Isolation of a peptide inhibitor of human rhinovirus

Cell culture-based transdominant genetic techniques provide new methods for discovering peptide/RNA modulators of cellular pathways. We applied this technology to isolate a peptide inhibitor of human rhinovirus. A green fluorescent protein (GFP)-scaffolded library of cDNA fragments was expressed in HeLa cells from a retroviral vector and screened for inhibitors of rhinovirus-mediated cell killing. A DNA clone, I421, increased cell survival in an HRV14 challenge assay from less than 0.5% to greater than 60%. It encodes a 53-amino-acid C-terminal extension of the GFP scaffold. Particular subclones of Hela cells expressing I421 (exemplified by I421dp3) show a delay in virus production and a 50-fold decrease in viral RNA levels at 6-8 h postinfection. HRV2, HRV14, and HRV16 show a dramatic decrease in plaque-forming ability on I421dp3 while Coxsackievirus B3 showed a small reduction. Levels of ICAM-1, the receptor for the main rhinovirus serotype, are not altered in I421dp3.     

Extension of the statistical theory of resonating valence bonds to hyperelectronic metals

The statistical treatment of resonating covalent bonds in metals, previously applied to hypoelectronic metals, is extended to hyperelectronic metals and to metals with two kinds of bonds. The theory leads to half-integral values of the valence for hyperelectronic metallic elements.     

A revised set of values of single-bond radii derived from the observed interatomic distances in metals by correction for bond number and resonance energy

An earlier discussion [Pauling, L. (1947) J. Am. Chem. Soc. 69, 542] of observed bond lengths in elemental metals with correction for bond number and resonance energy led to a set of single-bond metallic radii with values usually somewhat less than the corresponding values obtained from molecules and complex ions. A theory of resonating covalent bonds has now been developed that permits calculation of the number of resonance structures per atom and of the effective resonance energy per bond. With this refined method of correcting the observed bond lengths for the effect of resonance energy, a new set of single-bond covalent radii, in better agreement with values from molecules and complex ions, has been constructed.     

Syphilis Among U.S.-Bound Refugees, 2009–2013

U.S. immigration regulations require clinical and serologic screening for syphilis for all U.S.-bound refugees 15 years of age and older. We reviewed syphilis screening results for all U.S.-bound refugees from January 1, 2009 through December 31, 2013. We calculated age-adjusted prevalence by region and nationality and assessed factors associated with syphilis seropositivity using multivariable log binomial regression models. Among 233,446 refugees, we identified 874 syphilis cases (373 cases per 100,000 refugees). The highest overall age-adjusted prevalence rates of syphilis seropositivity were observed among refugees from Africa (1340 cases per 100,000), followed by East Asia and the Pacific (397 cases per 100,000). In most regions, male sex, increasing age, and living in non-refugee camp settings were associated with syphilis seropositivity. Future analysis of test results, stage of infection, and treatment delivery overseas is warranted in order to determine the extent of transmission risk and benefits of the screening program.     

What's wrong with our cancer models?

Oncology, as a therapeutic area, is characterized by a desperate medical need for new drugs; the use of drugs that kill cells and which are consequently often toxic; and rates of failure in expensive Phase III trials that eclipse many other disease areas. The poor performance of most investigational cancer drugs implies that the standard preclinical disease models are faulty or, at least, improperly used. Some studies, however, support the view that cancer models can be highly effective, but only when selected and interpreted with care.     

Human potassium channel genes: Molecular cloning and functional expression

Complementary DNAs representing three voltage-gated K⁺ channels from humans (HuKI, HuKII, and HuKIV) were isolated, their nucleotide sequences determined, and their functional products examined electrophysiologically. The three human K⁺ channels are closely related to the Shaker gene of Drosophila and possess several canonical structural features including multiple hydrophobic segments which are potentially membrane spanning, a positively charged S4 segment which may be the voltage sensor, and a leucine heptad repeat which may be involved in channel gating. Members of the human gene family have specific, highly conserved homologs in rodents, suggesting that the individual members arose prior to the mammalian radiation. The degree of homology indicates that these are among the most highly conserved proteins known. The three human channels expressed in Xenopus oocytes vary in voltage dependence, kinetics, and sensitivity to pharmacological blockers of K⁺ channels. HuKII is a rapidly inactivating channel; HuKI and HuKIV are noninactivating. Also, although all three channels are sensitive to the K⁺ channel blocker, 4-aminopyridine, only HuKI has tetraethylammonium sensitivity; only HuKIV has charybdotoxin sensitivity. Differences are observed between the pharmacological sensitivities of human channels and the reported sensitivities of their rat homology.     

Isolation of a diverged homeobox gene, M0X1, from the BRCA1 region on 17q21 by solution hybrid capture

Using the technique of solution hybridization coupled with magneticbead capture, we have isolated a novel homeobox-containing genefrom the BRCA1 region of 17q21. This gene is the human homologueof the mouse Mox1 gene previously localized to a syntenic regionof mouse chromosome 11. Multiple overlapping cDNAs of humanM0X1 were Identified using both a cosmid and a P1 genomic clonecontaining the microsatellite markers D17S750 and D17S858 whichmap within the BRCA1 region defined by D17S776 and D17S78. M0X1expression was observed In a variety of normal tissues examined,Including breast and ovary. Given that the gene contains a homeoboxdomain and has the potential to regulate growth and differentiation,M0X1 represents an attractive candidate for the BRCA1 gene.This possibility was Investigated in a series of BRCA1 kindredsand primary sporadic breast tumors. No evidence for mutationwas found In the coding sequence, making It unlikely that M0X1Is the BRCA1 gene. However, the widespread expression of M0X1in non-embryonal tissues suggests a role In normal cell biologywhich warrants further study.