in an attempt to assess objectively the integrity of the auditory pathways in 30 patients with definite multiple sclerosis (ms), an audiometric evaluation was performed and auditory brainstem responses (abrs) were obtained. stressing the auditory system by increasing the stimulation rate showed some enhancement in the identification of ms. 24 (ro%) patients had an abnormal abr along with clinic...

BACKGROUND Isoflavonoids are of interest owing to their appearance in metabolic pathways of isoflavones, and their estrogenic and other physiological properties, making them promising lead compounds for drug design. RESULTS The reduction of isoflavones by various hydride reagents occurs by a 1,4-pathway in contrast to ordinary beta-alkoxy-alpha,beta-unsaturated ketones. Isoflavan-4-ones, cis-...

Peroxisomes are unique among the organelles of the endomembrane system. Unlike other organelles that derive most if not all of their proteins from the ER (endoplasmic reticulum), peroxisomes contain dedicated machineries for import of matrix proteins and insertion of membrane proteins. However, peroxisomes are also able to import a subset of their membrane proteins from the ER. One aspect of pe...

Mitochondria import hundreds of different precursor proteins from the cytosol. More than 50% of mitochondrial proteins do not use the classical import pathway that is guided by amino-terminal presequences, but instead contain different types of internal targeting signals. Recent studies have revealed an unexpected complexity of the mitochondrial protein import machinery and have led to the disc...

wnloaded s perspective places the report by Villani et al. that appears in this issue of the journal (beginning ge 1222) in the context of recent work showing an intersection between two important developl pathways implicated in oncogenesis: the hedgehog and insulin-like growth factor (IGF) pathVillani et al. define a key role for the IGF regulatory protein Igfbp2 in a genetic model of basal rc...

BACKGROUND Genotype x environment interaction (G x E) arises when genes influence sensitivity to the environment. G x E is easily recognized in experimental organisms that permit randomization of genotypes over fixed environmental treatments. Genotype-environment correlation (rGE) arises when genetic effects create or evoke exposure to environmental differences. Simultaneous analysis of G x E a...

Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin...

TWEAK, a recently identified member of the TNF family, is expressed on IFN-gamma-stimulated monocytes and induces cell death in certain tumor cell lines. In this study, we characterized the TWEAK-induced cell death in several tumor cell lines that exhibited distinct features. Although the TWEAK-induced cell death in Kym-1 cells was indirectly mediated by TNF-alpha and was inhibited by cyclohexi...

Experimental observations suggest that proteins follow different folding pathways under different environmental conditions. We perform molecular dynamics simulations of a model of the c-Crk SH3 domain over a broad range of temperatures, and identify distinct pathways in the folding transition. We determine the kinetic partition temperature-the temperature for which the c-Crk SH3 domain undergoe...

In order to eliminate cells that are redundant, damaged, or infected, metazoan organisms have evolved the cell suicide mechanism termed apoptosis (Kerr et al. 1972). This genetic program is vital for normal development, for maintenance of tissue homeostasis, and for an effective immune system. Not surprisingly therefore, its disturbance is implicated in numerous pathological conditions, ranging...