Combination Therapy for Invasive Fungal Infections

The purpose of this review is to summarize and evaluate relevant literature on combination antifungal therapy for invasive fungal infections (IFIs). Cryptococcal meningitis has the largest body and highest quality in support of combination therapy with amphotericin B and flucytosine. More recent data in treatment of invasive aspergillosis suggest combination therapy with voriconazole and echinocandins may be effective in select patients. Quality studies are needed to define combination therapy in rare mold infections. Multiple strategies have been employed to optimize treatment of the growing incidence of IFIs. With exceptions as noted above, justification for the use of combination antifungal therapy is most often based on uncontrolled and/or underpowered studies, in vitro data, and case reports.     

The contribution of corals to reef structural complexity in Kāne‘ohe Bay

Coral Reefs - The structural complexity of coral reefs provides important ecosystem functions, such as wave attenuation for coastal protection, surfaces for coral growth, and habitat for other...     

Online auction marketplaces as a global pathway for aquatic invasive species

Hydrobiologia - The ornamental aquarium pet trade is a leading pathway for the introduction of aquatic invasive species. In addition to purchasing live organisms in stores, hobbyists are engaging...     

A Highlights from MBoC Selection: Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes

When clonal populations of human cells are exposed to apoptosis-inducing agents, some cells die and others survive. This fractional killing arises not from mutation but from preexisting, stochastic differences in the levels and activities of proteins regulating apoptosis. Here we examine the properties of cells that survive treatment with agonists of two distinct death receptors, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and anti-FasR antibodies. We find that “survivor” cells are highly resistant to a second ligand dose applied 1 d later. Resistance is reversible, resetting after several days of culture in the absence of death ligand. “Reset” cells appear identical to drug-naive cells with respect to death ligand sensitivity and gene expression profiles. TRAIL survivors are cross-resistant to activators of FasR and vice versa and exhibit an NF-κB–dependent inflammatory phenotype. Remarkably, reversible resistance is induced in the absence of cell death when caspase inhibitors are present and can be sustained for 1 wk or more, also without cell death, by periodic ligand exposure. Thus stochastic differences in cell state can have sustained consequences for sen­sitivity to prodeath ligands and acquisition of proinflammatory phenotypes. The important role played by periodicity in TRAIL exposure for induction of opposing apoptosis and survival mechanisms has implications for the design of optimal therapeutic agents and protocols.     

Application of an optimized marker amplification protocol in immunohistochemistry — a valuable tool for visualizing antigenic sites of low signal strength or sparse distribution

Amplification of immunohistochemical markers received considerable attention during the 1980s and 1990s. The amplification approach was largely abandoned following the development of antigen retrieval and reporter amplification techniques, because the latter were incorporated more easily into high throughput automated procedures in industrial and diagnostic laboratories. There remain, however, a number of instances where marker amplification still has much to offer. Consequently, we examined experimentally the utility of an optimized marker amplification technique in diagnostically relevant tissue where either the original signal strength was low or positive sites were visible, but sparsely distributed. Marker amplification in the former case not only improved the visibility of existing positive sites, but also revealed additional sites that previously were undetectable. In the latter case, positive sites were rendered more intense and therefore more easily seen during low magnification examination of large areas of tissue.     

Isaac Lea's Palaeosauropus (= “Sauropus”) primaevus: A Review of His Discovery

In 1849, Isaac Lea named Sauropus primaevus for footprints from Mount Carbon, Pennsylvania, USA, then the oldest fossil vertebrate footprints reported. In 1902, O. P. Hay constructed a new ichnogenus Palaeosauropus for this ichnospecies. Palaeosauropus has been one of the most frequently reported Mississippian footprint ichnogenera in North America and remains a valid ichnotaxon. The holotype of Palaeosauropus (= “Sauropus”) primaevus (referred to as P. primaevus), consisting of a single manus/pes pair, is described and illustrated in Lea (1853) Lea, I. 1853. On the fossil foot-marks in the Red Sandstones of Pottsville, Schuylkill County, Penna. Transactions of the American Philosophical Society, 10(new series): 307–315.  [Google Scholar] and is housed at the Academy of Natural Sciences in Philadelphia, Pennsylvania (ANS9752). Lea's large specimen of P. primaevus (approximately 86 cm by 53 cm), that included a trackway of six manus/pes pairs, described and illustrated in 1853 and 1855, was a combination of ANS9752 and a second specimen represented by a plaster cast housed at the National Museum of Natural History (USNM487148). Historical documents and examination of the Mauch Chunk Formation at Mount Carbon, Pennsylvania, enabled the identification of Lea's tracksite, originally reported to be a few hundred feet (about 75 m) from the former Mount Carbon Hotel. Our forensic evidence indicates the type locality for P. primaevus is approximately 90 m south from the southwest corner of Centre and Main Streets in Mount Carbon, Pennsylvania, with geographical coordinates of N 40° 40' 25.7”, W 76° 11' 14.9”. The type locality is within the middle member of the Mauch Chunk Formation, a fluvial sequence of late Mississippian (Visean) Age.     

Tetrapod Footprint Biostratigraphy and Biochronology

Tetrapod footprints have a fossil record in rocks of Devonian-Neogene age. Three principal factors limit their use in biostratigraphy and biochronology (palichnostratigraphy): invalid ichnotaxa based on extramorphological variants, slow apparent evolutionary turnover rates and facies restrictions. The ichnotaxonomy of tetrapod footprints has generally been oversplit, largely due to a failure to appreciate extramorphological variation. Thus, many tetrapod footprint ichnogenera and most ichnospecies are useless phantom taxa that confound biostratigraphic correlation and biochronological subdivision. Tracks rarely allow identification of a genus or species known from the body fossil record. Indeed, almost all tetrapod footprint ichnogenera are equivalent to a family or a higher taxon (order, superorder, etc.) based on body fossils. This means that ichnogenera necessarily have much longer temporal ranges and therefore slower apparent evolutionary turnover rates than do body fossil genera. Because of this, footprints cannot provide as refined a subdivision of geological time as do body fossils. The tetrapod footprint record is much more facies controlled than the tetrapod body fossil record. The relatively narrow facies window for track preservation, and the fact that tracks are almost never transported, redeposited or reworked, limits the facies that can be correlated with any track-based biostratigraphy.

A Devonian-Neogene global biochronology based on tetrapod footprints generally resolves geologic time about 20 to 50 percent as well as does the tetrapod body fossil record. The following globally recognizable time intervals can be based on the track record: (1) Late Devonian; (2) Mississippian; (3) Early-Middle Pennsylvanian; (4) Late Pennsylvanian; (5) Early Permian; (6) Late Permian; (7) Early-Middle Triassic; (8) late Middle Triassic; (9) Late Triassic; (10) Early Jurassic; (11) Middle-Late Jurassic; (12) Early Cretaceous; (13) Late Cretaceous; (14) Paleogene; (15) Neogene. Tetrapod footprints are most valuable in establishing biostratigraphic datum points, and this is their primary value to understanding the stratigraphic (temporal) dimension of tetrapod evolution.