Miracle-dz/UniFAR-FTUs huggingface dataset:
The Origin of TH2 Responses

The adaptive immune response to helminth infection and allergens is stimulated by cytokines secreted by innate immune cells. Helper T lymphocytes (TH cells) have multiple functions during human immune responses, including stimulating B cells, the “help” needed to spur antibody production. Naïve TH precursor cells give rise to four functionally distinct subsets that can be further divided into subtypes or regulated states. Once the first two TH subsets were recognized—TH1 and TH2 cells (1)—the obvious question became: How does the immune system decide which response to make? Recent reports present an important advance in understanding the origins of TH2 responses and mechanisms of immune recognition of two medically important classes of antigens: helminth parasites and allergens.
The Bohr effect on the reaction of carbon monoxide with fully oxygenated haemoglobin.

1. The rate at which CO displaces O2 from its combination with haemoglobin in solution, has been measured spectrophotometrically, using a rapid‐mixing stopped‐flow technique. 2. In the presence of CO2, the reaction proceeds by a unimolecular dissociation, with a rate constant r. 3. The relationship of the reciprocal of r to the ratio PO2/PCO is nonlinear, and a different curve is obtained at each CO concentration. 4. Measurements were made of the rate of the reaction when the pH was varied, with constant or varying PCO2. In both situations the value of r was found to have a miximum, for a given PO2/PCO ratio and CO cencentration, at pH 7.2. 5. An analysis of these results suggest that the Bohr effect, of pH and PCO2, is a dynamic equilibrium between four stable tertiary states of each of the alpha and beta chains. Each intermediatory complex has different rate constants for CO and O2.
Slow Gastric Emptying in Type I Diabetes: Relation to Autonomic and Peripheral Neuropathy, Blood Glucose, and Glycemic Control

OBJECTIVE To investigate whether autonomic neuropathy or hyperglycemia plays a crucial etiological role in gastric retention of ingesta frequently found in type I diabetic patients. RESEARCH DESIGN AND METHODS We investigated the gastric emptying of a radiolabeled semisolid 1,168 kJ meal in 38 female and 45 male patients (age 18–75 years; illness duration 3–46 years). None took drugs affecting gastrointestinal motility. Fasted patients underwent tests of cardiovascular autonomic and peripheral nerve function. Blood glucose levels were determined before and after the scintigraphic recording of gastric emptying. RESULTS The percentage of meal remaining in the stomach at the end of the 50-min recording time was related significantly to the patients' degree of cardiovascular autonomic neuropathy [r (81) = 0.235, P < 0.028] but not to their degree of peripheral neuropathy, preprandial blood glucose level, HbA1c indicative of glycemic control, diabetes duration, and age. The patients' mean residual percentage of meal was significantly > that of 48 healthy subjects, that is, 71.1 ± 15.1 vs. 53.5 ± 13.1% [means ± SD; t (129) = 6.48, P < 0.0001]. The healthy individuals' mean residual percentage + 2 SD was exceeded in 22 patients. CONCLUSIONS Slow gastric emptying in patients with type I diabetes seems related to the degree of autonomic neuropathy but not to peripheral neuropathy, actual blood glucose, and glycemic control.
Effects of age upon the mobility of human finger joints.

Fewmeasurements havebeenmadeofthefrictional forces within living joints. Barnett and Cobbold(1962) recorded thatthecoefficient of friction atthedistal interphalangeal joint ofthe middle finger insixhealthy adults could beaslowas 00075, afigure ofthesameorder asthat inexcised joints (Jones, 1936; Charnley, 1959). Rydell (1965) measured, inapatient fitted withahipprosthesis, thecoefficient offriction between theartificial femoral hipandtheintact acetabulum; hegavea figure 0021± 0-0014. Thepresent paperisconcerned withthevariation observed inthecoefficient offriction, asreflected byjoint mobility, among individuals ofdifferent ages.
Regulation of ground squirrel Na+K+-ATPase activity by reversible phosphorylation during hibernation.

Maintenance of skeletal muscle energy status during hibernation in ground squirrels, Spermophilus lateralis, was accompanied by a decrease in Na+K+-ATPase pump activity. Energy charge was maintained (0.89) during hibernation at the expense of total adenylates (decreased by 41%). Muscle Na+K+-ATPase activity was 9.1 U/mg protein in euthermic controls but decreased by 60% during hibernation. Enzyme activity was similarly suppressed in vitro when extracts of control muscle were incubated with ATP plus second messengers of protein kinases A, G or C whereas stimulation of protein phosphatases in muscle extracts from hibernators increased Na+K+-ATPase activity. Additional studies confirmed that suppression and reactivation of the enzyme in euthermic muscle extracts can be achieved with protein kinase A and alkaline phosphatase treatments, respectively, and indicated that phosphorylation changes the ATP dependency of the enzyme. Thus, hibernation-induced suppression of Na+K+-ATPase activity in muscle and other organs of ground squirrels, which is a key part of the overall suppression of metabolic rate that constitutes torpor, appears to be regulated via reversible protein phosphorylation.
SKIP, a CBF1-Associated Protein, Interacts with the Ankyrin Repeat Domain of NotchIC To Facilitate NotchIC Function

ABSTRACT Notch proteins are transmembrane receptors that mediate intercell communication and direct individual cell fate decisions. The activated intracellular form of Notch, NotchIC, translocates to the nucleus, where it targets the DNA binding protein CBF1. CBF1 mediates transcriptional repression through the recruitment of an SMRT-histone deacetylase-containing corepressor complex. We have examined the mechanism whereby NotchIC overcomes CBF1-mediated transcriptional repression. We identified SKIP (Ski-interacting protein) as a CBF1 binding protein in a yeast two-hybrid screen. Both CBF1 and SKIP are highly conserved evolutionarily, and the SKIP-CBF1 interaction is also conserved in assays using the Caenorhabditis elegans andDrosophila melanogaster SKIP homologs. Protein-protein interaction assays demonstrated interaction between SKIP and the corepressor SMRT. More surprisingly, SKIP also interacted with NotchIC. The SMRT and NotchIC interactions were mutually exclusive. In competition binding experiments SMRT displaced NotchIC from CBF1 and from SKIP. Contact with SKIP is required for biological activity of NotchIC. A mutation in the fourth ankyrin repeat that abolished Notch signal transduction did not affect interaction with CBF1 but abolished interaction with SKIP. Further, NotchIC was unable to block muscle cell differentiation in myoblasts expressing antisense SKIP. The results suggest a model in which NotchIC activates responsive promoters by competing with the SMRT-corepressor complex for contacts on both CBF1 and SKIP.
Preterm sucking behaviour and later neurodevelopment

the relatively short period examined. Wider evidence on longer-term trends in CP prevalence and survival is more mixed. The risk of CP is very strongly related to gestation at delivery. Trends in overall prevalence of CP are therefore likely to reflect complex underlying trends in the proportion of infants born preterm, the subsequent survival of these infants, and gestation-specific CP risk. Long-term trends in prematurity rates are not readily available for England and Wales; however, data for Scotland show a consistent increase over recent decades in the proportion of live births that were born preterm, from around 6% in the early 1980s to around 8% currently (http://www.isdscotland.org/ Health-Topics/Maternity-and-Births/Births/). As survival of infants born preterm has also increased, a constant overall CP prevalence would suggest that risk among these infants may be falling over time. Thinking more broadly about the ‘preventability’ of CP, limiting preterm birth is critical but challenging given current knowledge. Other measures such as prevention of antenatal and postnatal infections and Rhesus isoimmunization, mitigation of multiple pregnancy risk in assisted reproduction, and neuroprotective measures for high-risk neonates (such as antenatal magnesium and postnatal therapeutic cooling) all remain important. Improved monitoring of fetal well-being and optimal delivery are also important although can drive up iatrogenic prematurity. The estimated numbers of children living with CP provided by Glinianaia et al. have been derived assuming the prevalence and survival observed in the North of England apply equally to all regions of England and Wales. Similarly, given the lack of a secular trend in observed prevalence or survival, the anticipated increase in the number of children with CP simply reflects historical and projected trends in live birth numbers. These assumptions could be challenged but are likely to be sufficient for service planning purposes. Overall, the key message arising from the paper by Glinianaia et al. is that, austerity and service cuts notwithstanding, the need for robust, integrated services for children (and their families) with complex needs is unlikely to diminish in the short to medium term. Regardless of advances in prevention, there will always be children with significant impairment and disability, and how we collectively organize and deliver services to meet their needs will remain a measure of our society.
The possible role of quinate in the mode of action of glyphosate and acetolactate synthase inhibitors.

BACKGROUND The herbicide glyphosate inhibits the biosynthesis of aromatic amino acids by blocking the shikimate pathway. Imazethapyr and chlorsulfuron are two herbicides that act by inhibiting branched-chain amino acid biosynthesis. These herbicides stimulate secondary metabolism derived from the aromatic amino acids. The aim of this study was to test if they cause any cross-effect in the amino acid content and if they have similar effects on the shikimate pathway. RESULTS The herbicides inhibiting two different amino acid biosynthesis pathways showed a common pattern in general content of free amino acids. There was a general increase in total free amino acid content, with a transient decrease in the proportion of amino acids whose pathways were specifically inhibited. Afterwards, an increase in these inhibited amino acids was detected; this was probably related to proteolysis. All herbicides caused quinate accumulation. Exogenous application of quinate arrested growth, decreased net photosynthesis and stomatal conductance and was ultimately lethal, similarly to glyphosate and imazethapyr. CONCLUSIONS Quinate accumulation was a common effect of the two different classes of herbicide. Moreover, exogenous quinate application had phytotoxic effects, showing that this plant metabolite can trigger the toxic effects of the herbicides. This ability to mimic the herbicide effects suggests a possible link between the mode of action of these herbicides and the potential role of quinate as a natural herbicide.
Identification and Treatment of Women with Hyperglycaemia Diagnosed During Pregnancy Can Significantly Reduce Perinatal Mortality Rates *

Summary: We wished to determine whether gestational diabetes was associated with an increased perinatal mortality rate, and to investigate the cause for the observed increase in the incidence of gestational diabetes. We therefore reviewed the results of glucose tolerance tests and pregnancy outcome in 116,303 pregnancies, 1971–1994, at the Mercy Hospital for Women. The main outcome measurements were the presence or absence of gestational diabetes, and perinatal mortality. Over the entire period of the study, gestational diabetes was associated with an increased risk of perinatal mortality (Mantel‐Haenszel adjusted odds ratio 1.53, 95% CI 1.13‐2.06, p=0.0069). Women with gestational diabetes that was only diagnosed retrospectively had a higher perinatal mortality rate than their contemporaries with normal glucose tolerance (OR 2.31,95% CI 1.37‐3.91, p=0.0025). Women in whom a glucose tolerance test was not performed continued to have a higher perinatal mortality rate than women who were tested (adjusted OR 2.21,95% CI 1.56‐3.12, p<0.00001). There has been an increase in the prevalence of gestational diabetes from 2.9% to 8.8%. Some of this is due to changes in population characteristics (increases in maternal age, obesity and proportion from South‐East Asia), but there was still an independent increase over time. We conclude that identification and treatment of women with gestational diabetes can reduce perinatal mortality rates. Similarly to diabetes mellitus in the total population, the prevalence of gestational diabetes has increased over time.
Topors Functions as an E3 Ubiquitin Ligase with Specific E2 Enzymes and Ubiquitinates p53*

The human topoisomerase I- and p53-binding protein topors contains a highly conserved, N-terminal C3HC4-type RING domain that is homologous to the RING domains of known E3 ubiquitin ligases. We demonstrate that topors functions in vitro as a RING-dependent E3 ubiquitin ligase with the E2 enzymes UbcH5a, UbcH5c, and UbcH6 but not with UbcH7, CDC34, or UbcH2b. Additional studies indicate that a conserved tryptophan within the topors RING domain is required for ubiquitination activity. Furthermore, both in vitro and cellular studies implicate p53 as a ubiquitination substrate for topors. Similar to MDM2, overexpression of topors results in a proteasome-dependent decrease in p53 protein expression in a human osteosarcoma cell line. These results are similar to the recent finding that a Drosophila topors orthologue ubiquitinates the Hairy transcriptional repressor and suggest that topors functions as a ubiquitin ligase for multiple transcription factors.
Synergistic Effect of Essential Amino Acids and Glucose upon Insulin Secretion in Man

Arginine, leucine, or histidine, and glucose were each administered intravenously, in 30-gm. amounts on separate occasions to the same healthy subjects. Each of the amino acids and glucose in these same amounts were administered also as mixtures. Synergism in the stimulation of the release of insulin was demonstrated when the sum of the increases in plasma insulin which resulted from the separate administrations of an amino acid and glucose was exceeded by that obtained when they were administered as a mixture. A synergistic effect was exerted by each of the three amino acid-glucose combinations; it was greatest with arginine and glucose and least with histidine and glucose. Synergism probably results from the effects of these stimuli upon the pancreatic beta cell; it is not dependent upon humoral gastrointestinal factors released after the ingestion of these nutrients.
Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature

Recombinant human erythropoietin (rHuEPO) is an effective treatment for the anaemia that occurs secondary to various conditions, but its role in myelofibrosis with myeloid metaplasia (MMM) is not well established. rHuEPO, at an initial dose of 10 000 U thrice a week, was given to 20 patients with MMM and anaemia. Complete response (CR) was defined as transfusion cessation with normal haemoglobin (Hb) levels and partial response (PR) as a transfusion decrease ≥50% and Hb > 10 g/dl maintained for at least 8 weeks. Nine patients (45%) showed a favourable response to treatment, including four CR and five PR, four of whom have maintained their response at a median follow‐up of 12·5 months (range: 4–21 months) from the start of treatment. The pretreatment factors associated with a favourable response were lack of transfusion requirement (P = 0·002) and higher Hb at start treatment of (P = 0·01). An analysis of the present series (n = 20) and 31 patients from the literature identified 28 (55%) favourable responses to rHuEPO, including 16 CR and 12 PR. In the multivariate analysis, serum erythropoietin level <125 U/l was found to be associated with a favourable response to rHuEPO, whereas lack of transfusional support had borderline significance.
au Harmonic balance approach for a degenerate torus of a nonlinear jerk equation

The method of harmonic balance is used for the first time to find approximate expressions for the frequency and displacement amplitude of a degenerate torus arising in a third-order nonlinear oscillator, for a range of velocity amplitudes. The estimates compare favourably with numerically determined solutions. This development complements earlier works on the simpler situations of centres and limit cycles. ____________________________________________________________________ * Tel. : 61 7 37357556. E-mail address: H.Gottlieb@griffith.edu. au
The Isolation and Structural Determination of Flavonoids from Justicia Gendarussa

The current study was intended for isolation of bioactive polyphenolic compounds from methanol extract of Justicia Gendarussa and their subsequent characterization. The flavonoid compounds were isolated and identified by using thin layer chromatography (TLC), were qualified by using reverse phase high performance chromatography (RP-HPLC). Their structures and chemical bonds were analyzed using Ultraviolet-Visible spectrophotometer (UV-VIS spectrophotometer), Fourier Transform-Infra Red spectroscopy (FTIR), Nuclear magnetic resonance NMR (13C and 1H),LC-MS, DSC, SEM and EDX techniques. Two flavonoids were identified as Apigenin and Vitexin. For the first time Apigenin and Vitexin have been isolated successfully from the Justicia Gendarussa. The isolation of the above considered flavonoids would be helpful to practise plant-based pharmaceutical research to treat various difficulties linked with human diseases.
Marine Biodiversity : An Economic Valuation

A goods and services approach has been applied to determine the economic value of marine biodiversity in the UK. This paper presents the goods and services resulting from marine biodiversity in UK waters, detailing the habitats and species which provide them, and the likely impact of a decrease in biodiversity. Where possible a monetary value was assigned to each of the goods and services. Valuing the environment in monetary terms is still controversial, and the problems with this approach are recognised and discussed with particular reference to marine biodiversity. The monetary figures provided here are the best value estimates currently available, but they should only be used as indicators of value, and the strength of this monetary data lies in its capacity to raise awareness of the importance of marine biodiversity. A decline in UK marine biodiversity could result in a varying, and at present unpredictable, change in the provision of all these goods and services. This could result in severe impacts on society and the economy, including reduced resilience and resistance to change, declining marine environmental health and water quality, reduced fisheries potential, loss of recreational opportunities, decreased employment, and reduced carbon uptake.
Primary Trophoblast Cultures: Characterization of HLA Profiles and Immune Cell Interactions

Introduction Trophoblasts are essential in fetal-maternal interaction during pregnancy. The goal was to study HLA profiles of primary trophoblasts derived from placentas, and to investigate their usefulness in studying interaction with immune cells. Methods After enzymatic digestion of first-trimester placental tissue from seven donors (6-9 weeks gestation) and trophoblast enrichment we cultured cytotrophoblasts (CTB) in stem cell medium. CTB were differentiated into EVT in a Matrigel-containing medium. A subset of CTB/EVT was profiled for microRNA levels. Expression of classical HLA molecules and of HLA-G was studied by flow cytometry, qPCR, and ELISA. Secondary trophoblast cell lines JAR and JEG-3 were studied as controls. Lymphocytes were investigated during co-culturing with EVT. Results The trophoblasts could be easily maintained for several passages, upregulated classical trophoblast markers (GATA3, TFAP2C, chromosome-19 microRNAs), and upon differentiation to EVT they were selective in expressing HLA-C. EVT showed increasing expression of total HLA-G, an increasing proportion of HLA-G1 over G2- and G3 isoforms, and elevated excretion of soluble HLA-G. These features were distinct from those of the secondary trophoblast cell lines. TNF-α and IL-8 represented the most abundantly secreted cytokines by CTB, but their levels were minimal in EVT cultures. As proof of principle, we showed that EVT affect lymphocytes in three-day co-cultures (n=4) by decreasing activation marker HLA-DR. Conclusion We verified the possibility culturing trophoblasts from first-term placentas, and their capability of differentiating to HLA-G expressing EVT. This culture model better represents the in-vivo situation than previously studied secondary trophoblast cell lines and enables mechanistic studies of fetal-maternal interactions.
Feynman-diagram evaluation in the electroweak theory with computer algebra

The evaluation of quantum corrections in the theory of the electroweak and strong interactions via higher-order Feynman diagrams requires complicated and laborious calculations, which however can be structured in a strictly algorithmic way. These calculations are ideally suited for the application of computer algebra systems, and computer algebra has proven to be a very valuable tool in this field already over several decades. It is sketched how computer algebra is presently applied in evaluating the predictions of the electroweak theory with high precision, and some recent results obtained in this way are summarized.
Bit error rate (BER) performance enhancement technique of a wireless fading channel

Antenna diversity technique improves the instantaneous and average signal to noise ratio (SNR) by combining all the diversity branches. The channel noise and fading reduce the performance of any communication system through making loss of some information of the transmitted symbol. In this paper, we mathematically represented the effect of noise and multi-path fading on the transmitted signal. Then we performed a computer simulation study to show the BER performance of the fading channel and also showed how the BER performance of the fading channel could be improved by Antenna diversity technique.
Serotonin receptor 2C and mental disorders: Genetic, expression, and RNA editing studies

Serotonin receptor 2C (HTR2C) is one of the attractive candidate genes for studying pathophysiology of mental disorders. Here we overviewed the genetic, expression, and RNA editing studies suggesting the close relationship between HTR2C and major mental disorders including schizophrenia, bipolar disorder, and major depression. We especially focused on the human studies as well as with reference to relevant cellular and animal models. Possible significance of genetic variations affecting expression and RNA editing and appropriate animal models that mimic human mental disorders were discussed.