Persistent infection with one or more highly oncogenic human papillomaviruses (HPVs) or high-risk-HPV (HR-HPV) is necessary but not a sufficient aetiological agent for the development of cervical neoplasia. A number of viral, host, environmental and behavioural factors are suggested to be associated with the progression of cervical disorder. This study aimed to evaluate the impact of environmental and behavioural cofactors on the development of cervical disorders in HR-HPV-infected women in Serbia. A total of 541 women have been tested by PCR for the presence of HPV on the cervix. HPV genotypes were determined by direct DNA sequencing. Women identified as HR-HPV-positive were further classified into four subgroups according to their cytological status. All relevant information about demographical and behavioural factors was obtained by interviewer-based questionnaire. A number of analytical and descriptive statistical methods were used for processing the data. The cofactors found to be of significance for the progression of cervical disease were older age, body mass index >25, lower educational level, long-term smoking, previous genital infections and cervical interventions. On the other hand, condom use was found to have a protective role. Information about these cofactors might be very important for the development of more efficient cancer prevention programmes and promotion of anti-HPV vaccination.

Two red rice accessions from Arkansas have been found to be resistant to the labeled rate of imazethapyr, which is used to control red rice in ClearfieldTM rice. Full-length amplification of the acetolactate synthase (ALS) gene in imazethapyr-resistant red rice revealed a coding sequence of 1,935 base pairs, which is the same as that of the cultivated rice. Coding sequences were generated from four red rice accessions collected from different geographical regions in Arkansas, consisting of accessions that were either resistant or susceptible to imazethapyr. Nucleotide sequence alignments identified six base polymorphisms, three of which resulted in amino acid substitutions in the ALS gene. One amino acid substitution, Gly654Glu, involves a residue required for imazethapyr binding to the ALS. The other substitution, Val669Met, implies conformational changes in the ALS structure that enhances binding of thiamine diphosphate, an ALS cofactor. These novel amino acid substitutions first reported for ALS-resistant red rice accessions support the hypothesis that ALS-resistant red rice can evolve with sustained herbicide selection pressure. Thus, it behooves growers to integrate the Cleafield rice technology with other tools to achieve a successful, long-term weed management program.

The management of ethylene glycol poisoning is reviewed, with a focus on the use of the new antidote fomepizole. Ethylene glycol is a widely used industrial agent that is also easily obtained commercially, usually as radiator antifreeze. Ingestion of as little as 30 to 60 mL can result in death or serious permanent disability. Traditional management of poisoning includes the use of ethanol, with or without hemodialysis. Activated charcoal is not indicated, and gastric lavage may be beneficial only in the first hour after ingestion. Cofactors such as pyridoxine and thiamine may be beneficial in patients deficient in these vitamins. A new antidote, fomepizole, has recently been approved for use in Canada. Like ethanol, it is a competitive inhibitor of alcohol dehydrogenase. Potential benefits of fomepizole include its ease of administration and lack of serious adverse effects. Fomepizole may be recommended over ethanol in situations in which avoidance of ethanol-induced side effects is imperative or when ethanol is not readily available. Further studies are required to verify its comparative efficacy and cost-effectiveness compared to ethanol.

Proteins often require cofactors to perform their biological functions and must fold in the presence of their cognate ligands. Using circular dichroism spectroscopy, we investigated the effects of divalent metal binding upon the folding pathway of Escherichia coli RNase HI. This enzyme binds divalent metal in its active site, which is proximal to the folding core of RNase HI as defined by hydrogen/deuterium exchange studies. Metal binding increases the apparent stability of native RNase HI chiefly by reducing the unfolding rate. As with the apo-form of the protein, refolding from high denaturant concentrations in the presence of Mg2+ follows three-state kinetics: formation of a rapid burst phase followed by measurable single exponential kinetics. Therefore, the overall folding pathway of RNase HI is minimally perturbed by the presence of metal ions. Our results indicate that the metal cofactor enters the active site pocket only after the enzyme reaches its native fold, and therefore, divalent metal binding stabilizes the protein by decreasing its unfolding rate. Furthermore, the binding of the cofactor is dependent upon a carboxylate critical for activity (Asp10). A mutation in this residue (D10A) alters the folding kinetics in the absence of metal ions such that they are similar to those observed for the unaltered enzyme in the presence of metal.