The Fanconi anemia pathway is required for repair of DNA interstrand cross-links (ICL). Fanconi anemia pathway–deficient cells are hypersensitive to DNA ICL–inducing drugs such as cisplatin. Conversely, hyperactivation of the Fanconi anemia pathway is a mechanism that may underlie cellular resistance to DNA ICL agents. Modulating FANCD2 monoubiquitination, a key step in the Fanconi anemia pathw...

The volume-sensitive chloride current (ICl,swell) is found in the mammalian myocardium and is activated by osmotic swelling. The goal of this study was to examine the importance of the tyrosine kinases focal adhesion kinase (FAK) and Src kinase in cardiac ICl,swell regulation. Neonatal rat ventricular myocytes were cultured on collagen membranes and infected with adenovirus expressing beta-gala...

Whole cell patch clamp recordings were made from cultured myenteric neurons taken from murine proximal colon. The micropipette contained Cs to remove K currents. Depolarization elicited a slowly activating time-dependent outward current (Itdo), whereas, repolarization was followed by a slowly deactivating tail current (Itail). Itdo and Itail were present in about 70% of neurons. We identified t...

Isocitrate lyase, ICL (EC 4.1.3.1), an enzyme that cleaves isocitrate into succinate, and glyoxylate appears to play a pivotal role in the detoxification of aluminum (Al) in Pseudomonas fluorescens. Here, we present evidence that the 4-fold increase in ICL activity observed in Al-stressed cells is due to the overexpression of this enzyme. Blue-Native-PAGE, Western blotting, and spectrophotometr...

Post-translational modification of protein cysteine residues is emerging as an important regulatory and signaling mechanism. We have identified numerous putative targets of redox regulation in the unicellular green alga Chlamydomonas reinhardtii. One enzyme, isocitrate lyase (ICL), was identified both as a putative thioredoxin target and as an S-thiolated protein in vivo. ICL is a key enzyme of...

Mitomycin C (MC), a commonly used anticancer drug, induces DNA damage via DNA alkylation. Decarbamoyl mitomycin C (DMC), another mitomycin lacking the carbamate at C10, generates similar lesions as MC. Interstrand cross-links (ICLs) are believed to be the lesions primarily responsible for the cytotoxicity of MC and DMC. The major ICL generated by MC (α-ICL) has a trans stereochemistry at the gu...

DNA interstrand cross-links (ICLs) are repaired in S phase by a complex, multistep mechanism involving translesion DNA polymerases. After replication forks collide with an ICL, the leading strand approaches to within one nucleotide of the ICL ("approach"), a nucleotide is inserted across from the unhooked lesion ("insertion"), and the leading strand is extended beyond the lesion ("extension"). ...

Translocation of microbial products has been described in chronic human immunodeficiency virus (HIV) infection and correlates with activation of the immune system. We investigated the potential translocation of microbial products in idiopathic CD4 lymphocytopenia (ICL), a rare disorder characterized by low CD4 T cell counts in the absence of HIV infection. Plasma lipopolysaccharide (LPS) levels...

Idiopathic CD4 T-lymphocytopenia (ICL) is a rare immunodeficiency characterized by low CD4 T-lymphocyte count, which usually manifests with opportunistic infections. Nocardia as an opportunistic pathogen infecting patients with this condition has rarely been reported. Here, we describe the case of a 46-year-old male who presented with lung mass and respiratory and systemic symptoms and was even...

We introduce a propositional logic ICL, which adds to intuitionistic logic elements of classical reasoning without collapsing it into classical logic. This logic includes a new constant for false, which augments false in intuitionistic logic and in minimal logic. We define Kripke models for ICL and show how they translate to several other forms of semantics. We define a sequent calculus and pro...