A viscoelastic deadly fluid in carnivorous pitcher plants

Background : The carnivorous plants of the genus Nepenthes, widely distributed in the Asian tropics, rely mostly on nutrients derived from arthropods trapped in their pitcher-shaped leaves and digested by their enzymatic fluid. The genus exhibits a great diversity of prey and pitcher forms and its mechanism of trapping has long intrigued scientists. The slippery inner surfaces of the pitchers, which can be waxy or highly wettable, have so far been considered as the key trapping devices. However, the occurrence of species lacking such epidermal specializations but still effective at trapping insects suggests the possible implication of other mechanisms. Methodology/Principal Findings : Using a combination of insect bioassays, high-speed video and rheological measurements, we show that the digestive fluid of Nepenthes rafflesiana is highly viscoelastic and that this physical property is crucial for the retention of insects in its traps. Trapping efficiency is shown to remain strong even when the fluid is highly diluted by water, as long as the elastic relaxation time of the fluid is higher than the typical time scale of insect movements. Conclusions/Significance : This finding challenges the common classification of Nepenthes pitchers as simple passive traps and is of great adaptive significance for these tropical plants, which are often submitted to high rainfalls and variations in fluid concentration. The viscoelastic trap constitutes a cryptic but potentially widespread adaptation of Nepenthes species and could be a homologous trait shared through common ancestry with the sundew (Drosera) flypaper plants. Such large production of a highly viscoelastic biopolymer fluid in permanent pools is nevertheless unique in the plant kingdom and suggests novel applications for pest control

Identification of a Novel Topoisomerase Inhibitor Effective in Cells Overexpressing Drug Efflux Transporters

BACKGROUND:Natural product structures have high chemical diversity and are attractive as lead structures for discovery of new drugs. One of the disease areas where natural products are most frequently used as therapeutics is oncology. METHOD AND FINDINGS:A library of natural products (NCI Natural Product set) was screened for compounds that induce apoptosis of HCT116 colon carcinoma cells using an assay that measures an endogenous caspase-cleavage product. One of the apoptosis-inducing compounds identified in the screen was thaspine (taspine), an alkaloid from the South American tree Croton lechleri. The cortex of this tree is used for medicinal purposes by tribes in the Amazonas basin. Thaspine was found to induce conformational activation of the pro-apoptotic proteins Bak and Bax, mitochondrial cytochrome c release and mitochondrial membrane permeabilization in HCT116 cells. Analysis of the gene expression signature of thaspine-treated cells suggested that thaspine is a topoisomerase inhibitor. Inhibition of both topoisomerase I and II was observed using in vitro assays, and thaspine was found to have a reduced cytotoxic effect on a cell line with a mutated topoisomerase II enzyme. Interestingly, in contrast to the topoisomerase II inhibitors doxorubicin, etoposide and mitoxantrone, thaspine was cytotoxic to cell lines overexpressing the PgP or MRP drug efflux transporters. We finally show that thaspine induces wide-spread apoptosis in colon carcinoma multicellular spheroids and that apoptosis is induced in two xenograft mouse models in vivo. CONCLUSIONS:The alkaloid thaspine from the cortex of Croton lechleri is a dual topoisomerase inhibitor effective in cells overexpressing drug efflux transporters and induces wide-spread apoptosis in multicellular spheroids

Rab protein evolution and the history of the eukaryotic endomembrane system

Spectacular increases in the quantity of sequence data genome have facilitated major advances in eukaryotic comparative genomics. By exploiting homology with classical model organisms, this makes possible predictions of pathways and cellular functions currently impossible to address in intractable organisms. Echoing realization that core metabolic processes were established very early following evolution of life on earth, it is now emerging that many eukaryotic cellular features, including the endomembrane system, are ancient and organized around near-universal principles. Rab proteins are key mediators of vesicle transport and specificity, and via the presence of multiple paralogues, alterations in interaction specificity and modification of pathways, contribute greatly to the evolution of complexity of membrane transport. Understanding system-level contributions of Rab proteins to evolutionary history provides insight into the multiple processes sculpting cellular transport pathways and the exciting challenges that we face in delving further into the origins of membrane trafficking specificity

From primary care to the revolving door of hospital readmission: Relevance of Geoffrey Rose's call for a population strategy

The high-risk strategy in prevention has remained the preferred approach in health care. High-profile research predominantly emphasizes specific high-risk subgroups such as those who have extremely high cholesterol and super-utilizers of emergency departments. Dr. Geoffrey Rose's alternative population approach, though well established in principle, has failed to come to fruition in primary care research, aside from a few exceptions. The population approach extends intervention efforts to more moderate-risk people, attempting to shift the overall distribution in a positive direction, effecting change in more of the population. Despite requiring more initial investment due to the larger target group, the health-related gains and downstream cost savings through a population strategy may yield greater long-term cost-effectiveness than the high-risk strategy. We describe the example of extending prevention efforts from super-utilizers (e.g. those with ≥3 readmissions per year) to include those who readmit in moderate frequency (1–2 per year) in terms of potential hospital days and associated medical costs averted. Keywords: Population health, Patient readmission, Preventive healt

Antifungal and Herbicidal Potential of Piper Essential Oils from the Peruvian Amazonia

The chemical composition of essential oils (EOs) from ten Peruvian Piper species (Piper coruscans, Pc; P. tuberculatum, Pt; P. casapiense, Pcs; P. obliquum, Po; P. dumosum, Pd; P. anonifolium, Pa; P. reticulatum, Pr; P. soledadense, Ps; P. sancti-felicis, Psf and P. mituense, Pm) has been studied, along with their antifungal and phytotoxic activities. These EOs contained β-bisabolene/nerolidol (Pc), β-bisabolene/δ-cadinene/caryophyllene (Pt), caryophyllene oxide (Pcs), bicyclogermacrene/10-epi-Elemol (Po), bicyclogermacrene/germacrene-D/apiol (Pd), caryophyllene/germacrene-D (Pa), germacrene-D (Pr), limonene/apiol (Ps), apiol (Psf), and apiol/bicyclogermacrene (Pm) as major components, and some are described here for the first time (Ps, Pcs, Pm). A composition-based dendrogram of these Piper species showed four major groups (G1: Pc and Pt, G2: Pcs, Po, Pd, Pa, and Pr, G3: Ps, and G4: Psf and Pm). The spore germination effects (Aspergillus niger, Botrytis cinerea, and Alternaria alternate) and phytotoxicity (Lolium perenne and Lactuca sativa) of these EOs were studied. Most of these Piper essential oils showed important activity against phytopathogenic fungi (except G1), especially against B. cinerea. Similarly, most of the essential oils were phytotoxic against L. perenne (except G1), with P. sancti-felicis (G4), P. casapiense (G2), and P. reticulatum (G2) being the most effective. Caryophyllene oxide, β-caryophyllene, β-pinene, limonene, α-humulene, and apiol were evaluated against B. cinerea, with the most effective compounds being β-pinene, apiol, and limonene. This work demonstrates the species-dependent potential of essential oils from Peruvian Piper species as fungicidal and herbicidal agents

Outcomes of an integrated practice unit for vulnerable emergency department patients

Abstract Background An integrated practice unit (IPU) that provides a multidisciplinary approach to patient care, typically involving a primary care provider, registered nurse, social worker, and pharmacist has been shown to reduce healthcare utilization among high-cost super-utilizer (SU) patients or multi-visit patients (MVP). However, less is known about differences in the impact of these interventions on insured vs. uninsured SU patients and super high frequency SUs ( $$\ge$$ 8 ED visits per 6 months) vs. high frequency SUs (4–7 ED visits per 6 months). Methods We assessed the percent reduction in ED visits, ED cost, hospitalizations, hospital days, and hospitalization costs following implementation of an IPU for SUs located in an academic tertiary care facility. We compared outcomes for publicly insured with uninsured patients, and super high frequency SUs with high frequency SUs 6 months before vs. 6 months after enrollment in the IPU. Results There was an overall 25% reduction in hospitalizations (p < 0.001), and 23% reduction in hospital days (p = 0.0045), when comparing 6 months before vs. 6 months after enrollment in the program. There was a 26% reduction in average total direct hospitalization costs per patient (p = 0.002). Further analysis revealed a greater reduction in health care utilization for uninsured SU patients compared with publicly insured patients. The program reduced hospitalizations for super high frequency SUs. However, there was no statistically significant impact on overall health care utilization of super high frequency SUs when compared with high frequency SUs. Conclusions Our study supports existing evidence that dedicated IPUs for SUs can achieve significant reductions in acute care utilization, particularly for uninsured and high frequency SU patients. Trial Registration IRB201500212. Retrospectively registered