Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs).

Background: Main-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs.

High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming.

Macrophages are plastic and, in response to different local stimuli, can polarize toward multi-dimensional spectrum of phenotypes, including the pro-inflammatory M1-like and the anti-inflammatory M2-like states. Using a high-throughput phenotypic screen in a library of ~4000 FDA-approved drugs, bioactive compounds and natural products, we find ~300 compounds that potently activate primary human macrophages toward either M1-like or M2-like state, of which ~30 are capable of reprogramming M1-like macrophages toward M2-like state and another ~20 for the reverse repolarization. Transcriptional analyses of macrophages treated with 34 non-redundant compounds identify both shared and unique targets and pathways through which the tested compounds modulate macrophage activation.

MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme.

ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these outputs are regulated to balance the cellular requirement for energy and heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples mitochondrial respiration to switch ATP synthesis to thermogenesis in response to heme.

1,3,5-Triazine as a modular scaffold for covalent inhibitors with streamlined target identification.

Small-molecule inhibitors can accelerate the functional annotation and validate the therapeutic potential of proteins implicated in disease. Phenotypic screens provide an effective platform to identify such pharmacological agents but are often hindered by challenges associated with target identification. For many protein targets, these bottlenecks can be overcome by incorporating electrophiles into small molecules to covalently trap interactions in vivo and by employing bioorthogonal handles to enrich the protein targets directly from a complex proteome.

Poverty alleviation and environmental restoration using the clean development mechanism: A case study from Humbo, Ethiopia.

Poverty, hunger and demand for agricultural land have driven local communities to overexploit forest resources throughout Ethiopia. Forests surrounding the township of Humbo were largely destroyed by the late 1960s. In 2004, World Vision Australia and World Vision Ethiopia identified forestry-based carbon sequestration as a potential means to stimulate community development while engaging in environmental restoration.

Roads from vaccines to therapies.

Over the past decade, we have demonstrated that various recombinant fragments of botulinum neurotoxin are highly immunogenic, stimulating notable levels of protective antibodies in mice, guinea pigs, and nonhuman primates. One of the fragments evaluated, the fragment C, is a potential next-generation vaccine candidate to replace the current pentavalent botulinum toxoid vaccine. Synthetic genes encoding the carboxyl-terminal regions (approximately 50 kDa) of toxin types A, B, C1, E, and F were expressed in Pichia pastoris, and manufacturing processes were developed for producing highly purified vaccines.