Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of ciprofloxacin on eucaryotic pyrimidine nucleotide biosynthesis and cell growth

Several of the new 4-quinolones significantly increase the incorporation of [3H]thymidine into the DNA of mitogen-stimulated human lymphocytes. This study suggests that ciprofloxacin inhibits de novo pyrimidine biosynthesis, thereby resulting in a compensatory increase in the uptake of pyrimidine precursors through salvage pathways, and that additional effects may affect eucaryotic cell growth. Incorporation of deoxyuridine, uridine, and orotic acid as well as thymidine was increased in the presence of ciprofloxacin, one of the antibacterially most active of the new 4-quinolones. In contrast, the uptake was decreased in very high concentrations of the drug. Culture in HAT (hypoxanthine, aminopterine, thymidine) medium, which blocks de novo thymidylate synthesis, abrogated the increase in [3H]thymidine incorporation induced by ciprofloxacin. Ciprofloxacin also failed to increase the uptake of [14C]hypoxanthine or leucine, indicating a selective effect on pyrimidine and not on purine nucleotide biosynthesis. N-(Phosphonacetyl)-L-aspartate, an inhibitor of pyrimidine nucleotide biosynthesis, also increased [3H]thymidine incorporation in phytohemagglutinin-stimulated lymphocytes in a fashion similar to ciprofloxacin. The growth of several cell lines was partially inhibited by ciprofloxacin at 20 micrograms/ml and completely inhibited at 80 to 160 micrograms/ml. Growth inhibition by ciprofloxacin could not be restored by the addition of uridine to the medium. Chromosome breaks, gene amplification, or other genetic alterations could not be detected in human lymphocytes incubated with up to 25 micrograms of ciprofloxacin per ml.
Dystrophic Calcification in Chronic Leg Ulcers—A Clinicopathologic Study

BACKGROUND Dystrophic calcification (DC) is a risk factor for conservative treatment failure in chronic leg ulcers of various pathologies. PATIENTS AND METHODS We performed a retrospective noncontrolled trial of 212 patients with 362 chronic leg ulcers who underwent ulcer shave excision with subsequent skin grafting. The ulcers existed for at least 3 months, and no healing was achieved with good ulcer care. Tissue was subjected to histopathology (hematoxylin‐eosin and van Kossa stains). RESULTS DC was evident in 39 patients (18%). Metaplastic subcutaneous bone formation was observed in 15 patients (7%). Clinical symptoms associated with DC were resistance to good ulcer care, pain, and ineffective effects of compression therapy (in venous ulcers). Ulcers were treated with deep dermatome shaving of the ulcer bed and surgical removal of DC. In the same setting, defects were closed using mesh graft transplantation. The procedure achieved a complete take rate in 80% and a significant decrease of pain in 95% of cases. When comparing the take rates in patients with and without DC, DC had a negative effect on outcome (take rate: 91% without DC vs 80% with DC, p<.05). CONCLUSIONS DC is resistant to conservative treatment. The first‐line treatment is deep ulcer dermatome shaving and complete removal of calcifications whenever possible. The authors have indicated no significant interest with commercial supporters.
Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and vascular remodeling.

RATIONALE Our previous studies found that Na(+)/H(+) exchanger (NHE) activity played an essential role in pulmonary artery smooth muscle cell (PASMC) proliferation and in the development of hypoxia-induced pulmonary hypertension and vascular remodeling. Other investigators recently observed increased expression of the NHE isoform 1 (NHE1) gene in rodents with pulmonary hypertension induced by hypoxia. However, a causal role for the NHE1 gene in pulmonary hypertension has not been determined. OBJECTIVES To determine the causal role of the NHE1 gene in pulmonary hypertension and vascular remodeling. METHODS We used NHE1-null mice to define the role of the NHE1 gene in the development of pulmonary hypertension and remodeling induced by hypoxia and to delineate the NHE1 regulatory pathway. MEASUREMENTS AND MAIN RESULTS After 2 weeks of exposure to hypoxia, in contrast to wild-type hypoxic littermates, there was no significant increase in right ventricular systolic pressure, in the ratio of right ventricular to left ventricular plus septal weight [RV/(LV + S)], or in medial wall thickness of the pulmonary arterioles in homozygous mice (NHE1(-/-)). There was a significant decrease in Rho kinase (ROCK1 and ROCK2) expression, accompanied by an increase in p27 expression in NHE1(-/-) mice. CONCLUSIONS Our study demonstrated that deficiency of the NHE1 gene prevented the development of hypoxia-induced pulmonary hypertension and vascular remodeling in mice and revealed a novel regulatory pathway associated with NHE1 signaling.
Destabilization of mayonnaise induced by lipid crystallization upon freezing

The thermal and rheological history of mayonnaise during freezing and its dispersion stability after the freeze-thaw process were investigated. Mayonnaise was cooled to freeze and stored at −20 to −40 °C while monitoring the temperature; penetration tests were conducted on the mayonnaise, which was sampled at selected times during isothermal storage at −20 °C. Significant increases in the temperature and stress values due to water-phase crystallization and subsequent oil-phase crystallization were observed. The water phase crystallized during the cooling step in all the tested mayonnaise samples. The oil phases of the prepared mayonnaise (with rapeseed oil) and commercial mayonnaise crystallized during isothermal storage after 6 and 4 h, respectively, at −20 °C. The dispersion stability was evaluated from the separation ratio, which was defined as the weight ratio of separated oil after centrifuging to the total amount of oil in the commercial mayonnaise. The separation ratio rapidly increased after 4 h of freezing. This result suggests that crystallization of the oil phase is strongly related to the dispersion stability of mayonnaise. Graphical abstract Temperature changes during storage at −20 °C and separation ratio, X, after the freeze-thaw process of commercially available mayonnaise.
Evidence that a non‐RGD domain in rat osteopontin is involved in cell attachment

The bone sialoprotein osteopontin (OPN) promotes cell attachment and spreading through its RGD (Arg‐Gly‐Asp) sequence. To study additional regions of OPN involved in cell attachment, peptides of rat OPN were evaluated for their capacity to mediate cell binding to wells in vitro. Human gingival fibroblasts were incubated on microtiter plates coated with either OPN or OPN peptides. A peptide of Mr 28 kD, obtained after digestion with endoproteinase Arg‐C and isolated by reversed‐phase HPLC, enhanced cell attachment to a similar degree as OPN. Sequence analysis showed that the amino terminus of the 28 kD peptide starts at Ser142 and therefore does not contain the RGD cell attachment sequence (residues 128–130). Cell attachment mediated through both OPN and the 28 kD peptide was blocked by the addition of GRGDSPA peptides or LM‐609, a monoclonal antibody to the integrin αVβ3, a receptor for vitronectin. A variant peptide, GRG‐ESPA, did not alter cell attachment. Based on these observations, we conclude that (1) binding of OPN and the 28 kD peptide to fibroblasts involves binding to αVβ3, (2) a site other than the RGD sequence on OPN is also involved in binding to integrins, and (3) the binding of this second site to αVβ3 is inhibited by RGD‐containing peptides.
Oncogene proteins and proliferation antigens in thymomas: increased expression of epidermal growth factor receptor and Ki67 antigen.

AIMS--To examine thymomas for proteins encoded by oncogenes and to determine whether their presence correlates with tumour growth and associated myasthenia gravis. METHODS--Sections of 24 thymomas were incubated with anti-EGF receptor (EGF-R), anti-Ki67 antigen, anti-p53, and anti-bcl-2 antibodies, and then stained using the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. Cell suspensions and epithelial cell cultures from some of the tumours were also studied. RESULTS--Whereas EGF-R expression was not detected in any of the controls (but only in a 20 week old fetus), it was detected in neoplastic epithelial cells of all thymomas, and was most strongly expressed in metastases and in samples from donors with severe myasthenia gravis. Ki67 labelling was also increased, especially in the larger thymomas. Epithelial expression of both of these markers was confirmed in fresh cell suspensions and monolayer cultures from the five available cases. In contrast, p53 and bcl-2 were not detected in the neoplastic cells, but bcl-2 was present in the intermingling thymocytes. CONCLUSIONS--Neoplastic thymoma cells express EGF-R and Ki67, but there is no concomitant increase in the expression of p53 and bcl-2 proteins. Increased EGF-R expression may result in increased proliferation of neoplastic cells and also in myasthenia gravis. Measurement of EGF-R concentrations may be of prognostic value. The bcl-2 staining pattern in T lymphocytes illustrates the broad spectrum of maturational stages in thymoma lymphocytes.
CBL1, a Calcium Sensor That Differentially Regulates Salt, Drought, and Cold Responses in Arabidopsis Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.012393.

Although calcium is a critical component in the signal transduction pathways that lead to stress gene expression in higher plants, little is known about the molecular mechanism underlying calcium function. It is believed that cellular calcium changes are perceived by sensor molecules, including calcium binding proteins. The calcineurin B–like (CBL) protein family represents a unique group of calcium sensors in plants. A member of the family, CBL1, is highly inducible by multiple stress signals, implicating CBL1 in stress response pathways. When the CBL1 protein level was increased in transgenic Arabidopsis plants, it altered the stress response pathways in these plants. Although drought-induced gene expression was enhanced, gene induction by cold was inhibited. In addition, CBL1-overexpressing plants showed enhanced tolerance to salt and drought but reduced tolerance to freezing. By contrast, cbl1 null mutant plants showed enhanced cold induction and reduced drought induction of stress genes. The mutant plants displayed less tolerance to salt and drought but enhanced tolerance to freezing. These studies suggest that CBL1 functions as a positive regulator of salt and drought responses and a negative regulator of cold response in plants.
Effects of neonatal enucleation on the organization of callosal linkages in striate cortex of the rat

Lewis and Olavarria ([1995] J. Comp. Neurol. 361:119–137) showed that the mediolateral organization of callosal linkages differs markedly between medial and lateral regions of striate cortex in the rat. Thus, callosal fibers originating from medial regions of striate cortex interconnect loci that are mirror‐symmetric with respect to the midsagittal plane. In contrast, fibers from lateral regions of striate cortex show a reversed pattern of connections: tracer injections into the 17/18a border produce retrograde cell labeling in regions medial to the contralateral 17/18a border, whereas injections placed somewhat medial to the 17/18a border label cells located at the contralateral 17/18a border.
SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix

Secreted protein, acidic and rich in cysteine (SPARC), is a multifunctional matricellular glycoprotein. In vitro, SPARC has antiangiogenic properties, including the ability to inhibit the proliferation and migration of endothelial cells stimulated by bFGF and VEGF. Previously, we demonstrated that platelet‐derived SPARC also inhibits angiogenesis and impairs the growth of neuroblastoma tumors in vivo. In the present study, we produced rhSPARC in the transformed human embryonic kidney cell line 293 and show that the recombinant molecule retains its ability to inhibit angiogenesis. Although 293 cell proliferation was not affected by exogenous expression of SPARC in vitro, growth of tumors formed by SPARC‐transfected 293 cells was significantly impaired compared to tumors comprised of wild‐type cells or 293 cells transfected with a control vector. Consistent with its function as an angiogenesis inhibitor, significantly fewer blood vessels were seen in SPARC‐transfected 293 tumors compared to controls, and these tumors contained increased numbers of apoptotic cells. Light microscopy revealed small nests of tumor cells surrounded by abundant stromal tissue in xenografts with SPARC expression, whereas control tumors were comprised largely of neoplastic cells with scant stroma. Mature, covalently cross‐linked collagen was detected in SPARC‐transfected 293 xenografts but not in control tumors. Our studies suggest that SPARC may regulate tumor growth by inhibiting angiogenesis, inducing tumor cell apoptosis and mediating changes in the deposition and organization of the tumor microenvironment. © 2005 Wiley‐Liss, Inc.
“One Hour He Is a Christian and the Next He Is a Muslim!” A Family Dispute from the Cairo Geniza

ABSTRACT This study publishes a newly identified letter to Moses Maimonides reconstructed from three Geniza fragments. The letter describes an inheritance dispute over real estate in the Egyptian delta town of al-Maḥalla. Having a letter written by a litigant provides information on what took place outside of court, information that is often missing from legal records. This allows us to explore the dynamics of a dispute in which one side makes a legal move, and the other counters with a move outside of court, and vice versa. These manoeuvrings included action in Jewish and Muslim courts, appeal to a jurisconsult, social pressure and performative disregard to the boundaries of the religious communities. As a result, we can conceive of the legal arena not only as encompassing different legal institutions but also as a social space constituted by the ways litigants experienced and interacted with legal institutions.
Small size of food particles and age as risk factors for gastric dilatation volvulus in great danes

A case-control study was conducted to investigate whether age, gender, neuter status, type of food, feeding frequency, food intake time, interval between feeding and exercise, duration of exercise and overall physical activity were risk factors for gastric dilatation volvulus (GDV) in the great dane. The sample population consisted of 38 great danes with acute GDV (cases) and 71 great danes owned by members of the Dutch Great Dane Association (controls). Information on the risk factors was collected by using clinical data in combination with a questionnaire, and the data were analysed by backward stepwise conditional logistic regression analysis. Dogs fed a diet containing particles of food >30 mm in size (kibble and/or dinner and/or home-prepared food with large pieces of meat) had a lower risk of GDV than dogs fed a diet containing only particles <30 mm in size (kibble or dinner and/or canned meat and/or home-prepared food cut into small pieces or ground in a food processor). Increasing age was also a risk factor for GDV. Gender, neuter status, feeding frequency, food intake time, the interval between feeding and exercise, the duration of exercise, and overall physical activity were not identified as risk factors. Feeding a diet including large pieces of meat may help to reduce the incidence of GDV in great danes.
Increase in Circulating Insulin Induced by Atrial Natriuretic Peptide in Normal Humans

To search for possible metabolic interactions of α-human-atrial natriuretic peptide (αhANP), we evaluated in 20 normal subjects blood levels of αhANP, glucose, insulin, cortisol, electrolytes, catecholamines, free fatty acids, carnitine and amino acids, blood pressure (BP), and heart rate before, during, and after a 45-min infusion of synthetic αhANP. Group A [n = 10] was studied on liberal and Group B on three consecutive sodium (Na) intakes of 17, 140, and 310 mM/day. Plasma αhANP was slightly but not significantly higher following 5 days on “normal” or high than on low Na+ intakes. ahANP infused at 0.1 μg/kg/min produced on all Na+ intakes comparable percentage increases in plasma insulin (+ 34 to 63%, p < 0.001), norepinephrine (+ 76 to 155%, p < 0.001) and heart rate (p < 0.001), and a similar fall in diastolic BP (p < 0.001). Plasma glucose tended to be decreased slightly and cortisol was reduced; epinephrine, dopamine, and potassium levels were not significantly modified. As evaluated in group A, serum free fatty acids were increased (p < 0.01), plasma free carnitine levels were reduced (p < 0.001), and amino acids were not consistently altered. These findings indicate that in normal humans ahANP may, on various sodium intakes, modulate insulin secretion and/or metabolism and elicit a possibly baroreflex-mediated sympathetic activation and lipolysis.
Effects of anoxia on megakaryocyte progenitors derived from cord blood CD34pos cells

Abstract: Background: Severe hypoxic insults to the fetus and neonate are associated with the development of thrombocytopenia. The thrombocytopenia in some cases is the result of disseminated intravascular coagulation, but that mechanism fails to account for all, perhaps the majority, of cases.
Association between obesity and asthma in 4-11 year old children in the UK.

BACKGROUND There is evidence of a positive association between asthma and obesity in adults and in children. We investigated, in a large sample of English and Scottish primary school children, whether there is a consistent association between fatness and asthma symptoms in Britain. METHODS A cross sectional analysis was made of 18 218 children aged 4-11 years who participated in the 1993 or 1994 surveys of the National Study of Health and Growth (NSHG). Children belonged either to English or Scottish representative samples, or an English inner city sample. Asthma attacks in the previous year, occasional wheeze, or persistent wheeze were the symptoms used in the analysis. Body mass index (BMI) and the sum of triceps and subscapular skinfolds converted to standard deviation scores (SDS) were used to assess levels of fatness. RESULTS A total of 14 908 children (81.8%) were included in the analysis. In the multiple logistic analysis BMI and asthma (asthma attacks or wheeze) were associated in the representative sample (OR for the comparison of the 10th and 90th centiles of BMI 1.28, 95% CI 1.11 to 1.48), but sum of skinfolds was unrelated to asthma symptoms in most analyses. The association between asthma and BMI was stronger in girls than in boys in the inner city sample, but less convincingly in the representative sample. CONCLUSIONS Levels of obesity are associated with asthma symptoms regardless of ethnicity. The association is more consistent for BMI than for sum of skinfolds, partly because obese children are more advanced in their maturation than other children. There is some evidence that, as in adults, the association is stronger in girls than in boys, but only in the multiethnic inner city sample.
Automatic 3-D Building Factor Analyses of a Grain-Oriented Model Transformer Core

The literature reports various transformer model core studies on local values of the building factor (BF), which consider the core as a 2-D single-package object. For the first time, we report 3-D BF analyses of a three-phase core that exhibits three different widths of packages. The inner BF values were determined by taking advantage of 25 channels of 2.5 mm width through the entire core. BF profiles along the channels were measured by means of a thermistor sensor that was controlled by a 3-D scanning system. For a nominal induction of 1.7 T, the results indicate that the main package of maximum width and thickness behaves similarly to one-package cores, with minimum BF in outer limbs and maximum BF (however, of reduced intensity) in the T joint. On the other hand, outer packages of reduced width and thickness show distinctly reduced BF, especially in the T joints. The results indicate that 2-D studies are not representative of peripheral packages. They show specific performance, especially due to the usual combination of circular limbs with semicircular yokes. The resulting regional off-plane z -flux seems to have a balancing function which reduces the effects of overlaps. However, low BF in the peripheral packages does not indicate good performance. Rather, it indicates poor exploitation of the core material.
Effect of Feeding Status on Mortality Response of Adult Bed Bugs (Hemiptera: Cimicidae) to Some Insecticide Products

ABSTRACT Fresh and aged residual deposits of several insecticide products were tested against bed bug adults to determine if a recent bloodmeal affected their mortality response to the residues. The bed bugs with a recent bloodmeal survived significantly longer compared with the unfed ones on their exposure to fresh or aged residual deposits of chlorfenapyr and aged residual deposits of deltamethrin on a wooden substrate. Even though the survival time of fed bed bugs was significantly longer than that of unfed ones on their exposure to fresh residue of deltamethrin and aged residue of desiccant pyrethrin dust, these treatments resulted in similarly high final mortalities regardless of feeding status of the insects. Mortality responses of fed and unfed bed bugs were similar to fresh or aged residual deposits of imidacloprid + cyfluthrin combination and fresh residual deposits of desiccant pyrethrin dust. Topical application assays indicated that a recent bloodmeal significantly increased the bed bug’s survival time for chlorfenapyr, but not for deltamethrin. Pyrethro id-resistant bed bugs also showed a similar increase in their survival time for chlorfenapyr after a bloodmeal. The comparison of mortality responses between fed and unfed bed bugs treated with similar amount of chlorfenapyr per fresh body weight indicated that increased body mass was not the primary cause for this bloodmeal-induced tolerance increase for chlorfenapyr. Because the surviving bed bugs can continue ovipositing, the effectiveness of chlorfenapyr residual deposits in bed bug harborages could be significantly affected by the feeding status of the adult bed bug populations.
The principal target of rapamycin‐induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain.

The immunosuppressive agent rapamycin induces inactivation of p70s6k with no effect on other mitogen‐activated kinases. Here we have employed a combination of techniques, including mass spectrometry, to demonstrate that this effect is associated with selective dephosphorylation of three previously unidentified p70s6k phosphorylation sites: T229, T389 and S404. T229 resides at a conserved position in the catalytic domain, whose phosphorylation is essential for the activation of other mitogen‐induced kinases. However, the principal target of rapamycin‐induced p70s6k inactivation is T389, which is located in an unusual hydrophobic sequence outside the catalytic domain. Mutation of T389 to alanine ablates kinase activity, whereas mutation to glutamic acid confers constitutive kinase activity and rapamycin resistance. The importance of this site and its surrounding motif to kinase function is emphasized by its presence in a large number of protein kinases of the second messenger family and its conservation in putative p70s6k homologues from as distantly related organisms as yeast and plants.