Bioremediation is an important approach to waste reduction that relies on biological processes to break down a variety of pollutants. This is made possible by the vast metabolic diversity of the microbial world. To explore this diversity for the breakdown of plastic, we screened several dozen endophytic fungi for their ability to degrade the synthetic polymer polyester polyurethane (PUR). Several organisms demonstrated the ability to efficiently degrade PUR in both solid and liquid suspensions. Particularly robust activity was observed among several isolates in the genus Pestalotiopsis, although it was not a universal feature of this genus. Two Pestalotiopsis microspora isolates were uniquely able to grow on PUR as the sole carbon source under both aerobic and anaerobic conditions. Molecular characterization of this activity suggests that a serine hydrolase is responsible for degradation of PUR. The broad distribution of activity observed and the unprecedented case of anaerobic growth using PUR as the sole carbon source suggest that endophytes are a promising source of biodiversity from which to screen for metabolic properties useful for bioremediation.Tremendous increases in the manufacture and consumption of plastics over recent decades have led to numerous ecological and economic concerns. The persistence of synthetic polymers introduced into the environment by human industry poses a major threat to natural ecological systems. The low cost and ease of manufacture have increased global plastic demand more than 150-fold, with the production of 1.5 million tons in 1950 and 245 million tons as of 2006 (21). Despite recognition of the persistent pollution problems posed by plastic, global production is still increasing, with the largest increases expected in developing nations. The sheer volume of plastics produced each year presents a problem for waste disposal systems. The scale of this problem and the recalcitrance of some polymers to degradation necessitate investigation into effective methods for biodegradation of plastics. By gaining an understanding of the mechanisms of polymer degradation, a more efficient technique for the biodegradation of plastic waste can be achieved. To accomplish this goal, researchers need greater knowledge of how compounds are metabolized by existing organisms, an investigation of new organisms with bioremediation potential, and the characterization of novel metabolic capabilities.

Signaling via the Pyk2-Src-Cbl complex downstream of integrins contributes to the assembly, organization, and dynamics of podosomes, which are the transient adhesion complexes of highly motile cells such as osteoclasts and dendritic cells. We previously demonstrated that the GTPase dynamin is associated with podosomes, regulates actin flux in podosomes, and promotes bone resorption by osteoclasts. We report here that dynamin associates with Pyk2, independent of dynamin's GTPase activity, and reduces Pyk2 Y402 phosphorylation in a GTPase-dependent manner, leading to decreased Src binding to Pyk2. Overexpressing dynamin decreased the macrophage colony-stimulating factor-and adhesion-induced phosphorylation of Pyk2 in osteoclastlike cells, suggesting that dynamin is likely to regulate Src-Pyk2 binding downstream of integrins and growth factor receptors with important cellular consequences. Furthermore, catalytically active Src promotes dynamin-Pyk2 association, and mutating specific Src-phosphorylated tyrosine residues in dynamin blunts the dynamin-induced decrease in Pyk2 phosphorylation. Thus, since Src binds to Pyk2 through its interaction with phospho-Y402, our results suggest that Src activates a negative-feedback loop downstream of integrin engagement and other stimuli by promoting both the binding of dynamin to Pyk2-containing complexes and the dynamin-dependent decrease in Pyk2 Y402 phosphorylation, ultimately leading to the dissociation of Src from Pyk2.Podosomes are specialized transient actin-containing adhesion structures (11,14,37,60) that are found in highly motile cells, such as osteoclasts, macrophages, dendritic cells, transformed metastatic cells, and v-src-transformed cells (37, 43), where they are thought to play important roles in cellular migration and invasion (34). In resorbing osteoclasts on bone, podosomes are concentrated within the sealing zone, a beltlike actin-rich structure that is important for adhesion and which delineates the resorptive region of the cell known as the ruffled border. Unlike focal adhesions, which are relatively stable structures (11, 60), the assembly and disassembly of podosomes occurs within minutes (t 1/2 ϭ 2 to 4 min) and involves the recruitment and activation of integrins, signaling proteins and scaffolding proteins (11,14,35,47,60). However, the mechanisms of action of key signaling proteins involved in podosome assembly and disassembly are only partially understood.The focal adhesion kinase Pyk2 has been linked to the proliferation, migration, and activity of a variety of mesenchymal, epithelial, and hematopoietic cell types. Several groups, including our own, have reported the importance of Pyk2 in podosome belt organization, cell spreading, and bone-resorbing activity in osteoclasts (18,26,31,40,65,66). Pyk2 is recruited to activated ␤ 2 and ␤ 3 integrins (9, 20) at adhesion sites and is autophosphorylated at Y402 (17, 47, 50) via an intermolecular trans-acting mechanism (46). Although Pyk2 is partially activated by integrin-induced Ca 2ϩ signaling (20, 5...

Fluoropyrimidines constitute the backbone of chemotherapy regimens for gastrointestinal tumors, especially colorectal cancer (CRC). Comparison of oral and intravenous fluoropyrimidine treatments in patients with CRC has shown that hand-and-foot syndrome (HFS) (all grades) has the most frequently reported association with toxicity from capecitabine, an oral fluoropyrimidine. Present grading guidelines are generalized to patients belonging to all ethnicities. However, we noticed varying pattern and degree of manifestations of all grades of HFS in non-white patients as compared with white patients. This article presents the case of a 69-year-old African American man with a gastric adenocarcinoma status post gastrectomy who received 5-fluorouracil (5-FU) plus leucovorin for 5 days, to be followed by radiation plus capecitabine given 5 days per week for 5 weeks, and then 8 weeks of capecitabine monotherapy. Capecitabine was substituted because of severe toxicity with 5-FU after determining that the level of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in the metabolism of fluoropyrimidines, was within normal limits. He developed discoloration of his palms consistent with HFS, contrary to the pattern and degree of HFS reported in the current guidelines as proposed in the drug insert. This case suggests that the pattern of cutaneous manifestations related to fluoropyrimidines may vary in patients with different ethnic backgrounds, especially whites Versus non-whites. This finding becomes more important as our recent findings suggest that DPD deficiency may be more common among African Americans. This case also suggests that severe toxicity to infusional 5-FU might not be indicative of severe toxicity to oral fluoropyrimidine drugs.

The use of protocolised EMRTs may improve the quality of patient care in IS and other rare diseases.