Miracle-dz/UniFAR-FTUs huggingface dataset:
Incorporation of [14C]glutamate into glutathione in rat brain

IT WAS reported by BERL, LAJTHA and WAELSCH (1961) that after administration of labelled glutamate the specific radioactivity of glutathione (GSH) in rat brain is relatively high: the specific radioactivity of GSH was similar to that of glutamate and considerably higher than that of other metabolites derived from glutamate (e.g. GABA), except glutamine. These observations implied that GSH is formed in a small and relatively active glutamate pool. Since the GSH is rapidly precipitated and fixed in the tissue by perfusing with silver nitrate, it appeared that this small glutamate pool might be located by using GSH as a histological marker in radioautographic experiments (GARFINKEL, 1962). With a view to determining the site of labelling of GSH in this way, a preliminary study was made of the labelling of GSH and other metabolites in the brain. ~L-[l-~~C]GIutarnate was selected as precursor in this study for the following reasons: (1) The 14C is removed as "CO, at the first step of the metabolism of ~-[ l -~~C]glutamate or a-~xo[l-~~C]glutarate. The 14C retained in the tissue is therefore present mainly in products in which the whole carbon skeleton is preserved (glutamine, GSH, glutamate-containing polypeptides and protein). (2) The amount of ~-[ l -~~C]glutamate which enters the brain can be estimated approximately by determining the radioactivity of ~-[ l -~~Clglutamate in the tissue, since the uptake of D-glutamate by brain tissue in vitro is similar to that of the natural isomer (TAKAGAKI, HIRANO and NAGATA, 1959). In contrast to the natural isomer, D-glutamate is metabolically relatively inert (TAKAGAKI et al., 1959; LEVI and LAITHA, 1965). It can be expected, therefore, that within a short experimental period ~-[ l -~~C]glutamate will not be metabolized appreciably, except by conversion to ~-[l-*'c]glutamine (LEVINTOW and MEISTER, 1953). ~ [ l ~ ~ C ] G h ~ t a m i n e can be distinguished from the L isomer by using a CI. welchii preparation which will decarboxylate only the L form (LEVINTOW and MEISTER, 1953).
Role of the Sp Family of Transcription Factors in the Ontogeny of Growth Hormone Receptor Gene Expression*

The growth hormone (GH) receptor is essential for the actions of growth hormone on postnatal growth and metabolism. GH receptor transcripts are characterized by the presence of disparate 5′-untranslated exons. Factors regulating the expression of the GC rich L2 transcript of the murine GH receptor gene have hitherto remained unidentified. To characterize the mechanisms regulating expression of the L2 transcript, primer extension and ribonuclease protection assays were used to identify transcription start sites in RNA from liver of adult mice. Transient transfection experiments revealed that 2.0 kilobase pairs of the L2 5′-flanking sequence exhibited promoter activity in BNL CL.2 (mouse liver) cells, CV-1 (monkey kidney) cells, and HRP.1 trophoblasts. Deletional analysis localized a major regulatory region to within 75 base pairs of the 5′ transcription start site. Sequence analysis revealed that the region contained consensus binding sites for the Sp family of transcription factors. Standard gel shift and supershift analysis using liver nuclear extracts established that Sp1 and Sp3 bound this regulatory element. Transfection of wild type but not mutant decoy oligonucleotides into BNL CL.2 cells decreased the activity of the L2 promoter. Overexpression of Sp1 and Sp3 protein in Drosophila Schneider cells established that Sp3 is more potent than Sp1 in transactivating the L2 promoter. Co-transfection experiments further established that Sp1 antagonizes the activity of Sp3 to transactivate the L2 promoter. Western blot analysis of liver nuclear extracts revealed that the levels of Sp3 increase significantly after birth, suggesting a role for the Sp family of transcription factors in controlling the fetal to postnatal increase in GH receptor gene expression.
A SIMPLE EXPLANATION.

Skin, the largest organ of the body, and is 16% of total body weight, has three main functions; protective, sensory and thermoregulatory. The last two functions are controlled by thalamus and hypothalamus. Under the skin is a subcutaneous connective tissue comprised of collagen, the largest protein type in the body. Collagen has both a piezoelectric (responds to change in pressure) and a pyroelectric (responds to changes in temperature) component.
Phase I and pharmacokinetic study of vorinostat (suberoylanilide hydroxamic acid) in Japanese patients with solid tumors

Vorinostat (suberoylanilide hydroxamic acid), a potent, oral histone deacetylase inhibitor, has demonstrated clinical activity in non‐Japanese patients with various hematological and solid tumors. We sought to determine the maximum tolerated dose and a recommended phase II dose for 18 Japanese patients with solid tumors (median age, 58 years; range, 25–72 years) who failed standard therapy. Patients received vorinostat for 14 days followed by a 7‐day rest. The initial dose was 100 mg twice daily escalating by 100 mg twice daily. Once‐daily dosing was tested at 400 and 500 mg. A maximum tolerated dose could not be identified. Dose‐limiting toxicities (thrombocytopenia, anorexia, and fatigue) were observed in two of six patients receiving 200 mg twice daily and in one of six patients receiving 500 mg once daily. In the 100–500 mg dose range, vorinostat area under the concentration–time curve increased in proportion to dose with a pharmacokinetic profile similar to that established in non‐Japanese patients. Vorinostat doses of 200 mg twice daily or 500 mg once daily for 14 days followed by a 7‐day rest were well tolerated and are candidate doses for phase II trials, although a maximum tolerated dose for vorinostat was not reached. (Cancer Sci 2009; 100: 1728–1734)
Dynamic reorientation of cultured cells and stress fibers under mechanical stress from periodic stretching.

Cell lines derived from rat aorta and frog kidney were cultured on elastic membrane, and mechanical stress was given to the cells by stretching the membrane periodically. Cell reorientation oblique to the direction of stretching occurred as a result of the rapid withdrawal of cell periphery located along the direction of stretching and gradual extension of the cell membrane toward the direction oblique to the direction of stretching. Dynamic reorganization of stress fibers in living cells was visualized by labeling stress fibers with TRITC(3)-actin or EGFP-tagged moesin fragments with actin-binding ability. Stress fibers aligned in the direction of stretching disappeared soon after the start of stretching and then obliquely reoriented stress fibers appeared. The stretch-induced reorientation of cultured cells was suppressed by an inhibitor of stretch-activated (SA) cation channels and by a Ca(2+) chelator. However, the rearrangement of stress fibers was not affected by these agents. From these results, we suggest that Ca(2+) influx via SA channels is involved in stretch-induced cell reorientation but stress fiber rearrangement is independent of SA channels. Therefore, cell reorientation does not simply depend on the arrangement of stress fibers but may be controlled by some additional mechanism(s) which is regulated by calcium signaling.
ismantling Mandates in he Treatment of Heart Failure * arl

he Studies Of Left Ventricular Dysfunction (SOLVD) rial is a landmark study in the management of heart failure. he treatment limb of this trial (1) demonstrated unequivcally that long-term administration of the angiotensinonverting enzyme (ACE) inhibitor enalapril reduced morality and hospitalization in patients with New York Heart ssociation functional class II and III heart failure on tandard background therapy and thus, greatly extended the opulation base for proven ACE inhibitor benefit beyond hat of the severe functional class IV patients studied in the ooperative North Scandinavian Enalapril Survival Study CONSENSUS) trial (2). The prevention limb of the OLVD trial then also demonstrated ACE inhibitor benfit in patients with left ventricular (LV) systolic dysfunction ith minimal to no symptoms (3).
Dimensionality reduction for voice disorders identification system based on Mel Frequency Cepstral Coefficients and Support Vector Machine

Nowadays, due to the severe daily activities and vocal abuse, many diseases affect the mechanism of voice production which causes pathological voices. Therefore, the identification of voice diseases becomes a real challenge. In this context, the automatic speech recognition can provide great results as a complementary tool to other medical techniques. This paper proposes a reliable algorithm based on short-term cepstral parameters, Linear Discriminant Analysis (LDA) as dimensionality reduction method and Support Vector Machine (SVM) as classifier. A full comparative study is established and the system performance is evaluated in terms of accuracy, sensitivity, specificity, precision and Area Under Curve (AUC). Our findings demonstrate that the detection of voice disorders can be efficient using only the original Mel Frequency Cepstral Coefficients (MFCC) ignoring their first and second derivative.
Antisense therapeutics for neurofibromatosis type 1 caused by deep intronic mutations

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting 1:3,500 individuals. Disease expression is highly variable and complications are diverse. However, currently there is no specific treatment for the disease. NF1 is caused by mutations in the NF1 gene, approximately 2.1% of constitutional mutations identified in our population are deep intronic mutations producing the insertion of a cryptic exon into the mature mRNA. We used antisense morpholino oligomers (AMOs) to restore normal splicing in primary fibroblast and lymphocyte cell lines derived from six NF1 patients bearing three deep intronic mutations in the NF1 gene (c.288+2025T>G, c.5749+332A>G, and c.7908‐321C>G). AMOs were designed to target the newly created 5′ splice sites to prevent the incorporation of cryptic exons. Our results demonstrate that AMO treatment effectively restored normal NF1 splicing at the mRNA level for the three mutations studied in the different cell lines analyzed. We also found that AMOs had a rapid effect that lasted for several days, acting in a sequence‐specific manner and interfering with the splicing mechanism. Finally, to test whether the correction of aberrant NF1 splicing also restored neurofibromin function to wild‐type levels, we measured the amount of Ras‐GTP after AMO treatment in primary fibroblasts. The results clearly show an AMO‐dependent decrease in Ras‐GTP levels, which is consistent with the restoration of neurofibromin function. To our knowledge this is the first time that an antisense technique has been usedsuccessfully to correct NF1 mutations opening the possibility of a therapeutic strategy for this type of mutation not only for NF1 but for other genetic disorders. Hum Mutat 30, 454–462, 2009. © 2009 Wiley‐Liss, Inc.
Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect.

BACKGROUND In the absence of clinical folate deficiency, periconceptional supplementation with folic acid reduces a woman's risk of having an infant with a neural-tube defect. Since antiserum to folate receptors induces embryo resorption and malformations in rats, we hypothesized that autoantibodies against folate receptors in women may be associated with pregnancy complicated by a neural-tube defect. METHODS Serum from 12 women who were or had been pregnant with a fetus with a neural-tube defect and from 24 control women (20 with current or prior normal pregnancies and 4 who were nulligravid) was analyzed for autoantibodies by incubation with human placental folate receptors radiolabeled with [3H]folic acid. The properties of these autoantibodies were characterized by incubating serum and the autoantibodies isolated from serum with placental membranes, ED27 cells, and KB cells, which express the folate receptors. RESULTS Serum from 9 of 12 women with a current or previous affected pregnancy (index subjects) and 2 of 20 control subjects contained autoantibodies against folate receptors (P<0.001). The autoantibodies blocked the binding of [3H]folic acid to folate receptors on placental membranes and on ED27 and KB cells incubated at 4 degrees C and blocked the uptake of [3H]folic acid by KB cells when incubated at 37 degrees C. CONCLUSIONS Serum from women with a pregnancy complicated by a neural-tube defect contains autoantibodies that bind to folate receptors and can block the cellular uptake of folate. Further study is warranted to assess whether the observed association between maternal autoantibodies against folate receptors and neural-tube defects reflects a causal relation.
Can mortality rates for patients who die within the emergency department, within 30 days of discharge from the emergency department, or within 30 days of admission from the emergency department be easily measured?

Objectives: Death rates are an outcome that can be used to describe a service. We measured three death rates that can be used to describe an emergency department (ED): death rates for those seen in the ED and discharged, those that die within the ED, and those that die after admission. We also wanted to establish how easy it was to obtain these rates and how frequently autopsy was performed. Setting: ED within a large teaching hospital. Results: Between 1 December 2003 and 1 December 2004, 76 060 patients attended the ED of which 205 died within the department. A total of 16 489 were admitted of which 876 died within 30 days. A total of 59 366 were discharged home of which 111 subsequently died over the next 30 days. The rates were 0.19% (111/59 366) for those discharged, 4.6% (766/16 489) for those admitted, and 0.27% (205/76 060) for those patients attending the ED who died within it. The autopsy rate was low (20%) and was more likely if the patient died in the department, died within the first few days of admission, or was young. The data were easy to collect. Conclusions: These three death rates were easy to calculate and could be used to describe the outcome of an ED service. Further research to establish the range of rates for different departments is now required to determine their potential use.
Size at birth, adult intestinal calcium absorption and 1,25(OH)(2) vitamin D.

BACKGROUND Adult bone mineral status is modified by early environmental influences, but the mechanism of this phenomenon is unknown. Intestinal calcium absorption and vitamin D metabolism are integrally involved in bone metabolism and may be programmed during early life. AIM To examine the early-life influences on calcium absorption and its control in 322 post-menopausal female twins. METHODS Intestinal calcium absorption was assessed by the stable strontium (Sr) method. Serum PTH, 25(OH) and 1,25(OH)(2) vitamin D were measured and recalled birth weight recorded. RESULTS Fractional intestinal Sr absorption (alpha Sr) was correlated with serum 1,25(OH)(2) vitamin D (p<0.001), but not with 25(OH) vitamin D. Birth weight was inversely associated with serum 1,25(OH)(2) vitamin D (p=0.04), the association being independent of serum calcium, phosphate, creatinine and PTH. Birth weight was inversely correlated with alpha Sr (p=0.03), this association being independent of age, season, customary calcium intake and serum 25(OH) vitamin D; however, when serum 1,25(OH)(2) vitamin D was added into the model, the association became non-significant, suggesting that the association was partially mediated via serum 1,25(OH)(2) vitamin D. DISCUSSION We found a significant inverse association between birth weight and intestinal calcium absorption that is partially explained by an association between serum 1,25(OH)(2) vitamin D and birth weight. This suggests a mechanism whereby the intra-uterine environment might affect adult skeletal status.
Evidence for adaptive phenotypic differentiation in Baltic Sea sticklebacks

The evidence for adaptive phenotypic differentiation in mobile marine species remains scarce, partly due to the difficulty of obtaining quantitative genetic data to demonstrate the genetic basis of the observed phenotypic differentiation. Using a combination of phenotypic and molecular genetic approaches, we elucidated the relative roles of natural selection and genetic drift in explaining lateral plate number differentiation in threespine sticklebacks (Gasterosteus aculeatus) across the entire Baltic Sea basin (approximately 392 000 km2). We found that phenotypic differentiation (PST = 0.213) in plate number exceeded that in neutral markers (FST = 0.008), suggesting an adaptive basis for the observed differentiation. Because a close correspondence was found between plate phenotype and genotype at a quantitative trait loci (QTL; STN381) tightly linked to the gene (Ectodysplasin) underlying plate variation, the evidence for adaptive differentiation was confirmed by comparison of FST at the QTL (FSTQ = 0.089) with FST at neutral marker loci. Hence, the results provide a comprehensive demonstration of adaptive phenotypic differentiation in a high‐gene‐flow marine environment with direct, rather than inferred, verification for the genetic basis of this differentiation. In general, the results illustrate the utility of PST–FST–FSTQ comparisons in uncovering footprints of natural selection and evolution and add to the growing evidence for adaptive genetic differentiation in high‐gene‐flow marine environments, including that of the relatively young Baltic Sea.
Understanding water deficit stress-induced changes in the basic metabolism of higher plants – biotechnologically and sustainably improving agriculture and the ecoenvironment in arid regions of the globe

Water is vital for plant growth, development and productivity. Permanent or temporary water deficit stress limits the growth and distribution of natural and artificial vegetation and the performance of cultivated plants (crops) more than any other environmental factor. Productive and sustainable agriculture necessitates growing plants (crops) in arid and semiarid regions with less input of precious resources such as fresh water. For a better understanding and rapid improvement of soil–water stress tolerance in these regions, especially in the water-wind eroded crossing region, it is very important to link physiological and biochemical studies to molecular work in genetically tractable model plants and important native plants, and further extending them to practical ecological restoration and efficient crop production. Although basic studies and practices aimed at improving soil water stress resistance and plant water use efficiency have been carried out for many years, the mechanisms involved at different scales are still not clear. Further understanding and manipulating soil–plant water relationships and soil–water stress tolerance at the scales of ecology, physiology and molecular biology can significantly improve plant productivity and environmental quality. Currently, post-genomics and metabolomics are very important in exploring anti-drought gene resources in various life forms, but modern agriculturally sustainable development must be combined with plant physiological measures in the field, on the basis of which post-genomics and metabolomics have further practical prospects. In this review, we discuss physiological and molecular insights and effects in basic plant metabolism, drought tolerance strategies under drought conditions in higher plants for sustainable agriculture and ecoenvironments in arid and semiarid areas of the world. We conclude that biological measures are the bases for the solutions to the issues relating to the different types of sustainable development.
No association of Borna disease virus with psychiatric disorders among patients in Northern Kyushu, Japan

There is controversy over the prevalence of Borna disease virus (BDV) antibodies and its RNA in the peripheral blood mononuclear cells (PBMCs) of psychiatric patients, and the contribution of BDV to human psychiatric disorders. We examined 299 plasma and 229 PBMC samples. No plasma samples were positive for BDV‐p40, p24 or gp18 antibodies by western blot analysis. The prevalence of BDV RNA in the psychiatric (schizophrenic) patients (1.8%) was not significantly different from that in the healthy volunteers (0.6%). The nucleotide sequences of BDV p40 and p24 were highly conserved with those of BDV He/80. Our results suggested that there is a lack of association between BDV infection and psychiatric disorders among the patients in Northern Kyushu, Japan. J. Med. Virol. 61:336–340, 2000. © 2000 Wiley‐Liss, Inc.
Up-to-date report of botulinum toxin therapy in patients with drooling caused by different etiologies.

PURPOSE In this study, we evaluated the clinical data for patients with drooling caused by various diseases, treated by injection of botulinum toxin A. We also present a controlled follow-up study documenting efficiency, possible adverse events, and duration of the effect of treatment. PATIENTS AND METHODS Thirteen patients with drooling caused by head and neck carcinoma, neurodegenerative diseases, or stroke received injections of 50 to 65 U botulinum toxin A (Botox; Allergan, Irvine, CA) in both submandibular and both parotid glands under sonographic control. We measured whole salivary flow rate and the salivary analytes of total protein, alpha-amylase, acid phosphatase, kallikrein, and immunoglobulin A at various times before and after injection. The patients were examined for severity of symptoms, including sonographic investigation of cephalic salivary glands. RESULTS All 13 patients reported a distinct improvement of their symptoms within 2 weeks after toxin injection. Three patients noted a return of high salivation rates after 12 weeks. Duration of toxin effect varied widely between individuals. In general, salivary flow rates dropped sharply within 1 week after injection but had risen again after 12 weeks. Conversely, analyte concentrations increased in the first stages of treatment and later decreased, returning to pretherapy levels. Sonography did not reveal any major changes of salivary gland parenchyma, and side effects were absent. CONCLUSIONS Local injection of botulinum toxin A into the salivary glands proved to be a dependable therapy for drooling caused by various etiologies, as shown in 13 patients. Adverse events were not seen. The effect of toxin application lasted for about 3 months. To further clarify this aspect, long-term studies are under way.
Modulation of androgen and estrogen receptor expression by antiepileptic drugs and steroids in hippocampus of patients with temporal lobe epilepsy

Purpose: Many of the antiepileptic drugs (AED) used in therapy of temporal lobe epilepsy (TLE) are known as cytochrome P450 (CYP, P450) inducers. These AEDs are thought to modulate androgen and estrogen pathways in hippocampus, and therefore cause mental and reproductive disorders found in TLE patients. In the present study, we analyzed expression of androgen receptor (AR), estrogen receptor α (ERα), and CYP3A in the hippocampus of TLE patients and in murine hippocampal cell line HN25.1.
Change in Speed and Direction of the Jet near the Core in the Quasar 3C 279

Intensive monitoring of the innermost jet in the quasar 3C 279 at 43 GHz from 1998 March to 2001 April with the Very Long Baseline Array, in combination with previous observations, reveal (1) an increase in apparent speed from 5c to 17c and (2) a change in projected direction of the jet by ∼20°. These effects could result from a small increase in the intrinsic viewing angle of the jet nozzle from Θ ≲ 0. °5 to Θ ≲ 1. °6, with no increase required in the actual speed of the flow, which corresponds to a Lorentz factor γ ≳ 20. The Lorentz factor ∼20 and viewing angle ∼0. °5 imply that the Doppler factor is at least 39 close to the core; this extreme value explains the high flux density and rapid variability of 3C 279 across the electromagnetic spectrum.