Effect of riboflavin deficiency on in vivo incorporation of C14 from labelled alanine into liver glycogen

Zusammenfassung Männliche Albino-Ratten, die während 45 Tagen mit Riboflavin-armer Kost ernährt wurden, zeigten erhöhten Glykogengehalt in der Leber, verbunden mit einer gesteigerten Aufnahme von C¹⁴ aus Alanin-1-C¹⁴ im Leberglykogen. Die Befunde lassen auf erhöhte Glykoneogenese in der Leber Riboflavin-armer Ratten schliessen.     

Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin

Genetically encoded antibiotic peptides are evolutionarily ancient and widespread effector molecules of immune defence. Mammalian defensins, one subset of such peptides, have been implicated in the antimicrobial defence capacity of phagocytic leukocytes and various epithelial cells, but direct evidence of the magnitude of their in vivo effects have not been clearly demonstrated. Paneth cells, specialized epithelia of the small intestinal crypt, secrete abundant alpha-defensins and other antimicrobial polypeptides including human defensin 5 (HD-5; also known as DEFA5). Although antibiotic activity of HD-5 has been demonstrated in vitro, functional studies of HD-5 biology have been limited by the lack of in vivo models. To study the in vivo role of HD-5, we developed a transgenic mouse model using a 2.9-kilobase HD-5 minigene containing two HD-5 exons and 1.4 kilobases of 5'-flanking sequence. Here we show that HD-5 expression in these mice is specific to Paneth cells and reflects endogenous enteric defensin gene expression. The storage and processing of transgenic HD-5 also matches that observed in humans. HD-5 transgenic mice were markedly resistant to oral challenge with virulent Salmonella typhimurium. These findings provide support for a critical in vivo role of epithelial-derived defensins in mammalian host defence.     

Entangled quantum state of magnetic dipoles

Free magnetic moments usually manifest themselves in Curie laws, where weak external magnetic fields produce magnetizations that vary as the reciprocal of the temperature (1/T). For a variety of materials that do not display static magnetism, including doped semiconductors and certain rare-earth intermetallics, the 1/T law is replaced by a power law T(-alpha) with alpha < 1. Here we show that a much simpler material system-namely, the insulating magnetic salt LiHo(x)Y(1-x)F(4)-can also display such a power law. Moreover, by comparing the results of numerical simulations of this system with susceptibility and specific-heat data, we show that both energy-level splitting and quantum entanglement are crucial to describing its behaviour. The second of these quantum mechanical effects-entanglement, where the wavefunction of a system with several degrees of freedom cannot be written as a product of wavefunctions for each degree of freedom-becomes visible for remarkably small tunnelling terms, and is activated well before tunnelling has visible effects on the spectrum. This finding is significant because it shows that entanglement, rather than energy-level redistribution, can underlie the magnetic behaviour of a simple insulating quantum spin system.     

Division ofEntamoeba invadens Rodhain, 1934, in cultures

Zusammenfassung BeiEntamoeba invadens wurde eine ungleiche zellplasmatische Teilung beobachtet. Ein entsprechender Teilungsmodus gilt auch fürE. ranarum undE. moshkovskii.

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This work was done in the Department of Zoology, University of London, King's College, London WC2, England.     

Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function

Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.     

Role of phospholipid transfer protein in rabbit lung development

A 36-kDa phospholipid transfer protein (PLT-P_R), which preferentially transfers phosphatidyl choline (PC) compared to phosphatidyl inositol (PI), was purified 827-fold from rabbit lung homogenate. Incorporation of cholesterol in unilamellar vesicles reduced the PC transfer activity of PLTP_R. Dipalmitoyl phosphatidyl choline uptake by alveolar type II cells was increased in the presence of the protein, and further enhanced in the presence of surfactant liposomes. However, a decrease in uptake was noted with cholesterol in host membranes. Incorporation of PI into host membranes had a low stimulatory effect on the process. All these effects were more pronounced in adult type II cells compared to premature, term and 3-day-old pups. Received 12 September 2001; accepted 11 October 2001     

TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer

The existence of tumor-suppressor genes was originally demonstrated by functional complementation through whole-cell and microcell fusion. Transfer of chromosome 11 into a human non-small-cell lung cancer (NSCLC) cell line, A549, suppresses tumorigenicity. Loss of heterozygosity (LOH) on the long arm of chromosome 11 has been reported in NSCLC and other cancers. Several independent studies indicate that multiple tumor-suppressor genes are found in this region, including the gene PPP2R1B at 11q23-24 (ref. 7). Linkage studies of NSCLC are precluded because no hereditary forms are known. We previously identified a region of 700 kb on 11q23.2 that completely suppresses tumorigenicity of A549 human NSCLC cells. Most of this tumor-suppressor activity localizes to a 100-kb segment by functional complementation. Here we report that this region contains a single confirmed gene, TSLC1, whose expression is reduced or absent in A549 and several other NSCLC, hepatocellular carcinoma (HCC) and pancreatic cancer (PaC) cell lines. TSLC1 expression or suppression is correlated with promoter methylation state in these cell lines. Restoration of TSLC1 expression to normal or higher levels suppresses tumor formation by A549 cells in nude mice. Only 2 inactivating mutations of TSLC1 were discovered in 161 tumors and tumor cell lines, both among the 20 primary tumors with LOH for 11q23.2. Promoter methylation was observed in 15 of the other 18 primary NSCLC, HCC and PaC tumors with LOH for 11q23.2. Thus, attenuation of TSLC1 expression occurred in 85% of primary tumors with LOH. Hypermethylation of the TSLC1 promoter would seem to represent the 'second hit' in NSCLC with LOH.     

GTP-activated communication between distinct inositol 1,4,5-trisphosphate-sensitive and -insensitive calcium pools

Inositol 1,4,5-trisphosphate (InsP3) is an established mediator of intracellular Ca2+ signals but little is known of the nature and organization of Ca2+ regulatory organelles responsive to InsP3. Here we derive new information from the study of Ca2+ movements induced both by InsP3 and a specific GTP-activated Ca2+ translocation process. The latter mechanism is clearly distinct from that activated by InsP3 and may involve the translocation of Ca2+ between compartments without its release into the cytosol. This idea is supported by the fact that GTP activates Ca2+ movement into the InsP3-releasable pool. In the light of this evidence we postulated that there are two intracellular Ca2+ pools distinguishable by InsP3-sensitivity and oxalate-permeability, and that movement between them is activated by GTP. We report here direct evidence for the existence and separation of two distinct Ca2+-pumping compartments with properties coinciding with those predicted. Of these, the InsP3-sensitive Ca2+ pool is identified within a purified rough endoplasmic reticulum fraction, an observation consistent with recent InsP3 receptor-localization studies. Ca2+ translocation between pools may reflect function of a class of small GTP-binding proteins known to mediate interorganelle transfer in eukaryotic cells.     

Testicular Leydig cells and 277-1277-1277-1dehydrogenase in cadmium-treated toads (Bufo melanostictus)

Summary Injection of cadmium chloride in toad increased Leydig cell size (area) and ₅-3-hydroxysteroid dehydrogenase activity in the testis.Acknowledgments. We would like to express our thanks to Dr C. Deb, Head of the Department of Physiology, Calcutta University, for his constant encouragement and Mr R. K. Bhattacharya, Microphotographer, Department of Physiology, for his kind cooperation. This work was supported by U. G. C. Teachers' Grants, New Delhi.