Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleophile Selectivity of Chorismate‐Utilizing Enzymes

aeruginosa) catalyzes the conversion of chorismate to isochorismate (2) by nucleophilic addition of water to the C2 of chorismate, with loss of the C4 hydroxyl. This is then converted to salicylate (3) by isochorismate pyruvate lyase (e.g. , PchB in P. aeruginosa). Very recently we described a bifunctional salicylate synthase (Irp9 from Yersinia enterocolitica) that converts chorismate into salicylate via isochorismate. This two-step transformation is analogous to the formation of anthranilate from chorismate catalyzed by the TrpE subunit of anthranilate synthase. The TrpE mechanism involves initial addition of ammonia to the C2 of chorismate to form 2-amino-2-deoxyisochorismate (ADIC; 4), followed by elimination of the enol pyruvate side-chain to form anthranilate (5). The factors that control the identity of the nucleophile in the Irp9 and TrpE reactions are unknown, and are the focus of this Communication. Although there is only approximately 20% amino acid sequence identity between PchA, Irp9 and TrpE, examination of the crystal structures of TrpE, and Irp9 shows that they are structurally homologous. Active sites from Serratia marcescens TrpE structure (in which benzoate and pyruvate are bound) and the recently solved Irp9 structure (with salicylate and pyruvate bound) are almost identical (Figure 1). The key catalytic residues are strictly conserved and superimposed. The only significant difference is the identity of the residue 5.5 : away from the C2 of salicylate in the Irp9 products complex. This is lysine in Irp9 (K193) and PchA (K221), which both catalyze nucleophilic attack by water, but glutamine in TrpE (Q262), for which ammonia is the nucleophile. In the absence of any other structural clues as to the factors involved in nucleophile selection, this residue was mutated. Accordingly, the Irp9 and the TrpE/TrpG mutants as well as their respective ACHTUNGTRENNUNGalanine substitutions Irp9 and TrpE/TrpG were constructed and over-expressed as hexahistidine-tagged enzymes in E. coli. The mutants were studied by H NMR spectroscopy to determine the nature of the products formed (Table 1). Control experiments with wild-type enzymes showed that Irp9 forms salicylate, independent of the presence of NH4Cl (Figure 2D), and that anthranilate synthase forms anthranilate in the presence of NH4Cl (Figure 2G) but neither anthranilate or salicylate in the absence of NH4Cl (Figure 2H). The Irp9 mutant does not form salicylate (Figure 2E), but does form anthranilate in the presence of NH4Cl (Figure 2F). By using a fluorescence assay to
Does the cycle of rerestoration lead to larger restorations?

The common practice of rerestoring teeth has been termed the "cycle of rerestoration. " Some researchers and clinicians have speculated that this cycle results in teeth receiving progressively larger restorations. In this study involving 1,337 decisions to replace existing restorations in posterior teeth, the authors noted that 70 percent of all recommendations resulted in an increased number of restored surfaces. This observed increase in restoration size raises questions about the effects of the rerestoration cycle on the health of a tooth and suggests that practitioners should attempt to avoid premature rerestoration since it could hasten the cycle.
Jung’s transcendent function as Nietzsche’s will to power and eternal recurrence of the same

This article will retrieve Heidegger’s interpretation on Nietzsche’s Will to Power and a phenomenological interpretation of Jung’s writing on complexes and the Rosarium Philosophorum to project a new meaning to explain Jung’s transcendent function. By the end of this article, the reader should have gained a more detailed and specific description of complexes, the Rosarium Philosophorum and the transcendent function because further aspects of the phenomenology and ontology have been highlighted which includes understanding the transcendent function as Nietzsche’s Will to Power.
Relevance of Seizure‐Induced Neurogenesis in Animal Models of Epilepsy to the Etiology of Temporal Lobe Epilepsy

Summary: Seizure induction in laboratory animals is followed by many changes in structure and function, and one of these is an increase in neurogenesis—the birth of new neurons. This phenomenon may be relevant to temporal lobe epilepsy (TLE), because one of the regions of the brain where seizure‐induced neurogenesis is most robust is the dentate gyrus—an area of the brain that has been implicated in the pathophysiology of TLE. Although initial studies predicted that neurogenesis in the dentate gyrus would be important to normal functions, such as learning and memory, the new neurons that are born after seizures may not necessarily promote normal function. There appears to be a complex functional and structural relationship between the new dentate gyrus neurons and preexisting cells, both in the animal models of TLE and in tissue resected from patients with intractable TLE. These studies provide new insights into the mechanisms of TLE, and suggest novel strategies for intervention that could be used to prevent or treat TLE.
Growth performance and carcass characteristics of central highland goats in Sekota District, Ethiopia.

On farm monitoring ofcentral highland goats were conducted in Sekota district of the Amhara regionalstate, Ethiopia to evaluate the growth performances under the traditionalmanagement practices. On farm feeding trial was also conducted to see thefeeding performances and carcass characteristics of Central Highland goattypes. Data used for the study was collected from randomly selected on-farmflocks for two years. Yearling bucks were assigned randomly in to two feedtypes: grazing only and grazing plus concentrate. The overall mean birthweight, weaning weight and yearling weight obtained were 2.01±0.03, 9.02±0.18and 20.61±0.74 kg, respectively. All the fixed effects considered weresignificantly affected birth weight and weaning weight. However, at yearling age,parity and type of birth were not significant. Kids from larger parity does,single born kids, male kids and kids born in the wet and cool season had higher(p<0.001) birth and weaning weights from their group. Male kids and kidsborn in the dry season had heavier weight than female and wet season born kids.The overall mean pre- and post- weaning growth rate obtained were 76.6±2.3 and42.8±2.9 g/day, respectively. Kids born from later parity does, single and kidsborn at wet season had higher (P<0.001) pre-weaning growth rates than kidsborn from first parity, as twins and kids born during hot dry season,respectively. The overall mean final body weights of goats from the feedingtrial were 28.7 and 30.8 kg for the control and supplemented groups, respectively.Even though, there were numerical differences on final body weight and carcassparameters, there was no significant difference between supplemented and nonsupplemented groups of yearling bucks. Central Highland goat in this studyshowed better growth performances than most of the goat breeds in Ethiopia. Thesignificant effect of fixed effects needs to be considered in developingbreeding strategy for the breed. Moreover, integrated efforts combining thefeed, breeding and health aspects of production are very important to make useof the breed.
Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure.

UNLABELLED Serum-free insulin-like growth factor I correlates with clearance in patients with chronic renal failure. BACKGROUND Chronic renal failure (CRF) results in major changes in the circulating growth hormone (GH)/insulin-like growth factor (IGF) system. However, there are only limited data on changes in free IGF-I in CRF. METHODS Matched groups of nondiabetic, nondialyzed patients with CRF (N = 25) and healthy controls (N = 13) were compared. The creatinine clearance (CCr) based on a 24-hour urine collection ranged from 3 to 59 and 89 to 148 ml/min/1.73 m2 in patients and controls, respectively. Overnight fasting serum samples were analyzed for free and total IGF-I and -II, and IGF-binding protein (IGFBP)-1, -2, and -3. Additionally, intact as well as proteolyzed IGFBP-3 was determined. RESULTS The patients had reduced serum-free IGF-I (-53%) and increased levels of total IGF-II (40%), IGFBP-1 (546%), and IGFBP-2 (270%, P < 0.05). Serum total IGF-I and free IGF-II were normal. Also, serum levels of immunoreactive IGFBP-3 were elevated (33%, P < 0.05), but this could be explained by an increased abundance of IGFBP-3 fragments, as ligand blotting showed no difference in levels of intact IGFBP-3. Accordingly, patients had an increased proteolysis of IGFBP-3 in vivo (17%) and in vitro (7%, P < 0.05). In patients, free IGF-I levels correlated positively with CCr (r2 = 0.38, P < 0.002) and inversely with IGFBP-1 (r2 = 0.69, P < 0. 0001) and IGFBP-2 (r2 = 0.41, P < 0.0007), whereas CCr was inversely correlated with levels of IGFBP-1 (r2 = 0.48, P < 0.0001) and IGFBP-2 (r2 = 0.63, P < 0.0001). CONCLUSIONS These data strongly support the hypothesis that CRF-related growth failure and tissue catabolism are caused by an increased concentration of circulating IGFBP-1 and -2, resulting in low serum levels of free IGF-I and thus IGF-I bioactivity. In addition, low levels of free IGF-I may explain the increased secretion of GH in CRF.
Standardized protocol for a depletion of intramyocellular lipids (IMCL)

Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels.
A retrospective six-year national survey of P. multocida infections in Israel

Pasteurella multocida is the commonest organism infecting pet bites. Anecdotal reports tend to overemphasize dramatic outcomes. We aimed to study a large database of P. multocida infections. This retrospective survey of P. multocida infections in Israeli hospitals refers to the y 2000–2005. Clinical microbiologists were contacted by email and asked to perform a back-search of their hospital's records for isolates of P. multocida. The charts of patients growing P. multocida were abstracted into a structured questionnaire. 77 cases were identified in 12 hospitals, yielding an annual incidence of 0.19/100,000. The mean age was 49.2±26.5 y and the mortality rate was 2.6%. Those who died were >65 y of age, had diabetes mellitus or cirrhosis and were bacteraemic. One-third of the cases occurred in people aged ≥65 y. Cats caused most of these infections (54%). Surgery for debridement was common (53.7%), but no-one required amputation; a second- and third-look operation was necessary for these patients. Bacteraemia was found in 32.5% of patients and was significantly more common among those aged >60 y (p =0.044). Hospitalized patients with P. multocida have a favourable prognosis, apart from elderly and bacteraemic patients with comorbidities. Surgery and reoperations may be required in about half of the patients.
Salivary-agglutinin-mediated adherence of Streptococcus mutans to early plaque bacteria

Interspecies binding is important in the colonization of the oral cavity by bacteria. Streptococcus mutans can adhere to other plaque bacteria, such as Streptococcus sanguis and Actinomyces viscosus, and this adherence is enhanced by saliva. The salivary and bacterial molecules that mediate this interaction were investigated. Salivary agglutinin, a mucinlike glycoprotein known to mediate the aggregation of many oral streptococci in vitro, was found to mediate the adherence of S. mutans to S. sanguis or A. viscosus. Adherence of S. mutans to saliva- or agglutinin-coated S. sanguis and A. viscosus was inhibited by antibodies to the bacterial agglutinin receptor. Expression of the S. sanguis receptor (SSP-5) gene in Enterococcus faecalis increased adhesion of this organism to saliva- or agglutinin-coated S. sanguis and A. viscosus. This interaction could be inhibited by antibodies to the agglutinin receptor. The results suggest that salivary agglutinin can promote adherence of S. mutans to S. sanguis and A. viscosus through interactions with the agglutinin receptor on S. mutans.
Antimicrobial activity of crude epicarp and seed extracts from mature avocado fruit (Persea americana) of three cultivars

The epicarp and seed of Persea Americana Mill. var. Hass (Lauraceae), Persea Americana Mill. var. Shepard, and Persea americana Mill. var Fuerte cultivars of mature avocados (n = 3) were ground separately and extracted with both absolute ethanol and distilled water. Extracts were analyzed for antimicrobial activity using the microtiter broth microdilution assay against four Gram-positive bacteria, six Gram-negative bacteria, and one yeast. Antimicrobial activity against two molds was determined by the hole plate method. The ethanol extracts showed antimicrobial activity (104.2–416.7 μg/mL) toward both Gram-positive and Gram-negative bacteria (except Escherichia coli), while inhibition of the water extracts was only observed for Listeria monocytogenes (93.8–375.0 μg/mL) and Staphylococcus epidermidis (354.2 μg/mL). The minimum concentration required to inhibit Zygosaccharomyces bailii was 500 μg/mL for the ethanol extracts, while no inhibition was observed for the water extracts. No inhibition by either ethanol or water extracts was observed against Penicillium spp. and Aspergillus flavus.
Signal-to-noise ratio of modulated sources of ASE transmitted over dispersive fiber

We investigate, both theoretically and experimentally, the signal-to-noise ratio (SNR) of modulated amplified spontaneous emission (ASE) transmitted over dispersive fiber. We observe two significant effects; firstly, the signal-to-excess-noise ratio (SNR/sub ex/) varies across the pulse reaching its maximum value near the peak of the detected signal; and secondly, this maximum value decreases with increasing fiber dispersion-induced pulse broadening. Accurate calculation of transmission performance of high bit-rate optical communication systems employing ASE sources, such as spectrum slicing, requires inclusion of these effects.
Palaeogeography and palaeoecology of early Floian (Early Ordovician) cephalopods from the Upper Fezouata Formation, Anti-Atlas, Morocco

Abstract. In the central Anti-Atlas (Morocco), the Early Ordovician succession consists of about 1000 m of fossiliferous argillites and siltstones. The Upper Fezouata Formation (Floian) contains a comparatively rich and abundant cephalopod association. A small collection of these cephalopods is described herein for the first time. The cephalopods are interpreted as autochthonous or parautochthonous, representing a fauna, which originally lived nektobenthically in the open water above the sediments or related to the sea bottom. The cephalopod associations of the Upper Fezouata Formation are similar to other contemporaneous assemblages known from higher palaeolatitudes and associated with deeper depositional settings and in siliciclastically dominated deposits. They are composed almost exclusively of slender orthocones, in this case predominantly of Destombesiceras zagorense n. gen., n. sp. , which is interpreted as an early discosorid. Bathmoceras australe Teichert, 1939 and Bathmoceras taichoutense n. sp. from the Upper Fezouata Formation are at present the earliest unambiguous occurrences of bathmocerid cephalopods. Epizoans on the shell of a specimen of Rioceras are the earliest evidence of bryozoans growing as potential hitchhikers on cephalopod shells, indicating an early exploitation of a pseudoplanktonic lifestyle in this phylum. doi: 10.1002/mmng.201200004
Clinical relevance of Acinetobacter baumannii ventilator-associated pneumonia.

despite a relatively simple atomic structure, acts selectively by blocking the N-methyl-D-aspartate receptor. Because N-methyl-D-aspartate receptor antagonists are known to possess neuroprotective properties, a first study in rats was performed to investigate possible neuroprotection. During cardiopulmonary bypass surgery, neuroprotection of xenon was confirmed. The protective effect of xenon in animals is seen in subanaesthetic concentrations. In an unpublished study by our group, when cardiopulmonary resuscitation was performed in pigs, xenon reduced damage to the central nervous system (T. Marx, unpublished data). The use of xenon therefore is proposed in procedures where potential central nervous impairment is expected, including cardiac bypass surgery, cerebral trauma, and stroke (8). Prolonged ICU stay due to neuronal damage after cardiac bypass surgery alone is regarded to cost $2– 4 billion in the United States annually (9). The cost/benefit relationship, which in the view of other authors limits xenon’s use in anesthesia (4), therefore must be considered. Cost reduction by minimizing cerebral damage and reducing the length of ICU stay must been taken into consideration. Xenon’s use during ICU therapy can be expected in the near future, if further studies confirm the results of the animal experiments. Regarding this, the work of Dr. Bedi et al. (10), published in this issue of Critical Care Medicine, is overdue concerning the future of xenon. The application for ICU sedation was found to be feasible when using a closed ventilator system. The authors explain that in addition to the well-known properties like rapid recovery and hemodynamic stability, in closed-system anesthesia the requirements for the substance are reduced dramatically when all tissues are saturated. The inhaled concentrations used for sedation are below the concentration of xenon used in anesthesia (approximately 70%) (10). It is an important milestone for xenon’s future to demonstrate how xenon could be administered during ICU therapy. I regret that the authors did not measure the real xenon usage to give a rough estimation of the expected costs. Regarding closed-system ventilation during ICU therapy, some further studies have to be kept in mind regarding the accumulation of volatile compounds in breathing systems. High concentrations of possibly toxic compounds must be avoided. Under physiologic conditions, human breath contains 100 gaseous and volatile substances (11). This composition of human exhaled breath could be changed totally under conditions of severe organ failure. During conditions like sepsis or multiple organ failure, this might be a problem whose importance could not be assessed until now (12). Thomas Marx, MD Department of Cardiac Anaesthesia University of Ulm Ulm, Germany
Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial.

OBJECTIVE To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. INTERVENTIONS Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. MEASUREMENTS AND MAIN RESULTS The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. CONCLUSIONS The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.
Overexpression of the MTA1 gene in gastrointestinal carcinomas: Correlation with invasion and metastasis

The mta1 gene is a recently identified novel candidate metastasis‐associated gene. The deduced amino acid sequence contains an src homology‐3 domain binding motif, a zinc finger motif and possible phosphorylation sites, suggesting that this gene is involved in signal transduction or regulation of gene expression. The purpose of our study was to examine the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in colorectal and gastric carcinomas and thus to evaluate the relevance of the expression of this gene to human carcinoma progression. The expression of MTA1 mRNA in 36 colorectal and 34 gastric carcinoma samples was compared with that in corresponding normal mucosa tissues by semi‐quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) and the results were compared with clinico‐pathologic data. A relative overexpression of MTA1 mRNA (tumor/normal ratio ≥2) was observed in 14 of 36 (38.9%) colorectal carcinomas and 13 of 34 (38.2%) gastric carcinomas. Clinico‐pathologic correlations demonstrated that in colorectal carcinomas, tumors overexpressing MTA1 mRNA exhibited a significantly deeper wall invasion and a higher rate of metastasis to lymph nodes, and tended to be at an advanced Dukes' stage with frequent lymphatic involvement. In gastric carcinomas, the tumors overexpressing MTA1 mRNA showed significantly higher rates of serosal invasion and lymph node metastasis and tended to have a higher rate of vascular involvement. Our data suggest that overexpression of the MTA1 gene correlates with tumor invasion and the presence of metastases and that a high expression of MTA1 mRNA may be a potential indicator for assessing the malignant potential of colorectal and gastric carcinomas. Int. J. Cancer 74:459–463, 1997. © 1997 Wiley‐Liss, Inc.