on neutrophil polymorphonuclear cells with crucial role in sepsis. The study aim is to assess diagnostic performance, individually and combined, of CD64 index and triggering receptor expressed on myeloid cells-1 (surface marker/soluble form), in late-onset sepsis of preterm infants. Design: Observational study. Setting: Neonatal ICU. Patients: Sixteen septic and 16 control preterm infants, gestational age younger than 32 weeks and/or birth weigh less than 1500 g. Measurement and Main Results: Seventy preterm infants, free of sepsis were enrolled into the study. CD64 index and triggering receptor expressed on myeloid cells-1 were measured once between day 5 and 15 of life (T0) and once between day 16 and 25 (T1). At T1, 16 infants were assigned to septic group because of reported signs of sepsis and positive blood culture. From the remaining 54 infants, 16 of them who always remained free of sepsis had a blood sample at T1 and constituted the control group (n = 16). Comparing T1 vs T0, triggering receptor expressed on myeloid cells-1 polymorphonuclear cells percentage was significantly lower (p = 0.002) in septic group but not in control group; soluble triggering receptor expressed on myeloid cells-1 concentration did not show significant differences in both groups; CD64 index significantly increased (p = 0.0004) in septic group, while no difference was found in control group. Comparing septic with control group at T0, no differences were found in any markers. At T1, triggering receptor expressed on myeloid cells-1 polymorphonuclear cells percentage was significantly lower (p = 0.003) and CD64 index was higher (p = 0.00019) in septic infants. Triggering receptor expressed on myeloid cells-1 polymorphonuclear cells receiver operating characteristic curve indicated cutoff 62.12%, sensitivity 56.2%, specificity 93.5%, and area under the curve 0.8. CD64 index receiver operating characteristic curve indicated cutoff 2.85, sensitivity 87.5%, specificity 100%, and area under the curve 0.95. Combination of the two indexes was not useful in increasing individual diagnostic power. Conclusions: Despite limited sample size, CD64 index demonstrated to be a promising biomarker, with high specificity, to diagnose late-onset sepsis. Further investigations are needed to substantiate these findings. Triggering receptor expressed on myeloid cells-1 showed less valuable diagnostic role.
Maxwell's equations based 3D model of light scattering in the retina

The goal of this work is to develop a computational model of the human retina and simulate light scattering through its structure aiming to shed light on data obtained by optical coherence tomography in human retinas. Currently, light propagation in scattering media is often described by Mie's solution to Maxwell's equations, which only describes the scattering patterns for homogeneous spheres, thus limiting its application for scatterers of more complex shapes. In this work, we propose a discontinuous Galerkin method combined with a low-storage Runge-Kutta method as an accurate and efficient way to numerically solve the time-dependent Maxwell's equations. In this work, we report on the validation of the proposed methodology by comparison with Mie's solution, a mandatory step before further elaborating the numerical scheme towards the propagation of electromagnetic waves through the human retina.
A Fully Automated Framework for Segmentation and Stenosis Quantification of Coronary Arteries in 3D CTA Imaging

In this paper, we present a novel framework to segment and quantify stenosed coronary arteries in 3D contrast enhanced computed tomography angiography (CTA). According to our knowledge, no commercially available software package permits fully automated detection and assessment of atherosclerotic stenosis. Therefore, in clinical practice, the radiologist has to make a detailed evaluation, segment by segment, which is obviously a tedious and time consuming task. In the proposed framework, the main branches of the coronary arteries are firstly extracted from the volume datasets by using a localized region-based level sets framework. Next, calcified voxels are removed by a post processing step. The centreline of the coronaries is extracted by mesh contraction algorithm. Finally, we compute the circularity and the convex hull deficiency of the cross sections at specific locations along the coronary arteries, which are then used to automatically detect and identify the presence of calcified stenosis.
Additional Therapeutic Effect of Balneotherapy in Low Back Pain

Objectives: Balneotherapy has been widely used for treatment of chronic low back pain recently. However there are only a few clinical controlled trials on balneotherapy. The aim of the present study was to evaluate the effects of balneotherapy in patients with chronic low back pain. Methods: Sixty patients with lumbar spondylosis were included in the study. In Group 1, patients received both balneotherapy and physiotherapy and in Group 2, patients received only physiotherapy for three weeks. The intensity of the pain was evaluated by Visual Analog Scale (VAS) and functional disability was scored according to Revised Oswestry Index (ROI). Spinal mobility was assessed by the Schober and lateral flexion tests. Variables were evaluated before and after the three weeks of treatment. Results: The groups were comparable regarding age (P = 0.970) and sex (P = 0.357). There was no statistically significant difference between the two groups for baseline VAS (P = 0.838), Schober test (P = 0.226), and right (P = 0.642) and left (P = 0.674) lateral flexion measurements, and ROI scores (P = 0.798). At the end of the therapy, all clinical parameters significantly improved in patients in both of the groups (P < 0.05). VAS, Schober test, and ROI scores after the therapy were clearly superior in Group 1 in comparison to Group 2 (P < 0.05). Conclusion: The results of the present study reiterate that besides conventional physiotherapy, balneotherapy may be effective in the treatment of patients with chronic low back pain.
9-[2-(Phosphonomethoxy)propyl]adenine (PMPA) Therapy Prolongs Survival of Infant Macaques Inoculated with Simian Immunodeficiency Virus with Reduced Susceptibility to PMPA

ABSTRACT Simian immunodeficiency virus (SIV) infection of newborn rhesus macaques is a useful animal model of human immunodeficiency virus infection for the study of the emergence and clinical implications of drug-resistant viral mutants. We previously demonstrated that SIV-infected infant macaques receiving prolonged treatment with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) developed viral mutants with fivefold reduced susceptibility to PMPA in vitro and that the development of these mutants was associated with the development of a K65R mutation and additional compensatory mutations in reverse transcriptase (RT). To study directly the virulence and clinical implications of these SIV mutants, two uncloned SIVmac isolates with similar fivefold reduced in vitro susceptibilities to PMPA but distinct RT genotypes, SIVmac055 (K65R, N69T, R82K A158S, S211N) and SIVmac385 (K65R, N69S, I118V), were each inoculated intravenously into six newborn rhesus macaques; 3 weeks later, three animals of each group were started on PMPA treatment. All six untreated animals developed persistently high levels of viremia and fatal immunodeficiency within 4 months. In contrast, the six PMPA-treated animals, despite having persistently high virus levels, survived significantly longer: 5 to 9 months for the three SIVmac055-infected infants and ≥21 months for the three SIVmac385-infected infants. Virus from only one untreated animal demonstrated reversion to wild-type susceptibility and loss of the K65R mutation. In several other animals, additional RT mutations, including K64R and Y115F, were detected, but the biological role of these mutations is unclear since they did not affect the in vitro susceptibility of the virus to PMPA. In conclusion, this study demonstrates that although SIVmac mutants with the PMPA-selected K65R mutation in RT were highly virulent, PMPA treatment still offered strong therapeutic benefits. These results suggest that the potential emergence of HIV mutants with reduced susceptibility to PMPA in patients during prolonged PMPA therapy may not eliminate its therapeutic benefits.
High-Resolution Mass Spectrometry for Characterizing the Metabolism of Synthetic Cannabinoid THJ-018 and Its 5-Fluoro Analog THJ-2201 after Incubation in Human Hepatocytes.

BACKGROUND Despite increasing prevalence of novel psychoactive substances, no human metabolism data are currently available, complicating laboratory documentation of intake in urine samples and assessment of the drugs' pharmacodynamic, pharmacokinetic, and toxicological properties. In 2014, THJ-018 and THJ-2201, synthetic cannabinoid indazole analogs of JWH-018 and AM-2201, were identified, with the National Forensic Laboratory Information System containing 220 THJ-2201 reports. Because of numerous adverse events, the Drug Enforcement Administration listed THJ-2201 as Schedule I in January 2015. METHODS We used high-resolution mass spectrometry (HR-MS) (TripleTOF 5600(+)) to identify optimal metabolite markers after incubating 10 μmol/L THJ-018 and THJ-2201 in human hepatocytes for 3 h. Data were acquired via full scan and information-dependent acquisition triggered product ion scans with mass defect filter. In silico metabolite predictions were performed with MetaSite and compared with metabolites identified in human hepatocytes. RESULTS Thirteen THJ-018 metabolites were detected, with the major metabolic pathways being hydroxylation on the N-pentyl chain and further oxidation or glucuronidation. For THJ-2201, 27 metabolites were observed, predominantly oxidative defluorination plus subsequent carboxylation or glucuronidation, and glucuronidation of hydroxylated metabolites. Dihydrodiol formation on the naphthalene moiety was observed for both compounds. MetaSite prediction matched well with THJ-018 hepatocyte metabolites but underestimated THJ-2201 oxidative defluorination. CONCLUSIONS With HR-MS for data acquisition and processing, we characterized THJ-018 and THJ-2201 metabolism in human hepatocytes and suggest appropriate markers for laboratories to identify THJ-018 and THJ-2201 intake and link observed adverse events to these new synthetic cannabinoids.
A transcriptomic study reveals differentially expressed genes and pathways respond to simulated acid rain in Arabidopsis thaliana.

Acid rain, as a worldwide environmental issue, can cause serious damage to plants. In this study, we provided the first case study on the systematic responses of arabidopsis (Arabidopsis thaliana (L.) Heynh. ) to simulated acid rain (SiAR) by transcriptome approach. Transcriptomic analysis revealed that the expression of a set of genes related to primary metabolisms, including nitrogen, sulfur, amino acid, photosynthesis, and reactive oxygen species metabolism, were altered under SiAR. In addition, transport and signal transduction related pathways, especially calcium-related signaling pathways, were found to play important roles in the response of arabidopsis to SiAR stress. Further, we compared our data set with previously published data sets on arabidopsis transcriptome subjected to various stresses, including wound, salt, light, heavy metal, karrikin, temperature, osmosis, etc. The results showed that many genes were overlapped in several stresses, suggesting that plant response to SiAR is a complex process, which may require the participation of multiple defense-signaling pathways. The results of this study will help us gain further insights into the response mechanisms of plants to acid rain stress.
The new horizon in 2D electrophoresis: New technology to increase resolution and sensitivity

A principally new type of an electrophoresis setup for the second dimension of 2DE named HPE (high performance electrophoresis) has recently become available that provides excellent reproducibility much superior to traditional 2DE. It takes up ideas from early beginnings of 2DE which could not be satisfactory realized at that time. The new HPE system is in contrast to all other established systems a horizontal electrophoresis that employs a new type of precast polyacrylamide gels on film‐backing and runs on a multilevel flatbed electrophoresis apparatus. In a systematic approach we compared its features to traditional 2DE for the cytosolic proteome of Bacillus subtilis. Not only the reproducibility is enhanced, but also nearly all qualitative parameters as resolution, sensitivity, the number of protein spots (25% more), and the number of different proteins (also additional 25%) are markedly increased. More than 200 proteins were exclusively found in HPE. This new electrophoresis system does not use buffer tanks. No glass plates are needed. Therefore handling of gels is greatly facilitated and very simple to use even for personnel with low technical skills. The new HPE system is technically at the beginnings and further development with increased performance can be expected.
Deregulated expression of monocyte chemoattractant protein-1 (MCP-1) in arterial hypertension: role in endothelial inflammation and atheromasia

Objective Arterial hypertension is recurrently associated with inflammation of the endothelium as an effect of the upregulation of functional molecules, including cytokines, adhesion molecules and chemokines. However, the role of monocyte chemoattractant protein-1 (MCP-1) in maintaining the inflammatory state of endothelial cells (EC) that leads to the progressive cardiovascular damage is unclear. Design Here, we investigated the expression of MCP-1, its major cell source as well as recurrence of a defined polymorphism (−2518 MCP-1) apparently linked to endothelial damage in several diseases. Methods Serum MCP-1 was measured by enzyme-linked immunosorbent assay (ELISA) in 740 hypertensive patients, subdivided according to their individual organ damage. Expression of both MCP-1 and its receptor CCR2 was evaluated in circulating ECs and macrophages by flow cytometry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), while gene variants of MCP-1 were revealed by PCR. Results Soluble MCP-1 was significantly elevated in patients with diffuse atheromasia. Furthermore, it was overexpressed by ECs activated to attract macrophages via the MCP-1/CCR2 pathway, whereas the −2518 MCP-1 polymorphism was correlated with atherosclerosis in most patients. Conclusions. Overexpression of MCP-1 is predominant in hypertensive patients with atheromasia in the form of a defined polymorphism. Measurement of MCP-1 may thus reflect the degree of endothelial damage, while early detection of such a polymorphism may acquire a prognostic value in the development of atherosclerosis.
Triage of women with ASCUS and LSIL on Pap smear reports: management by repeat Pap smear, HPV DNA testing, or colposcopy?

BACKGROUND The purpose of this study was to determine the efficacy of a repeat Papanicolaou (Pap) smear and the Hybrid Capture tube-based (HCT) HPV DNA test for detecting cervical intraepithelial neoplasia (CIN) grade 2 or 3 in women with recent atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) Pap smear reports. METHODS Women with a recent Pap smear report of ASCUS (n = 169) or LSIL (n = 110) had a repeat Pap smear, sampling of the cervix for HCT HPV DNA assay and a colposcopy examination. Data were evaluated using three different triage thresholds for colposcopy examination: a repeat Pap smear of persistent ASCUS or more severe dysplasia, a finding of persistent LSIL or more severe dysplasia, and a carcinogenic HPV test result. RESULTS The sensitivity, specificity, and positive and negative predictive values for detecting CIN 2/3 were 70%, 45%, 7%, and 96% for a repeat Pap smear using an ASCUS-positive threshold and 20%, 86%, 8%, and 94% for a repeat Pap smear using an LSIL-positive threshold, respectively, when women with an initial ASCUS Pap smear were considered. HPV testing for carcinogenic viruses alone or in combination with a repeat Pap smear (using ASCUS as a positive threshold) yielded results of 50%, 67%, 9%, and 96%, respectively, and 70%, 37%, 7%, and 95%, respectively, for detecting CIN 2/3. In women with an initial LSIL Pap smear, respective values for detecting CIN 2/3 by a repeat Pap smear with an ASCUS threshold were 92%, 26%, 14%, and 96%, and for an LSIL threshold 23%, 64%, 8%, and 86%, respectively. Hybrid Capture HPV testing alone or in combination with a repeat Pap smear yielded 69%, 43%, 14%, and 91%, respectively, and 100%, 21%, 14%, and 100%, respectively. CONCLUSIONS A Pap smear triage threshold restricted to LSIL or more severe dysplasia for women with prior ASCUS or LSIL Pap smear results was clearly ineffective for detecting high-grade cervical precancerous lesions. In contrast, when the repeat Pap smear triage threshold was expanded to include persistent ASCUS as abnormal, 83% of the women with CIN 2/3 were detected. Detection of carcinogenic HPV DNA using the HCT test was almost as sensitive for detecting CIN 2/3 as a solitary repeat Pap smear using an ASCUS or more severe positive threshold. Combining the HPV test with a repeat Pap smear did not significantly improve the sensitivity of cytology for detecting high-grade CIN. This study suggests that women with ASCUS and particularly LSIL Pap smears should be referred for a colposcopy examination until better triage methods become available.
Development of Measures of Food Neophobia in Children

In order to construct a behavioral neophobia measure for children, we had 5-, 8- and 11-year-olds choose from ten novel and ten familiar foods which ones they were willing to taste. Meanwhile, their parents indicated their own willingness to taste each of the foods, predicted the children's willingness, estimated the number of times they and their children had eaten the foods, and completed trait measures of food neophobia for themselves and the children. The children's levels of behavioral neophobia were significantly related to both their levels of trait neophobia and their parents' predictions of their willingness to eat the foods (r = 0.38 and 0.34, respectively; p < 0.001). In addition, children's and parents' behavioral and trait neophobia scores were significantly related (both r = 0.31; p < 0.001). Finally, parents but not children were more neophobic with respect to foods of animal (vs. vegetable) origin.
C5a receptor enables participation of mast cells in immune complex arthritis independently of Fcγ receptor modulation.

OBJECTIVE Mast cells are tissue-resident immune sentinels that are implicated in the pathogenesis of inflammatory joint disease. The aim of this study was to test our hypothesis that complement fragments could be key activators of synovial mast cells in autoimmune arthritis. METHODS In vivo studies used the murine K/BxN arthritis model, a distal symmetric polyarthritis mediated by IgG immune complexes. Expression of C5aR on synovial mast cells was determined by immunohistochemical and functional studies. C5aR(-/-) and control mast cells were engrafted into mast cell-deficient WBB6 F1-Kit(w) /Kit(W-v) (W/Wv) mice to examine the requirement for this receptor in arthritis. C5aR-dependent activation of mast cells was investigated in C5aR(-/-) animals and in murine and human mast cell cultures. RESULTS Murine synovial mast cells express functional C5aR. Unlike their wild-type counterparts, C5aR(-/-) mast cells adoptively transferred into W/Wv mice were not competent to restore arthritis, despite equivalent synovial engraftment. Activation of C5aR(-/-) mast cells by K/BxN serum in vivo remained intact, indicating that C5aR is dispensable for normal IgG-mediated triggering. Consistent with this result, cultured mast cells treated with C5a failed to modulate the expression of Fcγ receptors (FcγR) or to otherwise alter the activation threshold. In human mast cells, C5a promoted the production of the neutrophil chemotaxin interleukin-8, and recruitment of neutrophils at 24 hours after serum administration was impaired in C5aR(-/-) mice, suggesting that enhanced neutrophil chemoattractant production underlies the requirement for C5aR on mast cells in arthritis. CONCLUSION Stimulation via C5aR is required to unleash the proinflammatory activity of synovial mast cells in immune complex arthritis, albeit via a mechanism that is distinct from C5a-modulated expression of FcγR.
Delayed Rectifier K+ Currents,IK, Are Encoded by Kv2 α-Subunits and Regulate Tonic Firing in Mammalian Sympathetic Neurons

Previous studies have revealed the presence of four kinetically distinct voltage-gated K+ currents,IAf,IAs,IK, andISS, in rat superior cervical ganglion (SCG) neurons and demonstrated thatIK and ISS are expressed in all cells, whereas IAf andIAs are differentially distributed. Previous studies have also revealed the presence of distinct components ofIAf encoded by α-subunits of the Kv1 and Kv4 subfamilies. In the experiments described here, pore mutants of Kv2.1 (Kv2.1W365C/Y380T) and Kv2.2 (Kv2.2W373C/Y388T) that function as Kv2 subfamily-specific dominant negatives (Kv2.1DN and Kv2.2DN) were generated to probe the functional role(s) of Kv2 α-subunits. Expression of Kv2.1DN or Kv2.2DN in human embryonic kidney-293 cells selectively attenuates Kv2.1- or Kv2.2-encoded K+currents, respectively. Using the Biolistics Gene Gun, cDNA constructs encoding either Kv2.1DN or Kv2.2DN [and enhanced green fluorescent protein (EGFP)] were introduced into SCG neurons. Whole-cell recordings from EGFP-positive Kv2.1DN or Kv2.2DN-expressing cells revealed selective decreases in IK. Coexpression of Kv2.1DN and Kv2.2DN eliminatesIK in most (75%) SCG cells and, in the remaining (25%) cells, IK density is reduced. Together with biochemical data revealing that Kv2.1 and Kv2.2 α-subunits do not associate in rat SCGs, these results suggest that Kv2.1 and Kv2.2 form distinct populations ofIK channels, and that Kv2 α-subunits underlie (most of) IK in SCG neurons. Similar to wild-type cells, phasic, adapting, and tonic firing patterns are evident in SCG cells expressing Kv2.1DN or Kv2.2DN, although action potential durations in tonic cells are prolonged. Expression of Kv2.2DN also results in membrane depolarization, suggesting that Kv2.1- and Kv2.2-encoded IK channels play distinct roles in regulating the excitability of SCG neurons.