Temporally and spatially regulated somatic mutagenesis in mice

In mice transgenesis through oocyte injection or DNA recombination in embryonal stem (ES) cells allows mutations to be introduced into the germline. However, the earliest phenotype of the introduced mutation can eclipse later effects. We show in mice that site-specific genomic recombination can be induced in a selected cell type, B lymphocytes, at a chosen time. This precision of somatic mutagenesis was accomplished by limiting expression of a Cre recombinase-estrogen receptor fusion protein to B lymphocytes by use of tissue-specific elements in the promoter of the transgene employed. The expressed fusion protein remained inactive until derepressed by systemic administration of an exogenous ligand for the estrogen receptor, 4-OH-tamoxifen. Upon derepression the Cre recombinase enzyme deleted specific DNA segments, flanked by loxP sites, in B lymphocytes only. The efficiency of recombination in cells expressing the fusion protein could be varied from low levels to >80%, depending on the dose of ligand administered. Our work presents a paradigm applicable to other uses of site-specific recombination in somatic mutagenesis where both temporal and spatial regulation are desired

Studies of encephalitozoonosis in vervet monkeys (Cercopithecus pygerythrus) orally inoculated with spores of Encephalitozoon cuniculi isolated from dogs (Canis familiaris)

Encephalitozoonosis was induced in 35 of 38 vervet monkeys (Cercopithecus pygerythrus). They were either directly (orally) inoculated with Encephlitozoon cuniculi or indirectly exposed to this protozoan parasite. Cell-culture-grown spores of E. cuniculi, isolated from the kidneys of dogs with natural, fatal disease, were administered orally to 29 of these monkeys. Another 5 were exposed in utero by orally infecting pregnant females, and 3 were exposed to horizontal infection by nursing infected infants. Only one was given an intravenous inoculation of spores. The disease was induced in non-gravid and late-pregnant adults, immunocompetent infants, and in infants that were immunologically compromised by parenteral steroid administration, as well as in one infant that was immunologically immature because of its premature birth. The effects of age, dosage, post-inoculation (PI) interval, passage level of the parasite in cell culture and immunological status of the host were correlated with macroscopical and microscopical lesions. The experimentally induced infection was confirmed either by reisolation of the parasite in cell culture or by observation of spores in tissue sections. Both confirmatory methods were supported by serological examination. Reisolation of the organism in primary cell culture prepared from kidneys usually resulted in more frequent isolates and larger yields of spores from infants than from adult vervets. Infection with E. cuniculi invariably induced subclinical disease. Based on histology, lesions were minimal to moderately severe, depending on age, PI interval, and immunological status of the host. Alimentary tract infections were seen histologically as early as three days Pl. Subsequently, infections resulted in detectable lesions most consistently in the liver, kidneys and brain. Lesions in these organs were generally granulomatous and were similar to those found in canine encephalitozoonosis. In addition, multifocal interstitial pneumonitis and myocarditis as well as vasculitis and perivasculitis were seen in other tissues and organs. Infants had more severe and more widespread lesions than adults. Although lesions and spores were still present in the brain of one immunocompetent infant 36 weeks after initial infection, the disease in immunocompetent infants and adults is thought to be self-limiting. However, infection may persist. Immunological depression favoured increased growth and multiplication of the organism, and resulted in detection of more spores within inflammatory lesions as well as more intracellular colonies of the organism that were free of inflammatory reaction. Long-term growth of E. cuniculi in cell culture did not appear to alter its pathogenicity, nor did varying the numbers of spores (2 x 10⁶-3 x 10¹º) in the inoculum appear to influence the severity of the disease. Horizontal infection was readily established, and vertical transmission was demonstrated. Results of this study suggest that spores of E. cuniculi shed by dogs may become agents of latent infection and disease in vervets, and probably other nonhuman primates as well. It further seems probable that these spores may also be potential agents of latent zoonosis of man.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.lmchunu2014mn201

Ultrasoft Renormalization in Non-Relativistic QCD

For Non-Relativistic QCD the velocity renormalization group correlates the renormalization scales for ultrasoft, potential and soft degrees of freedom. Here we discuss the renormalization of operators by ultrasoft gluons. We show that renormalization of soft vertices can induce new operators, and also present a procedure for correctly subtracting divergences in mixed potential-ultrasoft graphs. Our results affect the running of the spin-independent potentials in QCD. The change for the NNLL t-tbar cross section near threshold is very small, being at the 1% level and essentially independent of the energy. We also discuss implications for analyzing situations where mv^2 ~ Lambda_QCD.Comment: 31 pages, 11 fig

Renormalization group analysis of the QCD quark potential to order v^2

A one-loop renormalization group analysis of the order v^2 relativistic corrections to the static QCD potential is presented. The velocity renormalization group is used to simultaneously sum ln(m/mv) and ln(m/mv^2) terms. The results are compared to previous calculations in the literature.Comment: 13 pages. important change: running of soft Lagrangian include

DC Josephson Effect in SNS Junctions of Anisotropic Superconductors

A formula for the Josephson current between two superconductors with anisotropic pairing symmetries is derived based on the mean-field theory of superconductivity. Zero-energy states formed at the junction interfaces is one of basic phenomena in anisotropic superconductor junctions. In the obtained formula, effects of the zero-energy states on the Josephson current are taken into account through the Andreev reflection coefficients of a quasiparticle. In low temperature regimes, the formula can describe an anomaly in the Josephson current which is a direct consequence of the exsitence of zero-energy states. It is possible to apply the formula to junctions consist of superconductors with spin-singlet Cooper pairs and those with spin-triplet Cooper pairs

Spinor Field in Bianchi type-I Universe: regular solutions

Self-consistent solutions to the nonlinear spinor field equations in General Relativity has been studied for the case of Bianchi type-I (B-I) space-time. It has been shown that, for some special type of nonliearity the model provides regular solution, but this singularity-free solutions are attained at the cost of broken dominant energy condition in Hawking-Penrose theorem. It has also been shown that the introduction of $\Lambda$-term in the Lagrangian generates oscillations of the B-I model, which is not the case in absence of $\Lambda$ term. Moreover, for the linear spinor field, the $\Lambda$ term provides oscillatory solutions, those are regular everywhere, without violating dominant energy condition. Key words: Nonlinear spinor field (NLSF), Bianch type -I model (B-I), $\Lambda$ term PACS 98.80.C CosmologyComment: RevTex, 21 page

Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells

Differentiation and lineage specification are controlled by cooperation of growth factor signalling. The involvement of epigenetic regulators in lineage specification remains largely elusive. Here, we show that the histone methyltransferase Mll1 prevents intestinal progenitor cells from differentiation, whereas it is also involved in secretory lineage specification of Paneth and goblet cells. Using conditional mutagenesis in mice and intestinal organoids, we demonstrate that loss of Mll1 renders intestinal progenitor cells permissive for Wnt-driven secretory differentiation. However, Mll1-deficient crypt cells fail to segregate Paneth and goblet cell fates. Mll1 deficiency causes Paneth cell-determined crypt progenitors to exhibit goblet cell features by unleashing Mapk signalling, resulting in increased numbers of mixed Paneth/goblet cells. We show that loss of Mll1 abolishes the pro-proliferative effect of Mapk signalling in intestinal progenitor cells and promotes Mapk-induced goblet cell differentiation. Our data uncover Mll1 and its downstream targets Gata4/6 as a regulatory hub of Wnt and Mapk signalling in the control of lineage specification of intestinal secretory Paneth and goblet cells

B-->pi and B-->K transitions in standard and quenched chiral perturbation theory

We study the effects of chiral logs on the heavy-->light pseudoscalar meson transition form factors by using standard and quenched chiral perturbation theory combined with the static heavy quark limit. The resulting expressions are used to indicate the size of uncertainties due to the use of the quenched approximation in the current lattice studies. They may also be used to assess the size of systematic uncertainties induced by missing chiral log terms in extrapolating toward the physical pion mass. We also provide the coefficient multiplying the quenched chiral log, which may be useful if the quenched lattice studies are performed with very light mesons.Comment: 33 pages, 8 PostScript figures, version to appear in PR

Polyphenols journey through blood-brain barrier towards neuronal protection

Age-related complications such as neurodegenerative disorders are increasing and remain cureless. The possibility of altering the progression or the development of these multifactorial diseases through diet is an emerging and attractive approach with increasing experimental support. We examined the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to infuence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for diferential transport, likely related to chemical structure. Moreover, endothelial metabolism of these phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies. Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and infammatory injuries and this attenuation of neuroinfammation was achieved via modulation of NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary (poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated infammation and exert neuroprotective efects, with potential for alleviation of neurodegenerative diseases.info:eu-repo/semantics/publishedVersio

What is a β cell? - Chapter I in the Human Islet Research Network (HIRN) review series

BACKGROUND: The pancreatic β cell, as the sole source of the vital hormone insulin, has been under intensive study for more than a century. Given the potential of newly created insulin-producing cells as a treatment or even cure of type 1 diabetes (T1D) and possibly in severe cases of type 2 diabetes (T2D), multiple academic and commercial laboratories are working to derive surrogate glucose-responsive, insulin-producing cells. SCOPE OF REVIEW: The recent development of advanced phenotyping technologies, including molecular, epigenomic, histological, or functional, have greatly improved our understanding of the critical properties of human β cells. Using this information, here we summarize the salient features of normal, fully functional adult human β cells, and propose minimal criteria for what should rightfully be termed 'β cells' as opposed to insulin-producing but not fully-functional surrogates that we propose should be referred to as 'β-like' cells or insulin-producing cells. MAJOR CONCLUSIONS: Clear criteria can be established to differentiate fully functional, mature β cells from 'β-like' surrogates. In addition, we outline important knowledge gaps that must be addressed to enable a greater understanding of the β cell