Miracle-dz/UniFAR-FTUs huggingface dataset:
Study of Treg FOXP3 in childhood bronchial asthma in relation to corticosteroid therapy

Background: T cells are considered the main cells responsible for production of suppressive cytokines, and play a key role in balancing the immune responses to maintain the peripheral tolerance against allergens. Objective: The present study investigates T regulatory (Treg) forkheadwinged helix protein 3 FOXP3 expression in childhood asthma and its relation to corticosteroid therapy. Methods: In this case control study, Treg FOXP3 was measured in blood of 60 children using real time polymerase chain reaction (RT-PCR) technique. Two asthmatic groups were included, one on corticosteroid therapy (20 patients) and the other not on corticosteroid treatment (20 patients). They were compared to 20 healthy children as controls. Results: FOXP3 concentration was significantly elevated in asthmatic patients (90 ± 77.4) compared to healthy children (12.844 ± 10.6) (p= 0.000). FOXP3 was significantly more elevated in asthmatics on corticosteroids (161.158 ± 63.9) than steroid naive asthmatics (36.038 ± 23.4) (p=0.000). Levels of Treg FOXP3 in asthmatics with inhaled corticosteroids (mean 151.16 ± 53.79) were almost similar to FOXP3 in asthmatics with systemic corticosteroids (161.49±72.5) (p>0.05). FOXP3 levels did not differ with smoking, asthma severity or disease control and did not correlate with age, FEV1, blood lymphocytes percentage or eosinophils percentage. Conclusion: Asthmatics have increased expression of FOXP3, and corticosteroid therapy –whether oral or inhaled - enhances FOXP3 expression. Keywords: FOXP3, Treg, Corticosteroids, Bronchial asthma, Transcription factors, Cytokines Egypt J Pediatr Allergy Immunol 2012;10(1):39-43.
Cerebral Effect of Intratracheal Aerosolized Surfactant Versus Bolus Therapy in Preterm Lambs

Objective:Aerosolization has been proposed as a useful alternative to rapid intratracheal instillation for the delivery of exogenous surfactant in neonatal respiratory distress syndrome. However, there is a lack of information regarding the likely safety of this new therapeutic approach for the neonatal brain. We aimed to compare the cerebral effects of aerosolized versus bolus surfactant administration in premature lambs with respiratory distress syndrome. Design:Prospective randomized study. Setting:BioCruces Institute Animal Research Facility. Subjects:Fourteen intensively monitored and mechanically ventilated preterm lambs. Interventions:Preterm lambs were randomly assigned to receive intratracheal aerosolized surfactant or bolus surfactant. Brain hemodynamics (cerebral and regional cerebral blood flow) and cerebral oxygen metabolism (cerebral oxygen delivery, cerebral metabolic rate of oxygen, and oxygen extraction fraction) were measured every 30 minutes for 6 hours. We also performed cerebral biochemical and histological analysis. Measurements and Main Results:In preterm lambs with respiratory distress syndrome, cerebral blood flow, regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate of oxygen increased significantly in the bolus surfactant group during the first 5 minutes, without changes in cerebral oxygen extraction fraction. By 60 minutes, all parameters had decreased in both groups, cerebral blood flow and regional cerebral blood flow (in inner and cerebellum brainstem regions) remaining higher in the bolus surfactant than in the aerosolized surfactant group. Overall, the impact of aerosol surfactant was not significantly different to that of bolus surfactant in terms of cerebral necrosis, edema, inflammation, hemorrhage, infarct, apoptosis, or oxidative stress. Conclusions:In preterm lambs with severe respiratory distress syndrome, aerosol surfactant administration seems to be as safe as bolus administration, showing more stable cerebral hemodynamics and cerebral oxygen metabolism to the same dose of surfactant administered as a standard bolus.
Selective lesioning of the cat pre‐Bötzinger complex in vivo eliminates breathing but not gasping

1 To examine the functional importance of the pre‐Bötzinger complex for breathing we micro‐injected, under in vivo conditions, the calcium channel blocker ω‐conotoxin GVIA and the sodium channel blocker tetrodotoxin (TTX) into the ventrolateral medulla of adult cats, while monitoring respiratory rhythmic motor output in the phrenic nerve. 2 ω‐Conotoxin GVIA caused a highly localized synaptic ablation by blocking presynaptic N‐type calcium channels. When injecting 5–60 fmol ω‐conotoxin GVIA unilaterally, the amplitude of phrenic nerve activity decreased bilaterally and sometimes disappeared, indicating central apnoea. These effects were reversible and could only be induced in a very localized area of the pre‐Bötzinger complex. By injecting ω‐conotoxin GVIA several times during an experiment and analysing the areas where injections affected respiratory activity, it was possible to map exactly the anatomical extent of the area critical for respiratory rhythm generation. 3 Following the precise localization of the pre‐Bötzinger complex with ω‐conotoxin GVIA, we injected TTX to induce an irreversible inactivation of this region. TTX injected unilaterally into the pre‐Bötzinger complex irreversibly reduced the amplitude of phrenic nerve activity. Bilateral TTX injections eliminated respiratory rhythmic activity, causing a persistent central apnoea. 4 After bilateral lesioning of the pre‐Bötzinger complex, it was still possible to induce gasping during hypoxia or asphyxia, indicating that respiration and gasping are generated by two different neuronal networks. 5 We propose that ω‐conotoxin GVIA as employed in this study to investigate the functional role of the pre‐Bötzinger complex can also be used as a general pharmacological approach to map other neuronal networks. We call this the ‘ω‐conotoxin GVIA tracing’ method.
Tolls: you pay them on the way in and on the way out!

Toll-like receptors (TLRs) are important components of the innate immune system , the evolutionary ancient response system consisting of pattern recognition proteins that recognize pathogen associated molecular patterns (PAMPs). TLRs are a series (10 in humans) of cell surface or intracellular receptor proteins that contain signaling motifs that are structurally similar to the mammalian interleukin (IL)–1 receptor and the Toll protein of insects. In mammals, TLRs function by recognizing viruses, bacteria, fungi, and parasites on the basis of their PAMPs, and then activating cells to produce cytokines including interferon (IFN) and inflam-matory cytokines such as IL-1 and tumor necrosis factor that may either lead to local or systemic inflammation (reviewed in [1]). TLRs also activate the adaptive immune responses (B and T cells). As a result , they are critical to the initial host response to infection. TLR4 was originally described as the cell surface receptor that signaled the binding of lipopolysaccharide and was therefore responsible for septic shock after infection with gram-negative organisms. TLR2 was initially shown to be important in the sepsis syndrome caused by gram-positive organisms. In this issue of the Journal, Bochud et al. [2] have noted an association between polymorphisms in TLR2 and recurrences of herpes simplex virus type 2 (HSV-2) infection. This type of study brings us closer to understanding how genetic predispositions define how one will respond to an infectious challenge. If, in the future, we can use genetic polymorphisms to predict responses to pathogens, this would help in understanding and therefore potentially altering the course of an infectious disease. The concept that one could predict an individual's response to an infectious agent on the basis of his/her genetic predisposition is the " holy grail " of molecular genetics. If this is correct, it opens the door to new diagnostic and therapeutic approaches. For example, one might selectively vaccinate those who are likely to develop overwhelming disease to try to shift their im-munologic profile from a Th2 response pattern (characterized by high levels of an-tibodies and IL-10 production) to a Th1 response (characterized by cytolytic T cell responses and IFN-g production). A particular TLR polymorphism might predict an inability to respond to a conventional dose of vaccine and mandate a different approach (perhaps the use of an adjuvant or another approach to prevention). The interesting question is, " how does a polymorphism in a pattern recognition protein affect the pathogenesis of an infectious …
Autonomic nervous function during whole-body cold exposure before and after cold acclimation.

INTRODUCTION Cold habituation could affect sympatho-vagal balance, which modulates cold stress responses. The study examined cardiovascular autonomic function at the sinus node level during controlled breathing and while undertaking isometric exercise during whole-body cold exposure before and after cold acclimation. METHODS There were 10 male subjects who were exposed to control (25 degrees C) and cold (10 degrees C) environments for 2 h on 10 successive days in a laboratory. Time and frequency domain heart rate variability (HRV) in terms of root mean square of successive differences in RR intervals, total, high, and low frequency power were determined from controlled breathing at the beginning and end of cold acclimation. Heart rate and blood pressure during an isometric handgrip test (30% MVC for 3 min) were recorded at the beginning and end of cold acclimation. Catecholamines (NE and E), mean skin (Tsk), and rectal temperatures (Trect) were measured. RESULTS Acute cold exposure increased total (36%), low (16%), and high frequency power (25%) and RMSSD (34%). Cold acclimation resulted in higher Tsk (0.6 degrees C) and lower NE (24%) response in cold. The cold-induced elevation in high frequency power became significant after cold acclimation, while other HRV parameters remained unchanged. A smaller increase in heart rate and blood pressure occurred at 10 degrees C during the handgrip test after cold acclimation. DISCUSSION Cold exposure increased sympathetic activity, which was blunted after cold acclimation. Parasympathetic activity showed a minor increase in cold, which was enhanced after cold acclimation. In conclusion, cold habituation lowers sympathetic activation and causes a shift toward increased parasympathetic activity.
5 Cartilage Calcification

Nineteenth century histologist Ranvier discovered the point of ossification and the calcification of cartilage as observed in embryos (Ranvier, 1875). By skillfully using simple methods such as hand-cutting with a razor, or with a lead-screw microtome of his own invention (still marketed as the Ranvier hand microtome), and chromic acid and carmine to stain, he observed the deposition of calcareous salts around cartilage capsules. Ranvier described chondrocytes and their distinctive arrangement in series to yield larger capsules. He observed how calcified capsules open into one another to form anfractuous cavities that become the earliest marrow spaces, and wondered what determines the resorption of the walls. After injecting Prussian blue to mark vessels in growing animals, he described wall destruction as proceeding selectively in the direction of vessel growth (Figure 1a). Soon after, Schäfer described how to prepare fresh or fixed cartilage sections, and recommended the use of osmic acid, silver nitrate and gold chloride (Schäfer, 1897). He then (Schäfer, 1907) published a series of four colour drawings comprising all the stages of ossification (Figure 1b); these drawings have been a source of inspiration for all later histology textbooks (see, for instance, Figure 1 c). Subsequent methodological advances in microscopy and microtomy allowed confirmation of all the early observations. In the first third of the twentieth century histology textbooks by Cajal, Bouin, Möllendorff, Maximow & Bloom, Cajal & Tello, Levi and Di Fiori, described endochondral ossification, the ossification centre, and the growth plate as we know them today. Interestingly, some doubts persisted about hypertrophic chondrocytes. Using silver reducing methods, Cajal and Tello described the well-developed Golgi apparatus of hypertrophic chondrocytes, and how it is reduced and fragmented in the last row of cells (Figure 1d), as well as the vacuolization of chondrocytes that makes these cells hypertrophic (Figure 1e).
Circulatory adjustments of voluntary muscle in anemia.

Simultaneous measurements of the blood flow through the human forearm and of the arteriovenous oxygen difference of forearm blood have shown that in moderate anemia the need for oxygen was met by an increase in the arteriovenous oxygen difference without increase in blood flow. When the hemoglobin fell below 4 gm. % the blood flow rose. In subjects in whom the blood flow had increased, the venous oxygen saturation was below 15%. Cardiac output has been shown to increase when the hemoglobin falls below 8 gm. %. It is concluded that the initial increase in heart output is not due to ischemia of voluntary muscle but is required for maintaining the metabolism of the brain and the heart itself. Submitted on July 3, 1958
Identification of a high-affinity binder for estradiol and a low-affinity binder for testosterone in Coccidioides immitis

Coccidioides immitis cytosol contains a specific estrogen binder with kinetic characteristics (Kd = 2.1 X 10(-8) to 3.7 X 10(-8) M; n = 0.5 to 1.56 pmol/mg of protein) appropriate for interaction with levels of estrogen encountered during pregnancy. The Kd of a separate androgen binder (ca. 10(-7) M) is probably too low to allow interaction with physiological levels of testosterone.
Retinoic acid embryopathy: report of two cases associated with the use of isotretinoin

Received on January 07, 2008; accepted on January 28, 2008. AbstrAct The authors report two cases associated with the use of isotretinoin before or during the gestational period, with its characteristic aspects and variations, of one male and one female child. This report aims at raising the awareness of medical professionals about the possible risk of isotretinoin administration to fertile-aged women considering the severity of malformations in the different systems of the human body.
Hyperosmolarity and Benzalkonium Chloride Differently Stimulate Inflammatory Markers in Conjunctiva-Derived Epithelial Cells in vitro

Tear hyperosmolarity is known to cause ocular surface inflammation in dry eye syndrome. Benzalkonium chloride (BAK), an eyedrop preservative, is known to induce dry eye in long-term-treated patients. Analyzing the modulation of the proinflammatory potential of hyperosmolarity in the presence of BAK on the conjunctiva could give new insights into the effect of this preservative on the disease. In a hyperosmolar model on a conjunctiva-derived cell line, and in the presence of BAK, we evaluated key inflammatory markers [CCL2, IL-8, IL-6, macrophage migration inhibitory factor (MIF) and intercellular adhesion molecule (ICAM)-1] as well as the osmoprotectant element nuclear factor of activated T cells (NFAT)5 using ELISA, RT-qPCR or immunofluorescence staining. Hyperosmolarity highly stimulated CCL2 and NFAT5 in these cells. BAK alone only increased IL-6 expression. The stress-combined condition stimulated CCL2, NFAT5, MIF and IL-8 secretion. ICAM-1 was not modulated by any of the conditions tested. In this model, hyperosmolarity and BAK induced the release of different proinflammatory mediators, and, when combined, they lead to the release of additional inflammatory cytokines. This in vitro study highlights the importance of avoiding long-term ophthalmic treatments containing BAK, as tear film hyperosmolarity can be a result of its detergent action.
Accumulation of Inorganic Polyphosphate in phoU Mutants of Escherichia coli and Synechocystis sp. Strain PCC6803

ABSTRACT The biological process for phosphate (Pi) removal is based on the use of bacteria capable of accumulating inorganic polyphosphate (polyP). We obtained Escherichia coli mutants which accumulate a large amount of polyP. The polyP accumulation in these mutants was ascribed to a mutation of the phoU gene that encodes a negative regulator of the Pi regulon. Insertional inactivation of the phoU gene also elevated the intracellular level of polyP in Synechocystis sp. strain PCC6803. The mutant could remove fourfold more Pi from the medium than the wild-type strain removed.
Understanding and Management of Browning in Fresh Whole and Lightly Processed Fruits

Browning is the result of appearance of dark colored pigments formed by enzymatic and non enzymatic reactions. In this review AA, first overview the biochemistry of browning and fruits response and protection, successively touch the topic in the lightly processed fruits. Non enzymatic reaction is mainly due to Maillard reaction compounds in which concentration of amino acid (nitrogen supply) and sugars content plays the important role. Enzymatic reaction is driven mainly by polyphenols oxidase (PPO) but PPO is not the only factor, indeed the decline in the concentration of some browning activators, such as fatty acids and organic acids, and a decrease in phenolic substrate synthesis with increasing ripening, could be even important. Other enzymes are involved in the browning process, more or less intensively, depending on the product. The action of PPO as well as the other enzymes is favoured by membrane degradation which permits the contact between the enzymes and the substrate (PPO and phenols). Thus, every factor affecting membrane layers stability will result in a browning symptom. In some cases, anoxic conditions for short time prevent the appearance of browning because of reduction energy available, or because of the formation of ethanol and acetaldehyde. Carbon dioxide can inhibit browning but it can accelerate. 1-methylcyclopropene, ethylene action inhibitor, can inhibit superficial scald in apple but even provokes browning (greyish peel) in banana. In conclusion there is no prevention action against browning which can be recommended totally safe because the system is very complex and affected from many factors. _____________________________________________________________________________________________________________
Studies on platelet proteins. IV. Some physical and chemical properties of thrombosthenin.

The contractile platelet protein thrombosthenin has been isolated with butanol and purified further by repeated precipitation and gel filtration. Thrombosthenin thus isolated shows all the typical properties of this protein as reported in the literature. 1 M NaCl-tris, pH 7.2 has been found to be a better solvent than 0.6 M KCl as far as stability, resolution and aggregation of the protein are concerned. In the ultracentrifuge, 0.7 per cent thrombosthenir in 0.6 M KCl shows three hypersharp boundaries with sedimentation coefficients of 36 S, 56 S and 83 S. However, at low protein concentration only the 36 S boundary is observed. In 1 M NaCl, all these components break down producing a single kinetic unit of 18 S which dissociates further to 7 S. The 7 S component retains the ATP-sensitivity typical of thrombosthenin, suggesting it to be the monomeric unit of this protein. A similar hypersharp boundary with similar sedimentation coefficient to purified thrombosthenin has been noted in platelet ghosts solubilized in presence of detergent. A combination of sedimentation and viscosity data leads to an approximate molecular weight 8.9 x 10 5 for thrombosthenin.
Reaction of mast cell proteases tryptase and chymase with protease activated receptors (PARs) on keratinocytes and fibroblasts

Protease activated receptors (PARs) compose a family of G protein signal transduction receptors activated by proteolysis. In this study, the susceptibility of PARs expressed on human keratinocytes and dermal fibroblasts to the human mast cell proteases tryptase and chymase was evaluated. PAR activation was measured by monitoring cytosolic [Ca2+] in cells loaded with the fluorescent Ca2+ probe Fura‐2. Tryptase produced transient cytosolic Ca2+ mobilization in keratinocytes, but not in fibroblasts. Ca2+ mobilization in keratinocytes required enzymatically active tryptase, demonstrated desensitization, and was blocked by pretreatment of cells with the PAR‐2 peptide agonist SLIGKV, trypsin, or the phospholipase inhibitor U73122. Heparin, a GAG that binds to tryptase, stabilizing its functional form, also inhibited tryptase‐induced Ca2+ mobilization. The maximal response elicited by tryptase was smaller than that observed upon treatment of keratinocytes with trypsin, a known activator of PAR‐2, and keratinocytes made refractory to tryptase by pretreatment with the protease remained responsive to trypsin. Pretreatment of keratinocytes with thrombin, an activator of PAR‐1 and ‐3 (thrombin receptors), had no detectable effect on the tryptase or trypsin responses. These data suggest that in keratinocytes tryptase may be activating a subpopulation of PAR‐2 receptors. Treatment of keratinocytes or fibroblasts with human chymase did not produce Ca2+ mobilization, nor did it affect Ca2+ mobilization produced by trypsin. However, chymase pretreatment of fibroblasts rapidly inhibited the ability of these cells to respond to thrombin. Inhibition was dependent on chymase enzymatic activity and was not significantly affected by the presence of heparin. This finding is consistent with studies indicating that PAR‐1 may be susceptible to proteases with chymotrypsin‐like specificity. These results suggest that the proteases tryptase and chymase secreted from mast cells in skin may affect the behavior of surrounding cells by the hydrolysis of PARs expressed by these cells. J. Cell. Physiol. 176:365–373, 1998. © 1998 Wiley‐Liss, Inc.
100-km Standard SMF transmission of Japanese digital terrestrial television broadcasting signal with EDFA and Optical single sideband modulation

Japanese digital terrestrial television broadcasting signal was successfully conveyed by optical single sideband modulation light through 100-km standard single mode fiber, using an EDFA as a repeater. In this experiment, practically used broadcasting radio wave was employed and six channels were modulated at the same time. Simple direct detection was used at the receiver side, while the LiNbO3 based external modulator was used in the transmitter.
Relation between Plasma PAI Activity and Adipsin Levels

The analysis of coagulation parameters (Table 1) showed decreased activities of antithrombin III (AT III), protein C (PC) and plasminogen, respectively. Corresponding antigen levels were found within normal ranges indicating type II deficiencies of both coagulation inhibitors and plasminogen. Mutations as one possible cause of type II deficiencies were ruled out by sequencing of PCR amplified PCand ATIII-cDNA making a post-translational defect in protein processing most likely. Protein S parameters and the anticoagulant response to activated PC (APC-resistance) were found within normal ranges. In summary, the glycosylation defect in our patient with CDG-syndrome of type I caused severe antithrombin IIIand protein C-deficiencies clinically associated with bilateral deep vein thrombosis. The moderate plasminogen deficiency might explain the poor response to t-PA lysis. These data indicate that not only bleeding but also thrombosis can be a problem in patients with CDG-syndrome. Furthermore, the state of thrombophilia might explain stroke-like episodes being reported in other patients with CDG-syndrome (4,5).