Defects in Actin Dynamics Lead to an Autoinflammatory Condition through the Upregulation of CXCL5

Destrin (DSTN) is a member of the ADF/cofilin family of proteins and is an important regulator of actin dynamics. The primary function of destrin is to depolymerize filamentous actin into its monomeric form and promote filament severing. While progress has been made in understanding the biochemical functions of the ADF/cofilin proteins, the study of an animal model for cells deficient for DSTN provides an opportunity to investigate the physiological processes regulated by proper actin dynamics in vivo. A spontaneous mouse mutant, corneal disease 1(corn1), is deficient for DSTN, which causes epithelial hyperproliferation and neovascularization in the cornea. Dstn(corn1) mice exhibit an actin dynamics defect in the cornea as evidenced by the formation of actin stress fibers in the epithelial cells. Previously, we observed a significant infiltration of leukocytes into the cornea of Dstn(corn1) mice as well as the upregulation of proinflammatory molecules. In this study, we sought to characterize this inflammatory condition and explore the physiological mechanism through which a loss of Dstn function leads to inflammation.Through immunofluorescent analyses, we observed a significant recruitment of neutrophils and macrophages to the Dstn(corn1) cornea, demonstrating that the innate immune system is spontaneously activated in this mutant. The inflammatory chemokine, CXCL5, was ectopically expressed in the corneal epithelial cells of Dstn(corn1) mice, and targeting of the receptor for this chemokine inhibited neutrophil recruitment. An inflammatory reaction was not observed in the cornea of allelic mutant strain, Dstn(corn1-2J), which has a milder defect in actin dynamics in the corneal epithelial cells.This study shows that severe defects in actin dynamics lead to an autoinflammatory condition that is mediated by the expression of CXC chemokines

Marker-aided genetic stock management: prospects in Philippine aquatic biodiversity conservation and aquaculture

With the advent of DNA marker-based technologies and applications, genetic stock assessment incorporating molecular marker information has become an important tool in managing resources both for aquaculture and stock enhancement. Local initiatives toward this end have been undertaken by several research and academic agencies particularly those with access to advanced molecular genetic laboratory facilities both in the Philippines and in collaborating foreign institutions. Funds coming from the Philippine Department of Science and Technology and/or international research grants have supported work on commercially valuable species such as tilapia, shrimp, mud crabs, abalone, milkfish and some high value marine fishes with a view of utilizing and in the process, demonstrating the significance of more scientific microlevel assessment of stocks. Information drawn from marker-aided genetic stock evaluation can contribute to a better understanding of the impact of how proper stock management can be more effectively achieved and how this method can gradually translate to improved yields both from culture and fisheries. This paper covers a review of the status of this technology as applied to ongoing fish conservation and aquaculture production efforts in the Philippines

Gauge-independent transition separating confinement-Higgs phase in the lattice SU(2) gauge-fundamental scalar model

According to the conventional studies, the lattice SU(2) gauge-scalar model with a single scalar field in the fundamental representation of the gauge group has a single confinement-Higgs phase where Confinement and Higgs regions are subregions of an analytically continued single phase and there are no thermodynamic phase transitions, which is a well-known consequence of the Osterwalder-Seiler-Fradkin-Shenker theorem. In this paper, however, we show that we can define new type of gauge-invariant operators by combining the original fundamental scalar field and the so-called color-direction field which is obtained by change of field variables based on the gauge-covariant decomposition of the gauge field due to Cho-Duan-Ge-Shabanov and Faddeev-Niemi. By performing the numerical simulations on the lattice without any gauge fixing, we find a new transition line detected by the new gauge-invariant operators which completely separate the confinement-Higgs phase into two parts, confinement phase and the Higgs phase, in the strong gauge coupling, while it agrees with the conventional thermodynamic transition line in the weak gauge coupling. All results are obtained in the gauge-independent way, since no gauge fixing has been imposed in the numerical simulations. Moreover, we give a physical interpretation for the new transition from the viewpoint of the realization of a global symmetry.Comment: Discussions and simulation results improved. 28 pages, 15 figure

New gauge-independent transition separating confinement-Higgs phase in the lattice gauge-fundamental scalar model

The lattice gauge-scalar model with the scalar field in the fundamental representation of the gauge group has a single confinement-Higgs phase which is well-known as the Fradkin-Shenker-Osterwalder-Seiler analytic continuity theorem: Confinement and Higgs regions are subregions of an analytically continued single phase and there are no thermodynamics phase transitions between them. In this talk, however, we show that we can define new type of operators which enable to separate completely the confinement phase and the Higgs phase. In fact, they are constructed in the gauge-invariant procedure by combining the original scalar field and the so-called color-direction field which is obtained by change of field variables based on the gauge-covariant decomposition of the gauge field due to Cho-Duan-Ge-Shabanov and Faddeev-Niemi. We perform the numerical simulations for the model with SU(2) gauge group without any gauge fixing and find a new transition line which agrees with the conventional thermodynamic transition line in the weak gauge coupling and divides the confinement-Higgs phase into two separate phases, confinement and the Higgs, in the strong gauge coupling. All results are obtained in the gauge-independent way, since no gauge fixing has been imposed in the numerical simulations. Moreover, we give a physical interpretation for the new transition from the viewpoint of the spontaneous breaking of a global symmetry. This talk is based on the preprint [1].Comment: 9 pages, 5 figures, Talk presented at the 40th International Symposium on Lattice Field Theory (LATTICE2023), July 31-August 4, 2023 at Fermila

A third glucose uptake bypass in Corynebacterium glutamicum ATCC 31833

In Corynebacterium glutamicum, the phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) has long been the only known glucose uptake system, but we recently found suppressor mutants emerging from a PTS-negative strain of C. glutamicum ATCC 31833 on glucose agar plates, and identified two alternative potential glucose uptake systems, the myo-inositol transporters encoded by iolT1 and iolT2. The expression of either gene renders the PTS-negative strain WT Delta ptsH capable of growing on glucose. In the present study, we found a suppressor strain that still grew on glucose even after the iolT1 and iolT2 genes were both disrupted under the PTS-negative background. Whole-genome sequencing of the suppressor strain SPH1 identified a G-to-T exchange at 134 bp upstream of the bglF gene encoding an EII component of the beta-glucoside-PTS, which is found in limited wild-type strains of C. glutamicum. Introduction of the mutation into strain WT Delta ptsH allowed the PTS-negative strain to grow on glucose. Reverse transcription-quantitative PCR analysis revealed that the mutation upregulates the bglF gene by approximately 11-fold. Overexpression of bglF under the gapA promoter in strain WT Delta ptsH rendered the strain capable of growing on glucose, and deletion of bglF in strain SPH1 abolished the growth again, proving that bglF is responsible for glucose uptake in the suppressor strain. Simultaneous disruption of three glucokinase genes, glk (Cgl2185, NCgl2105), ppgK (Cgl1910, NCgl1835), and Cgl2647 (NCgl2558), in strain SPH1 resulted in no growth on glucose. Plasmid-mediated expression of any of the three genes in the triple-knockout mutant restored the growth on glucose. These results indicate that C. glutamicum ATCC 31833 has an additional non-PTS glucose uptake route consisting of the bglF-specified EII permease and native glucokinases.ArticleAPPLIED MICROBIOLOGY AND BIOTECHNOLOGY. 99(6):2741-2750 (2015)journal articl