Miracle-dz/UniFAR-FTUs huggingface dataset:
Two polymorphisms of CD44 3'UTR weaken the binding of miRNAs and associate with naso-pharyngeal carcinoma in a Chinese population.

OBJECTIVE CD44 is a member of adhesion molecule families whose function is closely associated with cancer cell metastatic spread and drug resistance. CD44 is expressed as a wide variety of isoforms but 3' untranslated region (3'UTR) is conserved relatively and it is confirmed that more than ten miRNAs regulate the expression of CD44. The aim of this paper is to investigate the association between polymorphisms existed in CD44 3'UTR and nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS We scanned 1.5kb of CD44 3'UTR in a 287 patients and 507 controls Chinese Han population. After statistical analysis we found that the minor alleles of rs13347 C/T and rs115214213 T/C are associated with NPC (OR = 1.94 95% CI = 1.44-2.62; OR = 2.07 95% CI = 1.65-2.60). By using bioinformatics tools, we found that rs115214213 may exist in the target region of miR-590-3p. Subsequently, we confirmed that miR-590-3p can repress CD44 expression and promote the apoptosis of CNE2 cells induced by cisplatin in vitro. After that, our transient transfection focusing on reporter gene expression modulated by CD44 3'UTR demonstrated that the presence of an rs13347T allele and rs115214213C allele led to greater transcriptional activity than the rs13347C allele and rs115214213T allele. Similarly, more CD44 expression was shown in minor allele carriers in our western blotting results. CONCLUSIONS All these findings suggest that CD44 rs13347C>T and rs115214213T>C polymorphisms may affect NPC development by improving CD44 expression.
Chemiluminescence Response of Human Leukocytes: Influence of Medium Components on Light Production

Light-producing reactions have been reported to occur after phagocytosis of opsonized particles by human polymorphonuclear neutrophils, eosinophils, and monocytes. Such chemiluminescence appears to be related to the generation of singlet oxygen, superoxide, and hydroxyl radicals, which have also been implicated as microbicidal agents. In examining the influences of various medium components on leukocyte chemiluminescence, we have observed that the amount of light measured is increased by addition of soluble protein, the amino acids tyrosine and tryptophane, or excess zymosan to the reaction medium. These agents appear to produce their effect not by increasing the rate of phagocytosis, but by providing substrate for secondary light-producing reactions. Polystyrene particles do not provide a suitable substrate for such secondary light-producing reactions. This is evidenced by the failure of ingested latex to stimulate high levels of chemiluminescence in the cellular system and their failure to augment light production in two noncellular chemiluminescent reactions. Some of the light generated in the cellular chemiluminescence response may derive from secondary reactions, which occur outside of the phagocyte. Support for this phenomenon is provided by two experiments. In one, addition of supplementary, nonopsonized zymosan to the reaction, after phagocytosis of opsonized zymosan is complete, resulted in an increased level of chemiluminescence. In another, addition of nonopsonized zymosan, together with latex particles, resulted in a significant increase in chemiluminescence. The results of the latter experiment also support our hypothesis that latex does not provide an appropriate substrate for secondary light-producing reactions. These observations suggest that leukocytes activated by phagocytosis generate electronically activated radicals which act intra- and extracellularly and that the amino acids tyrosine and trytophane may provide one substrate through which these agents act.
DNA Polymerase I of Mycobacterium tuberculosis

The highly conserved GXD sequence present in the Mycobacterium tuberculosis DNA polymerase I corresponds to a hinge region in the finger subdomain connecting M and N helices of Escherichia coli pol I. An examination of the crystal structures of pol I family polymerases reveals that the invariant aspartate of the hinge forms a salt bridge with the conserved arginine of the O-helix and an H-bond with Gln-708. To clarify the role of this region, we generated and characterized conserved and nonconserved mutant derivatives of this aspartate, the preceding glutamate and the Gln in TB pol I. For comparison, D732A mutein of pol I was also included. The muteins representing conserved aspartate (Asp-707 of TB pol I or Asp-732 of pol I) showed a strongK m (dNTP) effect and minor alteration inK d (DNA), with about 10–20-fold decrease in overall catalytic efficiency. The TB muteins, E706A and Q683A, have less pronounced deviations from the wild-type enzyme. Further examination of D707A of TB pol I showed no alteration in the processivity or the dideoxynucleotide sensitivity patterns. However, both TB pol D707A and homologous E. coli D732A failed to form a stable E·DNA·dNTP ternary complex. These results suggest that the aspartate in the hinge region is catalytically important and is required for dNTP binding and in the formation of a prepolymerase ternary complex.
Lactobacillus rhamnosus GG Dosage Affects the Adjuvanticity and Protection Against Rotavirus Diarrhea in Gnotobiotic Pigs

Objectives: The use of immunostimulatory strains of probiotics as adjuvants has been increasingly recognized as a promising approach in enhancing vaccine immunogenicity; however, dose effects of probiotic adjuvants are not well defined. In the present study, we examined dose effects of a commonly used probiotic strain, Lactobacillus rhamnosus GG (LGG), on immunomodulation with 2 different dosages. Methods: Neonatal gnotobiotic pigs were inoculated with 2 oral doses of attenuated human rotavirus (AttHRV) vaccines and fed with 5 doses (LGG5X; total 2.1 × 106 colony-forming units) or 9 doses (LGG9X; total 3.2 × 106 colony-forming units) of LGG, starting at 3 days of age. Results: Both LGG feeding regimens enhanced the protection rate of AttHRV vaccine against diarrhea on virulent human rotavirus challenge. LGG5X, but not LGG9X, significantly enhanced rotavirus-specific intestinal memory B-cell responses to AttHRV; LGG5X also significantly enhanced virus-specific intestinal immunoglobulin A (IgA) antibody-secreting cell responses. Both regimens significantly enhanced rotavirus-specific serum IgA antibody responses to AttHRV. They also enhanced rotavirus-specific interferon-&ggr;–producing effector/memory T-cell responses to AttHRV vaccine, with LGG9X being more effective than LGG5X, and both regimens downregulated CD4+CD25−FoxP3+ regulatory T (Treg) cell responses in most lymphoid tissues examined prechallenge and postchallenge and maintained the CD4+CD25+FoxP3+ Treg population in the ileum and intraepithelial lymphocyte postchallenge. LGG9X, however, did not significantly reduce total CD4+CD25−FoxP3+ Treg frequencies in the intestine and transforming growth factor-&bgr;–producing and interleukin (IL)-10–producing Treg frequencies in the blood. Conclusions: These results indicate that LGG at both dosages functioned as effective probiotic adjuvant for AttHRV vaccine, but different dosages differentially modulated immune responses to favor either the mucosal IgA response (LGG5X) or the T-cell response (LGG9X).
Delay-Dependent Robust  $H_{\infty}$ Filtering for Uncertain Discrete-Time Systems With Time-Varying Delay Based on a Finite Sum Inequality

This brief is concerned with delay-dependent robust Hinfin filtering for uncertain discrete-time systems with time-varying delay. The uncertainty is of convex polytopic type. By establishing a finite sum inequality based on quadratic terms, a new delay-dependent bounded real lemma (BRL) is derived. In combination with a parameter-dependent Lyapunov-Krasovskii functional, which allows the Lyapunov-Krasovskii matrices to be vertex dependent, the obtained BRL is modified into a new version to suit for convex polytopic uncertainties. Neither model transformation nor bounding technique for cross terms is involved. Based on the new BRL, the designed filter is provided in terms of a linear matrix inequality (LMI), which is easily solved by Matlab LMI toolbox. A numerical example is given to illustrate the effectiveness of the proposed method
Apoptosis as a Mechanism of Tissue Injury in Liver Allograft Rejection

Recent studies suggest that apoptosis is an important mechanism of cell death in the rejection of liver allografts and that infiltrating host lymphocytes mediate this process. The first section of this chapter addresses the cells and molecules that initiate the immune response following transplantation of a liver allograft. The recognition of donor alloantigens by infiltrating host lymphocytes stimulates a cascade of immune events which culminate in development of the effector cells that mediate tissue damage. Studies which demonstrate that apoptosis of hepatocytes and bile duct cells accompany allograft rejection are detailed in the second section of this chapter. The final section discusses the potential pathways which lead to apoptosis in liver allograft rejection. The contributions of the granule-exocytosis pathway, the Fas-mediated pathway, and cytokines to the induction of apoptosis in liver allografts are discussed. In addition, the concept that alloreactive graft infiltrating cells are deleted by apoptosis is presented. A further understanding of the mechanisms involved in apoptosis will lead to unique approaches toward the goal of achieving allograft tolerance.
Affective Dynamics in Psychopathology

We discuss three varieties of affective dynamics (affective instability, emotional inertia, and emotional differentiation). In each case, we suggest how these affective dynamics should be operationalized and measured in daily life using time-intensive methods, like ecological momentary assessment or ambulatory assessment, and recommend time-sensitive analyses that take into account not only the variability but also the temporal dependency of reports. Studies that explore how these affective dynamics are associated with psychological disorders and symptoms are reviewed, and we emphasize that these affective processes are within a nexus of other components of emotion regulation.
Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat).

The progression from ischemic injury to pannecrosis that occurs in the rat brain several hours after occluding a large artery may be partly attributable to a worsening of the circulation through the microvessels. The objective of this study was to quantitate selected structural changes involving astrocytes and endothelial cells within an area of focal brain ischemia created by the occlusion of a middle cerebral artery. The magnitude of these structural changes was correlated with alterations in the patency to a circulating macromolecule through the microvessels (< or = 15 mu in diameter) located within the territory of the occluded artery. One hundred eighty-five adult male Wistar rats had the right middle cerebral artery occluded after threading a nylon monofilament through the external carotid artery. Experiments were terminated by either cardiovascular perfusion or decapitation and immersion fixation at intervals ranging between 30 minutes and 7 days after the arterial occlusion. Randomly selected animals from each experimental subgroup were injected intravenously with horseradish peroxidase (molecular weight 44 kd) approximately 20 minutes before death. The progressive decline in the area fraction comprised by the vessels filled with horseradish peroxidase was preceded at 30 to 60 minutes by an increase in the surface area occupied (on a cross-section of a microvessel) by endothelial cells (both nucleus and cytoplasm). This was followed by an increase of 23.7% in the mean diameter of astrocytes nuclei and a decrease of approximately 35% in lumenal surface of the microvessels. These observations suggest that the occlusion of a large cerebral artery causes prompt swelling of endothelial cells and astrocytes; both of these early biological responses may interfere with erythrocyte circulation and oxygen delivery, which (after the arterial occlusion) are entirely dependent on the circulation provided by the collateral arterial connections. Through its interference with microvascular patency and oxygen delivery, cell swelling may influence the rate at which neurons become necrotic. In this model of brain infarct the number of necrotic neurons peaks approximately 72 hours after middle cerebral artery occlusion. (ABSTRACT TRUNCATED AT 400 WORDS)
Syndromic and non‐syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway

Common features such as elastic fibre destruction, mucoid accumulation, and smooth muscle cell apoptosis are co‐localized in aneurysms of the ascending aorta of various aetiologies. Recent experimental studies reported an activation of TGF‐β in aneurysms related to Marfan (and Loeys‐Dietz) syndrome. Here we investigate TGF‐β signalling in normal and pathological human ascending aortic wall in syndromic and non‐syndromic aneurysmal disease. Aneurysmal ascending aortic specimens, classified according to aetiology: syndromic MFS (n = 15, including two mutations in TGFBR2), associated with BAV (n = 15) or degenerative forms (n = 19), were examined. We show that the amounts of TGF‐β1 protein retained within and released by aneurysmal tissue were greater than for control aortic tissue, whatever the aetiology, contrasting with an unchanged TGF‐β1 mRNA level. The increase in stored TGF‐β1 was associated with enhanced LTBP‐1 protein and mRNA levels. These dysregulations of the extracellular ligand are associated with higher phosphorylated Smad2 and Smad2 mRNA levels in the ascending aortic wall from all types of aneurysm. This activation correlated with the degree of elastic fibre fragmentation. Surprisingly, there was no consistent association between the nuclear location of pSmad2 and extracellular TGF‐β1 and LTBP‐1 staining and between their respective mRNA expressions. In parallel, decorin was focally increased in aneurysmal media, whereas biglycan was globally decreased in aneurysmal aortas. In conclusion, this study highlights independent dysregulations of TGF‐β retention and Smad2 signalling in syndromic and non‐syndromic aneurysms of the ascending aorta. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs

The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.
Insights of Worsening Renal Function in Type 1 Cardiorenal Syndrome: From the Pathogenesis, Biomarkers to Treatment

Type-1 cardiorenal syndrome refers to acute kidney injury induced by acute worsening cardiac function. Worsening renal function is a strong and independent predictive factor for poor prognosis. Currently, several problems of the type-1 cardiorenal syndrome have not been fully elucidated. The pathogenesis mechanism of renal dysfunction is unclear. Besides, the diagnostic efficiency, sensitivity, and specificity of the existing biomarkers are doubtful. Furthermore, the renal safety of the therapeutic strategies for acute heart failure (AHF) is still ambiguous. Based on these issues, we systematically summarized and depicted the research actualities and predicaments of the pathogenesis, diagnostic markers, and therapeutic strategies of worsening renal function in type-1 cardiorenal syndrome.
Differential effects of Na+–K+ ATPase blockade on cortical layer V neurons

Sodium–potassium ATPase (‘Na+–K+ ATPase’) contributes to the maintenance of the resting membrane potential and the transmembrane gradients for Na+ and K+ in neurons. Activation of Na+–K+ ATPase may be important in controlling increases in intracellular sodium during periods of increased neuronal activity. Down‐regulation of Na+–K+ ATPase activity is implicated in numerous CNS disorders, including epilepsy. Although Na+–K+ ATPase is present in all neurons, little is known about its activity in different subclasses of neocortical cells. We assessed the physiological properties of Na+–K+ ATPase in fast‐spiking (FS) interneurons and pyramidal (PYR) cells to test the hypothesis that Na+–K+ ATPase activity would be relatively greater in neurons that generated high frequency action potentials (the FS cells). Whole‐cell patch clamp recordings were made from FS and PYR neurons in layer V of rat sensorimotor cortical slices maintained in vitro using standard techniques. Bath perfusion of Na+–K+ ATPase antagonists (ouabain or dihydro‐ouabain) induced either a membrane depolarization in current clamp, or inward current under voltage clamp in both cell types. PYR neurons were divided into two subpopulations based on the amplitude of the voltage or current shift in response to Na+–K+ ATPase blockade. The two PYR cell groups did not differ significantly in electrophysiological properties including resting membrane potential, firing pattern, input resistance and capacitance. Membrane voltage responses of FS cells to Na+–K+ ATPase blockade were intermediate between the two PYR cell groups (P < 0.05). The resting Na+–K+ ATPase current density in FS interneurons, assessed by application of blockers, was 3‐ to 7‐fold larger than in either group of PYR neurons. Na+–K+ ATPase activity was increased either through direct Na+ loading via the patch pipette or by focal application of glutamate (20 mm puffs). Under these conditions FS interneurons exhibited the largest increase in Na+–K+ ATPase activity. We conclude that resting Na+–K+ ATPase activity and sensitivity to changes in internal Na+ concentration vary between and within classes of cortical neurons. These differences may have important consequences in pathophysiological disorders associated with down‐regulation of Na+–K+ ATPase and hyperexcitability within cortical networks.
Diagnosis enhances, not impedes, boundaries of physical therapy practice.

Boissonnault and Bass (1-3) contribute an excellent and stimulating description of several "red flag" conditions that should alert physical therapists (PTs) to the presence of nonmechanical sources of pain. They provide an important reminder that pain has many etiologies, and that despite physician referral, patients may have visceral pathologies whose symptoms cannot be remediated by PTs. Their sobering anecdotes motivate us to take more careful histories and to make more precise patient observations. We believe, however, that when such "red flag" conditions appear to exist, the scope of physical therapy practice includes referral to other practitioners - be they MDs, PTs, RNs, or DPMs. We do not believe that scope of practice norms permit PTs ". to determine whether the symptoms are a result of.visceral pathology or other diseases". J Orthop Sports Phys Ther 1991;13(5):218-219.
Advances in Arrhythmia and Electrophysiology Premature Ventricular Contraction-Induced Cardiomyopathy A Treatable Condition

Premature ventricular contractions (PVCs) are early depolarizations of the myocardium originating in the ventricle. They are often seen in association with structural heart disease and represent increased risk of sudden death,1 yet they are ubiquitous, even in the absence of identifiable heart disease.1,2 They may cause troubling and sometimes incapacitating symptoms such as palpitations, chest pain, presyncope, syncope, and heart failure.3 Traditionally, they have been thought to be relatively benign in the absence of structural heart disease.4,5 Over the last decade, however, PVC-induced cardiomyopathy has been a subject of great interest and the evidence for this entity is rapidly emerging.
The use of the polymerase chain reaction to map CD4+ T cell epitopes

CD4+ T cells recognize processed exogenous antigen in the form of peptides bound to syngeneic major histocompatibility complex class II molecules on antigen‐presenting cells. We have developed a novel and convenient method to synthesize and map CD4+ T cell epitopes of cloned antigens using polymerase chain reaction (PCR)‐directed construction of genes expressing recombinant protein fragments. Unique restriction sites incorporated into the PCR primers were employed for the unidirectional cloning of gene fragments into a bacterial expression vector that can be induced to high‐level expression. The bacterial lysate could be used directly in T cell proliferation assays. Overlapping recombinant fragments spanning the entire protein were generated and tested. The length of the sequence containing the epitope was further reduced by utilizing PCR to generate 3′ truncations. Finally, a small number of overlapping peptides spanning a sequence of 39 amino acids were synthesized to identify a thirteen‐amino acid peptide epitope within chicken transferrin that stimulates the T helper cell clone D10.G4. 1. PCR‐directed construction of fragments of antigen allows for optimal design of strategies for the mapping and analysis of CD4+ T cell epitopes.
IPMDS‐Sponsored Scale Translation Program: Process, Format, and Clinimetric Testing Plan for the MDS‐UPDRS and UDysRS

We present the methodology and results of the clinimetric testing program for non‐English translations of International Parkinson and Movement Disorder Society (MDS)–sponsored scales. The programs focus on the MDS revision of the UPDRS (MDS‐UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The original development teams of both the MDS‐UPDRS and UDysRS envisioned official non‐English translations and instituted a rigorous translation methodology. The formal process includes five core steps: (1) registration and start‐up; (2) translation and independent back‐translation; (3) cognitive pretesting to establish that the translation is clear and that it is comfortably administered to and completed by native‐speaker raters and patients; (4) field testing in the native language using a large sample of Parkinson's disease patients; and (5) full clinimetric testing. To date, the MDS‐UPDRS has 21 active language programs. Nine official translations are available, having completed all phases successfully, and the others are in different stages of development. For the UDysRS, 19 programs are active, with three official translations now available and the rest in development at different stages. Very few scales in neurology and none in movement disorders have fully validated translations, and this model may be adopted or modified by other scale programs to allow careful validation of translations. Having validated translations allows for maximal homogeneity of tools utilized in multicenter research or clinical trial programs.