Pseudomonic acid derivatives from a marine bacterium

The spongeDarwinella rosacea was found to harbor a host of marine microorganisms. One of these bacteria was identified as a marineAlteromonas species. The organic extract of this bacterium was antimicrobial, and the activity was traced to two novel pseudomonic acid derivatives1 and7. The structures of these compounds were elucidated by interpretation of the spectral data and extensive use of 2-dimensional NMR techniques and NOE studies on the parent compounds and the acetate derivatives2 and8.     

Identification and seasonal quantification of defensive secretion components ofOreina gloriosa (Coleoptera: Chrysomelidae)

Tyrosine betaine, four new cardenolides (4, 5, 6, and7) and three known cardenolides (2, 3, and8) were isolated from the defensive secretion, of the leaf beetleOreina gloriosa and their chemical structure determined. 16 secretion components of individual beetles were quantified. Secretion composition of field-collected beetles was affected by season, sex and body weight.     

A new flavone glycoside from the fernPteris cretica

A new flavone glycoside isolated from the fernPteris cretica has been shown to be luteolin 7-O-robinobioside (1) by chemical and spectral methods. In addition luteolin 7-O-rutinoside (2) and luteolin 7-O-glucoside (3) have been isolated from this plant. Flavonoid2 is reported for the first time in ferns.     

4-Isothiocyanato-4′-nitrodiphenylamine (C9333-Go/CGP 4540) an anthelminthic with an unusual spectrum of activity against intestinal nematodes,filariae and schistosomes

Summary 4-isothiocyanato-4-nitrodiphenylamine was found to possess activity against intestinal nematodes in mice, against schistosomes in various hosts including primates and against two filarial species in the mongolian jird. Upon administration in a single oral dose it is equally effective againstS. haematobium, S. mansoni andS. japonicum.     

Chemotherapeutic effects of 4-isothiocyanato-4′-nitrodiphenylamine (C9333-Go/CGP 4540) on infections withNematospiroides dubius,Hymenolepis diminuta,Hymenolepis nana andSpirometra mansonoides

Summary 4-Isothiocyanato-4-nitrodiphenylamine possessed anthelmintic activity againstNippostrongylus dubius andHymenolepis nana in mice andH. diminuta in rats as determined by both egg counts and recovery of parasites at autopsy. No activity was detected against the cestode,Spirometra mansonoides, in cats.This investigation was supported in part by grants AI-10512 and AI-09483 from the National Institutes of Health. The authors are indebted to Dr P.P. Weinstein for providing animals infected withSpirometra mansonoides.     

3,5-Dibromo-2′-chloro-4′-isothiocyanatosalicylanilide,a potent anthelminitic

Summary The compound, 3,5-dibromo-2-chloro-4-isothiocyanatosalicylanilide, has been tested against various nematode and cestode parasites in experimental and domestric animals. It shoved 100% activity againstAncylostoma ceylanicum, A. tubaeformis, Syphacia obvelata, Ascaridia galli, Toxocara spp.,Toxascaris sp.,Gnathostoma spinigerum, Hymenolepis nana, Raillietina spp. andTaenia spp. in doses 25–70 mg/kg given in single or multiple administrations.Acknowledgments. We express sincere thanks to Dr Nitya Nand, F.N.A., CDRI, Lucknow, for his keen interest in the work, to Dr B. N. Dhawan, F.N.A. for providing informations about general pharmacology of the compound, and to Dr R. K. Chatterjee and Dr P. K. Murthy for carrying out antifilarial sreening. Technical assistance of Mr S. C. Bhar and Mr S. Ram is acknowledged.     

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5–20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of d-glucose was lower than d-fructose. However, uptake of d-glucose was higher than d-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection.     

Isaac Newton’s ‘Of Quadrature by Ordinates’

In Of Quadrature by Ordinates (1695), Isaac Newton tried two methods for obtaining the Newton–Cotes formulae. The first method is extrapolation and the second one is the method of undetermined coefficients using the quadrature of monomials. The first method provides $n$ -ordinate Newton–Cotes formulae only for cases in which $n=3,4$ and 5. However this method provides another important formulae if the ratios of errors are corrected. It is proved that the second method is correct and provides the Newton–Cotes formulae. Present significance of each of the methods is given.     

Pre-Euclidean geometry and Aeginetan coin design: some further remarks

Some ancient Greek coins from the island state of Aegina depict peculiar geometric designs. Hitherto they have been interpreted as anticipations of some Euclidean propositions. But this paper proposes geometrical constructions which establish connections to pre-Euclidean treatments of incommensurability. The earlier Aeginetan coin design from about 500 bc onwards appears as an attempt not only to deal with incommensurability but also to conceal it. It might be related to Plato’s dialogue Timaeus. The newer design from 404 bc onwards reveals incommensurability, namely in the context of ‘doubling the square’. It thereby covers the same topic but a different geometry as passages in Plato’s dialogue Meno (385 bc). This coin design incorporates important elements of ancient Greek geometrical analysis of the fifth century bc like the gnomon, Hippocrates’ squaring of the lunule (ca. 430 bc), and a geometrical version of monetary equivalence. Through this venue, the design’s conceptual lineage might be traced as far back as Heraclitus’ cosmology of about 500 bc.     

Investigations of the coordinates in Ptolemy’s Geographike Hyphegesis Book 8

In Book 8 of his Geographike Hyphegesis Ptolemy gives coordinates for ca. 360 so-called noteworthy cities. These coordinates are the time difference to Alexandria, the length of the longest day, and partly the ecliptic distance from the summer solstice. The supposable original conversions between the coordinates in Book 8 and the geographical coordinates in the location catalogue of Books 2–7 including the underlying parameters and tabulations are here reconstructed. The results document the differences between the ${\Omega}$ - and ${\Xi}$ -recension. The known difference in the longitude of Alexandria underlying the conversion of the longitudes is examined more closely. For the ecliptic distances from the summer solstice of the ${\Omega}$ -recension, it is revealed that they were originally computed by means of a so far undiscovered approximate, linear conversion. Further it is shown that the lengths of the longest day could be based on a linear interpolation of the data in the Mathematike Syntaxis 2.6.     

Wnt–Notch signalling crosstalk in development and disease

The Notch and Wnt pathways are two of only a handful of highly conserved signalling pathways that control cell-fate decisions during animal development (Pires-daSilva and Sommer in Nat Rev Genet 4: 39–49, 2003). These two pathways are required together to regulate many aspects of metazoan development, ranging from germ layer patterning in sea urchins (Peter and Davidson in Nature 474: 635–639, 2011) to the formation and patterning of the fly wing (Axelrod et al in Science 271:1826–1832, 1996; Micchelli et al in Development 124:1485–1495, 1997; Rulifson et al in Nature 384:72–74, 1996), the spacing of the ciliated cells in the epidermis of frog embryos (Collu et al in Development 139:4405–4415, 2012) and the maintenance and turnover of the skin, gut lining and mammary gland in mammals (Clayton et al in Nature 446:185–189, 2007; Clevers in Cell 154:274–284, 2013; Doupe et al in Dev Cell 18:317–323, 2010; Lim et al in Science 342:1226–1230, 2013; Lowell et al in Curr Biol 10:491–500, 2000; van et al in Nature 435:959–963, 2005; Yin et al in Nat Methods 11:106–112, 2013). In addition, many diseases, including several cancers, are caused by aberrant signalling through the two pathways (Bolós et al in Endocr Rev 28: 339–363, 2007; Clevers in Cell 127: 469–480, 2006). In this review, we will outline the two signalling pathways, describe the different points of interaction between them, and cover how these interactions influence development and disease.     

Heterogeneous responses of canine basilar and middle cerebral arteries to serotonin at normal and high CO2 tension

The responses of basilar arteries (BAs) to serotonin were attenuated by high \(P_{CO_2 } \) (86±1 mm Hg) and the pH matched acidotic solution ( \(P_{CO_2 } \) 37±1 mm Hg), whereas the responses of middle cerebral arteries (MCAs) were not. High \(P_{CO_2 } \) decreased the basal tone of both arteries, and the changes in basal tone due to high \(P_{CO_2 } \) were not influenced by 3×10^?7 M imipramine, 10^?5 M pargyline or 10^?4 M aspirin. The responses of BAs to serotonin were attenuated by high \(P_{CO_2 } \) in the presence of imipramine, pargyline and aspirin. The responses of MCAs to serotonin were not influenced by high \(P_{CO_2 } \) in the presence of pargyline and aspirin, but attenuated by high \(P_{CO_2 } \) in the presence of imipramine.     

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice

Introduction

Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals.

Results

Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots.

Conclusions

We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.     

The development of the Laplace transform, 1737–1937

This paper, the first of two, follows the development of theLaplace Transform from its earliest beginnings withEuler, usually dated at 1737, to the year 1880, whenSpitzer was its major, if himself relatively minor, protagonist. The coverage aims at completeness, and shows the state which the technique reached in the hands of its greatest exponent to that time,Petzval. A sequel will trace the development of the modern theory from its beginnings withPoincaré to its present form, due toDoetsch.