Miracle-dz/UniFAR-FTUs huggingface dataset:
Low Mass Blood Peptides Discriminative of Inflammatory Bowel Disease (IBD) Severity: A Quantitative Proteomic Perspective*

Breakdown of the protective gut barrier releases effector molecules and degradation products into the blood stream making serum and plasma ideal as a diagnostic medium. The enriched low mass proteome is unexplored as a source of differentiators for diagnosing and monitoring inflammatory bowel disease (IBD) activity, that is less invasive than colonoscopy. Differences in the enriched low mass plasma proteome (<25 kDa) were assessed by label-free quantitative mass-spectrometry. A panel of marker candidates were progressed to validation phase and “Tier-2” FDA-level validated quantitative assay. Proteins important in maintaining gut barrier function and homeostasis at the epithelial interface have been quantitated by multiple reaction monitoring in plasma and serum including both inflammatory; rheumatoid arthritis controls, and non-inflammatory healthy controls; ulcerative colitis (UC), and Crohn's disease (CD) patients. Detection by immunoblot confirmed presence at the protein level in plasma. Correlation analysis and receiver operator characteristics were used to report the sensitivity and specificity. Peptides differentiating controls from IBD originate from secreted phosphoprotein 24 (SPP24, p = 0.000086, 0.009); whereas those in remission and healthy can be differentiated in UC by SPP24 (p = 0.00023, 0.001), α-1-microglobulin (AMBP, p = 0.006) and CD by SPP24 (p = 0.019, 0.05). UC and CD can be differentiated by Guanylin (GUC2A, p = 0.001), and Secretogranin-1 (CHGB p = 0.035). Active and quiescent disease can also be differentiated in UC and CD by CHGB (p ≤ 0.023) SPP24 (p ≤ 0.023) and AMBP (UC p = 0.046). Five peptides discriminating IBD activity and severity had very little-to-no correlation to erythrocyte sedimentation rate, C-reactive protein, white cell or platelet counts. Three of these peptides were found to be binding partners to SPP24 protein alongside other known matrix proteins. These proteins have the potential to improve diagnosis and evaluate IBD activity, reducing the need for more invasive techniques. Data are available via ProteomeXchange with identifier PXD002821.
Differential Invasion of Trypanosoma brucei brucei and Lymphocytes into the Brain of C57BL/6 and 129Sv/Ev Mice

Trypanosoma brucei subspecies invade the brain parenchyma at late stages of human and experimental rodent infections. In this study, we compared the outcome of infection with T. b. brucei in MHC‐matched (H‐2b) C57BL/6 (B6) and 129Sv/Ev (Sv‐129). Sv‐129 showed higher parasitaemia and lower specific IgM (but not IgG) antibody levels than B6 mice. The number of trypanosomes, CD4+ and CD8+ T cells in the brain parenchyma was higher in B6 mice. B6 mice lost weight and showed higher cumulative mortality when compared with Sv‐129 mice. Higher levels of IL‐1β, IL‐6, IL‐10, TNF‐α, IFN‐γ, ICAM‐1 and E‐selectin, but low levels of TGF‐β mRNA were present in brains of B6 when compared with Sv‐129‐infected mice. Thus, host genetics differentially determine the invasion of T. b. brucei into the brain parenchyma, which is paralleled by the severity of inflammation in the brain and course of the disease, but not by parasitaemia nor by antibody titres.
Identification of a genetic element (psr) which negatively controls expression of Enterococcus hirae penicillin-binding protein 5

Enterococcus hirae ATCC 9790 produces a penicillin-binding protein (PBP5) of low penicillin affinity which under certain conditions can take over the functions of all the other PBPs. The 7.1-kb EcoRI fragment containing the pbp5 gene of this strain and of two mutants, of which one (E. hirae R40) overproduces PBP5 and the other (E. hirae Rev14) does not produce PBP5, was cloned in pUC18 and sequenced. In the 7.1-kb EcoRI fragment cloned from strain ATCC 9790, an open reading frame (psr) potentially encoding a 19-kDa protein was identified 1 kb upstream of the pbp5 gene. An 87-bp deletion in this element was found in the 7.1-kb EcoRI fragment cloned from strains R40 and Rev14. In addition, several base substitutions were found in the pbp5 genes of strains R40 and Rev14. One of these converted the 42nd codon, TCA, to the stop codon, TAA, in the pbp5 gene of Rev14. Escherichia coli strains were transformed with plasmids carrying the 7.1-kb EcoRI insert or a 2.6-kb HincII insert containing only the pbp5 gene of the three strains. Immunoblotting analysis of proteins expressed by these transformants showed that the 87-bp deletion in psr was associated with the PBP5 overproducer phenotype of strain R40 and the conversion of the TCA codon to the stop codon was associated with the PBP5 nonproducer phenotype of strain Rev14. None of the other nucleotide substitutions had any apparent effect on the level of PBP5 synthesized.
Characterization of a novel fibronectin‐binding surface protein in group A streptococci

Streptococcus pyogenes interacts with host fibronectin via distinct surface components. One of these components is the Sfbl protein (streptococcal fibronectin‐binding protein, now specified as class I), an adhesin that represents a protein family with characteristic features. Here we present the complete structure of a novel fibronectin‐binding protein of S. pyogenes, designated SfbII, which is distinct from the previously described Sfbl proteins. The sfbII gene originated from a λ EMBL3 library of chromosomal DNA from group A streptococcal strain A75 and coded for a 113kDa protein exhibiting features of membrane‐anchored surface proteins of Gram‐positive cocci. The expression of biologically active fusion proteins allowed the determination of the location of the fibronectin‐binding domain within the C‐terminal part of the protein. It consisted of two and a half repeats which share common motifs with fibronectin‐binding repeats of other streptococcal and staphylococcal proteins. Purified recombinant fusion protein containing this domain competitively inhibited the binding of fibronectin to the parental S. pyogenes strain. Furthermore, polyclonal antibodies against the binding domain specifically blocked the Sfbll receptor site on the streptococcal surface. No cross‐reactivity could be detected between anti‐Sfbll antibodies and the sfbl gene product, and vice versa, indicating that the two proteins do not share common immunogenic epitopes. Southern hybridization experiments performed with specific sfbll gene probes revealed the presence of the sfbll gene in more than 55% of 93 streptococcal isolates tested. The majority of the strains also harboured the sfbl gene, and 86% carried at least one of the two sfb genes.
An early fossil remora (Echeneoidea) reveals the evolutionary assembly of the adhesion disc

The adhesion disc of living remoras (Echeneoidea: Echeneidae) represents one of the most remarkable structural innovations within fishes. Although homology between the spinous dorsal fin of generalized acanthomorph fishes and the remora adhesion disc is widely accepted, the sequence of evolutionary—rather than developmental—transformations leading from one to the other has remained unclear. Here, we show that the early remora †Opisthomyzon (Echeneoidea: †Opisthomyzonidae), from the early Oligocene (Rupelian) of Switzerland, is a stem-group echeneid and provides unique insights into the evolutionary assembly of the unusual body plan characteristic of all living remoras. The adhesion disc of †Opisthomyzon retains ancestral features found in the spiny dorsal fins of remora outgroups, and corroborates developmental interpretations of the homology of individual skeletal components of the disc. †Opisthomyzon indicates that the adhesion disc originated in a postcranial position, and that other specializations (including the origin of pectination, subdivision of median fin spines into paired lamellae, increase in segment count and migration to a supracranial position) took place later in the evolutionary history of remoras. This phylogenetic sequence of transformation finds some parallels in the order of ontogenetic changes to the disc documented for living remoras.
Vibration-Induced Nystagmus After Acute Peripheral Vestibular Loss: Comparative Study With Other Vestibule-Ocular Reflex Tests in the Yaw Plane

Objective: To validate the role of vibration-induced nystagmus (VIN) detecting vestibular asymmetry by comparing several vestibulo-ocular reflex (VOR) parameters in the yaw plane. Study Design: Prospective validation study for diagnostic test. Setting: Tertiary referral center. Patients: Seventy-four patients with unilateral vestibular loss of acute onset without a history of fluctuating vestibular function and 24 healthy volunteers. Intervention: Spontaneous nystagmus, head-shaking nystagmus (HSN), and VIN using a 100 Hz handheld vibrator were recorded using a videonystagmography system. Canal paresis on the caloric test and the time constant (TC) on the step velocity test were examined as parameters of the laboratory test. Main Outcome Measures: Correlation analysis between horizontal VOR parameters was performed. Receiver operating characteristic (ROC) curves of these parameters were plotted, and the area under the ROC curve (AUC) was compared according to the lower limiting value of TC on step velocity test as well as the presence of unilateral vestibular loss. Results: VIN was observed in 64 (86%) of 74 patients, and it was directed toward the contralesional side in 98%. VIN showed a significant positive correlation with the canal paresis (r = 0.416, p < 0.001) and a negative correlation with the TC (r = −0.351, p < 0.005). ROC curves of several VOR parameters were compared according to the presence of unilateral vestibular loss. The AUC of VIN was 0.882, and the cutoff intensity of VIN was 2.5 degrees per second. The AUCs of the HSN and spontaneous nystagmus were 0.774 and 0.661, respectively. Conclusion: The lateralization value of VIN was comparable with caloric test and superior to HSN. VIN is a useful vestibular test detecting vestibular asymmetry in the evaluation of dizziness.
Certified athletic trainers in secondary schools: report of the council on scientific affairs, american medical association.

BACKGROUND In June 1997, the American Academy of Pediatrics introduced a resolution asking the American Medical Association (AMA) to support efforts to place certified athletic trainers in all secondary schools. The AMA Council on Scientific Affairs studied that resolution and presented this report to the AMA House of Delegates in June 1998. OBJECTIVE To identify the professional responsibilities, educational requirements, and current use of certified athletic trainers in the prevention and care of high school sports injuries. DATA SOURCES MEDLINE and HealthSTAR databases were searched for English-language articles published from 1980 to 1998. Additional references were derived from references in pertinent articles, communication with experts, and the Internet sites of athletic training and sports medicine associations. DATA SYNTHESIS One in 5 of approximately 6 million adolescents who participate in high school sports each year sustains a sport-related injury. Most of these injuries are minor and occur during practices rather than competitions. Approximately 1 of every 100000 high school athletes will sustain a catastrophic injury. About 35% of US high schools use the services of a certified athletic trainer, who, under a physician's supervision, is responsible for the prevention and care of athletic injuries and coordination of the school athletic health program. CONCLUSIONS/RECOMMENDATIONS Emphasis should be given to ensuring the health, safety, and well-being of participants in high school sports. Whereas most high school sports injuries are minor, adequately trained personnel should be present on site to ensure that such injuries are recognized early, treated immediately, and allowed to heal properly, thereby reducing the risk of more serious injury or reinjury. For such care, team physicians and coaches should have the assistance of a certified athletic trainer.
Downregulation of GbpB, a Component of the VicRK Regulon, Affects Biofilm Formation and Cell Surface Characteristics of Streptococcus mutans

ABSTRACT The virulence of the dental caries pathogen Streptococcus mutans relies in part on the sucrose-dependent synthesis of and interaction with glucan, a major component of the extracellular matrix of tooth biofilms. However, the mechanisms by which secreted and/or cell-associated glucan-binding proteins (Gbps) produced by S. mutans participate in biofilm growth remain to be elucidated. In this study, we further investigate GbpB, an essential immunodominant protein with similarity to murein hydrolases. A conditional knockdown mutant that expressed gbpB antisense RNA under the control of a tetracycline-inducible promoter was constructed in strain UA159 (UACA2) and used to investigate the effects of GbpB depletion on biofilm formation and cell surface-associated characteristics. Additionally, regulation of g bpB by the two-component system VicRK was investigated, and phenotypic analysis of a vicK mutant (UAvicK) was performed. GbpB was directly regulated by VicR, and several phenotypic changes were comparable between UACA2 and UAvicK, although differences between these strains existed. It was established that GbpB depletion impaired initial phases of sucrose-dependent biofilm formation, while exogenous native GbpB partially restored the biofilm phenotype. Several cellular traits were significantly affected by GbpB depletion, including altered cell shape, decreased autolysis, increased cell hydrophobicity, and sensitivity to antibiotics and osmotic and oxidative stresses. These data provide the first experimental evidence for GbpB participation in sucrose-dependent biofilm formation and in cell surface properties.
Severity‐dependent association between ganglion cell inner plexiform layer thickness and macular mean sensitivity in open‐angle glaucoma

To evaluate the structure–function relationship between macular mean sensitivity (mMS) and ganglion cell inner plexiform layer thickness (GCIPLT) according to glaucoma severity and to compare it with that between mMS and peripapillary retinal nerve fibre layer thickness (pRNFLT), using spectral‐domain (Cirrus) optical coherence tomography (OCT).
Two French Caucasian Families with Dominant Thalassemia-Like Phenotypes Due to Hyper Unstable Hemoglobin Variants: Hb Sainte Seve [Codon 118 (− T)] and Codon 127 [CAG→TAG (Gln→Stop])

We report two French Caucasian families suffering from dominant thalassemia-like phenotypes due to hyper unstable hemoglobin (Hb) variants. In both cases, molecular analysis revealed a defect localized in the third exon of the β-globin gene, resulting in dramatic changes of the Hb structure. The first one is a new variant, Hb Sainte Seve, that is associated with a frameshift mutation at codon 118 (− T). In the second family, the disease resulted from a truncated protein due to a stop mutation at codon 127 [CAG →TAG (Gln→Stop)]. These two observations are additional evidences of the important role played by helix H in Hb stability: its partial absence, or a large structural modification, seems to be the major reason for the hyper instability of such molecules.
The influence of deep (odontogenic) pain intensity, quality, and duration on the incidence and characteristics of referred orofacial pain.

This study examined the effects of the intensity, quality, and duration of odotogenic pain on the incidence, pattern, and clinical characteristics of pain referral in the orofacial region. Four hundred consecutive patients reporting with posterior toothache to the dental emergency clinic were included. Patients completed a standardized clinical questionnaire consisting of a numerical rating scale for pain intensity and chose verbal descriptors from a list of adjectives describing the quality of their pain. In addition, patients indicated sites to which pain referred by drawing on a mannequin* of the head and neck. Pain intensity was found to significantly affect the presence of referred pain (P < .005). However, neither duration nor quality of pain influenced the incidence of referred pain. Finally, pain referral occurred in vertical laminations as indicated on mannequin drawings, but these were not found to be diagnostic because of extensive horizontal overlap. The association of intensity and referral is attributed to central nervous system hyperexitability causing expansion of receptive fields and spread and referral of pain.
Enhancement of Antibody-Dependent Cellular Cytotoxicity of Neonatal Cells by Interleukin-2 (IL-2) and IL-12

ABSTRACT Newborn infants are more susceptible to infections due in part to deficiencies in the cytotoxic functions of their lymphocytes. We investigated the ability of interleukin-2 (IL-2) and IL-12 to enhance the cytotoxicity of neonatal (cord blood) and adult mononuclear cells (MNCs) in both natural killer (NK) cell and antibody-dependent cellular cytotoxicity (ADCC) assays. The cytotoxic activity of cord blood MNCs was less than 50% that of adult MNCs in most assays prior to exposure to cytokines. Incubation with IL-2 (100 U/ml) or IL-12 (1 ng/ml) for 18 h increased the NK cell activity (using K562 target cells) of both cord blood and adult MNCs, and the combination of IL-2 and IL-12 increased cord blood cytotoxicity threefold, making the cytotoxicity of cord blood cells equivalent to that of adult cells treated with the same cytokines. In ADCC assays with chicken erythrocyte targets, the combination of IL-2 and IL-12 increased the cytotoxicities of both cord blood and adult MNCs, with greater enhancement again seen with cord blood cells. In assays with NK cell-resistant CEM cells coated with human immunodeficiency virus (HIV) gp120 antigen in the presence of hyperimmune anti-HIV immunoglobulin, ADCC of cord blood MNCs was about 50% that of adult MNCs; ADCC of cord blood MNCs increased two- to threefold with the addition of IL-2 and IL-12, whereas ADCC of adult MNCs did not increase. Incubation of cord blood cells, but not adult cells, with IL-2 or IL-12 for 1 week increased the percentage of CD16+/CD56+ cells two- to fivefold and enhanced ADCC activity. Thus, IL-2 and IL-12 greatly enhance both the NK cell and ADCC activities of neonatal MNCs and increase the number of NK cells in longer-term culture.
Labor-Market Volatility in Matching Models with Endogenous Separations

The business-cycle behavior of a matching model with endogenous separations is studied in this paper. We show that whether aggregate productivity shocks have a larger effect on the vacancy-unemployment ratio than in a model with exogenous separations depends on whether worker productivity stochastically increases with tenure. The difference in the response is quantitatively small, however. We also show that the cleansing effect introduced by allowing for endogenous separations can help in reconciling the model with observed fluctuations in the unemployment rate, but not with those in the vacancy rate. Copyright The editors of the "Scandinavian Journal of Economics" 2008 .
Bradykinin Impairs and HOE 140 does not Protect Rat Hindlimb Skeletal Muscle Against Tourniquet-induced Reperfusion Injury

ABSTRACT Background: Bradykinin (BK) is used in different tissues. Dose-dependent studies have demonstrated that low doses protect against ischemia/reperfusion (I/R) injury while higher doses lead to adverse effects. Although the beneficial effects of BK infusion were observed in myocardium, its role on the I/R impact in skeletal muscle (SM) has not been fully clarified. Objective: This study was carried out to evaluate the effects of BK, administered in the hindlimbs of rats subjected to I/R. Methods: The study design included three experimental groups: Group 1 control (saline), Group 2 (bradykinin), and Group 3 (HOE 140, a BK2 receptor blocker). In all three groups, rats were subjected to hindlimb ischemia for a total of 2 h followed by continuous 4 h of reperfusion with pharmacological interventions. The methods include analysis of enzymes (lactate dehydrogenase—LDH and creatinine phosphokinase—CPK), cell membrane marker of injury (malondialdeyde—MDA), recruitment of neutrophils (myeloperoxidase—MPO), and apoptosis index (immunohistochemistry TUNEL in situ peroxidase dead end). Results: Except for the apoptotic index, all parameters studied were shown to be elevated in the reperfusion group intervened with BK. The blocking of BK2 receptors by HOE 140 did not affect the I/R injury. Conclusion: After 2 h of total ischemia, infusion of bradykinin during 4 h of reperfusion, worsened the I/R injury in the hindlimb skeletal muscle.
Fat and bone in children: Differential effects of obesity on bone size and mass according to fracture history

Fat mass predicts bone accrual in prepubertal children, but obese children have increased fracture risk. We hypothesised that bone size and mass would vary according to prior fracture in obese children. One hundred and three children (52 obese) underwent dual‐energy X‐ray absorptiometry (DXA) scanning of the lumbar spine, total body, and radial metaphysis and diaphysis. We derived body size–adjusted bone mineral density (BMD) estimates for each site using commonly employed procedures. Following adjustment for either age, age2 and weight, or height and weight based on a reference group of nonobese controls without previous fracture, obese children with prior fracture showed a 0.8 to 1.2 SD reduction in total body areal BMD (aBMD), a 3.0 SD decrease in lumbar (L2–4) aBMD, and a 2.0 SD reduction in radial shaft aBMD. These changes were significant at p < . 005. Lumbar volumetric BMD (vBMD) calculated by Carter and Kröger algorithms was significantly reduced in obese children with prior fracture (2.0 to 3.3 SD). Eighteen percent of obese children fulfilled the criteria for osteoporosis. Despite greater lean mass for height in obese children (p < .0001), total body bone mineral content (BMC) for lean mass was reduced (p = .002). Multiple regression models adjusting for height, weight, and gender demonstrated an inverse relationship between total body fat mass and total body, lumbar, and ultradistal radius BMC and aBMD. The data suggest that fat mass substantially inhibits bone accrual in children with prior fracture. These children may require targeted interventions to increase bone mass during adolescence to achieve optimal peak bone mass and reduce the risk of osteoporosis later in life. © 2010 American Society for Bone and Mineral Research