Contribution of Clinically Derived Mutations in ERG11 to Azole Resistance in Candida albicans

In Candida albicans, the ERG11 gene encodes lanosterol demethylase, the target of the azole antifungals. Mutations in ERG11 that result in an amino acid substitution alter the abilities of the azoles to bind to and inhibit Erg11, resulting in resistance. Although ERG11 mutations have been observed in clinical isolates, the specific contributions of individual ERG11 mutations to azole resistance in C. albicans have not been widely explored. We sequenced ERG11 in 63 fluconazole (FLC)-resistant clinical isolates. Fifty-five isolates carried at least one mutation in ERG11, and we observed 26 distinct positions in which amino acid substitutions occurred. We mapped the 26 distinct variant positions in these alleles to four regions in the predicted structure for Erg11, including its predicted catalytic site, extended fungus-specific external loop, proximal surface, and proximal surface-to-heme region. In total, 31 distinct ERG11 alleles were recovered, with 10 ERG11 alleles containing a single amino acid substitution. We then characterized 19 distinct ERG11 alleles by introducing them into the wild-type azole-susceptible C. albicans SC5314 strain and testing them for susceptibilities to FLC, itraconazole (ITC), and voriconazole (VRC). The strains that were homozygous for the single amino acid substitutions Y132F, K143R, F145L, S405F, D446E, G448E, F449V, G450E, and G464S had a ≥4-fold increase in FLC MIC. The strains that were homozygous for several double amino acid substitutions had decreased azole susceptibilities beyond those conferred by any single amino acid substitution. These findings indicate that mutations in ERG11 are prevalent among azole-resistant clinical isolates and that most mutations result in appreciable changes in FLC and VRC susceptibilities.     

Metal phthalocyanine organic thin-film transistors: changes in electrical performance and stability in response to temperature and environment

Metal phthalocyanines (MPcs) are a widely studied class of materials that are frequently used in organic thin-film transistors (OTFTs), organic photovoltaics (OPVs) and organic light emitting diodes (OLEDs). The stability of these devices and the materials used in their fabrication is important to realize their widespread adoption. Seven P-type MPcs: zinc (ZnPc), magnesium (MgPc), aluminum (AlClPc), iron (FePc), cobalt (CoPc), and titanium (TiOPc) were investigated as the semiconductors in OTFTs under varying temperatures (25 °C to 150 °C) and environmental conditions (air and vacuum, P < 0.1 Pa). Devices using the divalent MPcs (except MgPc) showed significant shifts in threshold voltage and field-effect mobility with rising temperature in both air and vacuum. AlClPc and TiOPc, on the other hand, had more stable electrical properties, making them useful for applications requiring consistent performance. Distinct variations in film morphology as determined by atomic force microscopy may explain the different thermal response between the two groups of MPcs, while thermal gravimetric analysis in air and nitrogen (N₂) provides additional insight into their susceptibility to oxidation at elevated temperature. To demonstrate proof-of-concept thermal sensing under realistic operating conditions, current changes were monitored in response to temperature stimuli using two more sensitive divalent MPcs. This comparative study of the effect of central atom inclusion in MPcs, the resulting material stability and thin-film characteristics will facilitate design of future sensors and other OTFT applications.

A series of metal phthalocyanine based organic thin film transistors were evaluated and their responses to changes in temperature and environmental was determined: the choice of central atom makes a difference.     

Religion as a means to assure paternity

The sacred texts of five world religions (Buddhism, Christianity, Hinduism, Islam, and Judaism) use similar belief systems to set limits on sexual behavior. We propose that this similarity is a shared cultural solution to a biological problem: namely male uncertainty over the paternity of offspring. Furthermore, we propose the hypothesis that religious practices that more strongly regulate female sexuality should be more successful at promoting paternity certainty. Using genetic data on 1,706 father-son pairs, we tested this hypothesis in a traditional African population in which multiple religions (Islam, Christianity, and indigenous) coexist in the same families and villages. We show that the indigenous religion enables males to achieve a significantly (P = 0.019) lower probability of cuckoldry (1.3% versus 2.9%) by enforcing the honest signaling of menstruation, but that all three religions share tenets aimed at the avoidance of extrapair copulation. Our findings provide evidence for high paternity certainty in a traditional African population, and they shed light on the reproductive agendas that underlie religious patriarchy.     

'Not another UTI ... '

Malaria includes a global disease burden with approximately 300-500 million cases worldwide annually. Varied symptomatology creates a diagnostic challenge. This is a case report of a stroke rehabilitation facility resident who developed Plasmodium ovale infection, several months post-exposure. Physicians should maintain a broad list of differential diagnoses, thinking beyond the range of common diagnoses.