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1.
Cell Stress Chaperones ; 29(2): 312-325, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38490439

ABSTRACT

Type 1 diabetes (T1D) is characterized by lymphocyte infiltration into the pancreatic islets of Langerhans, leading to the destruction of insulin-producing beta cells and uncontrolled hyperglycemia. In the nonobese diabetic (NOD) murine model of T1D, the onset of this infiltration starts several weeks before glucose dysregulation and overt diabetes. Recruitment of immune cells to the islets is mediated by several chemotactic cytokines, including CXCL10, while other cytokines, including SDF-1α, can confer protective effects. Global gene expression studies of the pancreas from prediabetic NOD mice and single-cell sequence analysis of human islets from prediabetic, autoantibody-positive patients showed an increased expression of metallothionein (MT), a small molecular weight, cysteine-rich metal-binding stress response protein. We have shown that beta cells can release MT into the extracellular environment, which can subsequently enhance the chemotactic response of Th1 cells to CXCL10 and interfere with the chemotactic response of Th2 cells to SDF-1α. These effects can be blocked in vitro with a monoclonal anti-MT antibody, clone UC1MT. When administered to NOD mice before the onset of diabetes, UC1MT significantly reduces the development of T1D. Manipulation of extracellular MT may be an important approach to preserving beta cell function and preventing the development of T1D.


Subject(s)
Diabetes Mellitus, Type 1 , Prediabetic State , Humans , Mice , Animals , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/prevention & control , Mice, Inbred NOD , Metallothionein/genetics , Metallothionein/metabolism , Chemokine CXCL12
2.
Appl Environ Microbiol ; 75(12): 4089-92, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19376913

ABSTRACT

Listeria monocytogenes is a food-borne pathogen capable of forming biofilms and persisting in food processing environments for extended periods of time, thereby potentially contaminating foods. The efficacy of octenidine hydrochloride (OH) for inactivating planktonic cells and preformed biofilms of L. monocytogenes was investigated at 37, 21, 8, and 4 degrees C in the presence and absence of organic matter (rehydrated nonfat dry milk). OH rapidly killed planktonic cells and biofilms of L. monocytogenes at all four temperatures. Moreover, OH was equally effective in killing L. monocytogenes biofilms on polystyrene and stainless steel matrices in the presence and absence of organic matter. The results underscore OH's ability to prevent establishment of L. monocytogenes biofilms by rapidly killing planktonic cells and to eliminate preformed biofilms, thus suggesting that it could be used as a disinfectant to prevent L. monocytogenes from persisting in food processing environments.


Subject(s)
Biofilms/drug effects , Disinfectants/pharmacology , Listeria monocytogenes/drug effects , Pyridines/pharmacology , Imines , Microbial Viability/drug effects , Temperature
3.
Theor Appl Genet ; 117(8): 1335-44, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18769903

ABSTRACT

The construction of large-scale databases of molecular profiles of plant varieties for variety identification and diversity analyses is of considerable interest. When varieties of an allogamous species such as oilseed rape are analysed and described using molecular markers such as microsatellites, care is needed to represent the variety in a meaningful yet useful way. It is possible to characterise such heterogeneous genotypes by analysing bulked samples comprising more than one individual seed or plant, but this approach may result in complex microsatellite profiles. Intuitively it would be reasonable to represent a variety by the common 'major alleles' in a profile, but how to define these 'major alleles' remains problematic. This paper describes methods of analysing DNA microsatellite data that will allow independent and objective data production at a number of laboratories. Methods for establishing allele scoring rules (thresholding) are described and the effect of these rules on the utility of the data is discussed.


Subject(s)
Crops, Agricultural/genetics , DNA, Plant/analysis , Databases, Genetic , Laboratories/standards , Microsatellite Repeats , Alleles , Genetic Markers , Genotype , Reference Standards , Reproducibility of Results , Sequence Analysis, DNA
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