Chemical warfare between leafcutter ant symbionts and a co-evolved pathogen

Acromyrmex leafcutter ants form a mutually beneficial symbiosis with the fungus Leucoagaricus gongylophorus and with Pseudonocardia bacteria. Both are vertically transmitted and actively maintained by the ants. The fungus garden is manured with freshly cut leaves and provides the sole food for the ant larvae, while Pseudonocardia cultures are reared on the ant-cuticle and make antifungal metabolites to help protect the cultivar against disease. If left unchecked, specialized parasitic Escovopsis fungi can overrun the fungus-garden and lead to colony collapse. We report that Escovopsis upregulates the production of two specialized metabolites when it infects the cultivar. These compounds inhibit Pseudonocardia and one, shearinine D, also reduces worker behavioral defences and is ultimately lethal when it accumulates in ant tissues. Our results are consistent with an active evolutionary arms race between Pseudonocardia and Escovopsis, which modifies both bacterial and behavioral defences such that colony collapse is unavoidable once Escovopsis infections escalate

Software for administering the National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events: Usability study

Background: The US National Cancer Institute (NCI) developed software to gather symptomatic adverse events directly from patients participating in clinical trials. The software administers surveys to patients using items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) through Web-based or automated telephone interfaces and facilitates the management of survey administration and the resultant data by professionals (clinicians and research associates). Objective: The purpose of this study was to iteratively evaluate and improve the usability of the PRO-CTCAE software. Methods: Heuristic evaluation of the software functionality was followed by semiscripted, think-aloud protocols in two consecutive rounds of usability testing among patients with cancer, clinicians, and research associates at 3 cancer centers. We conducted testing with patients both in clinics and at home (remotely) for both Web-based and telephone interfaces. Furthermore, we refined the software between rounds and retested. Results: Heuristic evaluation identified deviations from the best practices across 10 standardized categories, which informed initial software improvement. Subsequently, we conducted user-based testing among 169 patients and 47 professionals. Software modifications between rounds addressed identified issues, including difficulty using radio buttons, absence of survey progress indicators, and login problems (for patients) as well as scheduling of patient surveys (for professionals). The initial System Usability Scale (SUS) score for the patient Web-based interface was 86 and 82 (P=.22) before and after modifications, respectively, whereas the task completion score was 4.47, which improved to 4.58 (P=.39) after modifications. Following modifications for professional users, the SUS scores improved from 71 to 75 (P=.47), and the mean task performance improved significantly (4.40 vs 4.02; P=.001). Conclusions: Software modifications, informed by rigorous assessment, rendered a usable system, which is currently used in multiple NCI-sponsored multicenter cancer clinical trials

Imaging aspects of cardiovascular disease at the cell and molecular level

Cell and molecular imaging has a long and distinguished history. Erythrocytes were visualized microscopically by van Leeuwenhoek in 1674, and microscope technology has evolved mightily since the first single-lens instruments, and now incorporates many types that do not use photons of light for image formation. The combination of these instruments with preparations stained with histochemical and immunohistochemical markers has revolutionized imaging by allowing the biochemical identification of components at subcellular resolution. The field of cardiovascular disease has benefited greatly from these advances for the characterization of disease etiologies. In this review, we will highlight and summarize the use of microscopy imaging systems, including light microscopy, electron microscopy, confocal scanning laser microscopy, laser scanning cytometry, laser microdissection, and atomic force microscopy in conjunction with a variety of histochemical techniques in studies aimed at understanding mechanisms underlying cardiovascular diseases at the cell and molecular level

RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner.

Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B (PDGFB) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC

A generalised porous medium approach to study thermo-fluid dynamics in human eyes

The present work describes the application of the generalised porous medium model to study heat and fluid flow in healthy and glaucomatous eyes of different subject specimens, considering the presence of ocular cavities and porous tissues. The 2D computational model, implemented into the open-source software OpenFOAM, has been verified against benchmark data for mixed convection in domains partially filled with a porous medium. The verified model has been employed to simulate the thermo-fluid dynamic phenomena occurring in the anterior section of four patient-specific human eyes, considering the presence of anterior chamber (AC), trabecular meshwork (TM), Schlemm’s canal (SC), and collector channels (CC). The computational domains of the eye are extracted from tomographic images. The dependence of TM porosity and permeability on intraocular pressure (IOP) has been analysed in detail, and the differences between healthy and glaucomatous eye conditions have been highlighted, proving that the different physiological conditions of patients have a significant influence on the thermo-fluid dynamic phenomena. The influence of different eye positions (supine and standing) on thermo-fluid dynamic variables has been also investigated: results are presented in terms of velocity, pressure, temperature, friction coefficient and local Nusselt number. The results clearly indicate that porosity and permeability of TM are two important parameters that affect eye pressure distribution

Olive oil enriched diet suppresses hepatocellular carcinoma (HCC) tumor growth via focal adhesion pathway

Objective: Olive oil, an integral ingredient of the Mediterranean diet, has been suggested to have a potential role in lowering risk of several cancers. However, there is a lack of literature reporting the detailed mechanism of dietary olive oil on HCC. In this present study, we examine the effects of olive oil enriched diet on the genetic profile changes and the relation to malignancy and metastasis of HCC. Methodology: Human low metastatic hepatocellular carcinoma cell line (MHCC97L) was used in the orthotopic xenograft model. We analyzed the gene expression profile of HCC tumor implanted in nude mice, either fed with normal rat chow (n = 3) or 20% olive oil enriched diet (n = 3), by performing Affymetrix microarray analysis. Results: Tumor volume of nude mice fed with 20% olive oil diet was significantly reduced by 80%. Our microarray data showed that the molecular mechanism of HCC tumor growth suppression could be explained by focal adhesion pathway, which is particularly associated with cell migration and integrin signaling. The present study revealed olive oil-enriched diet down-regulated the genes expression of extracellular matrix (ECM)-linked focal adhesion pathway candidates, like ECM and protein kinase, alpha (PKCA), and insulin-like growth factor 1 (IGF-1)-linked focal adhesion pathway genes, such as met proto-oncogene (MET). In addition, the up-regulation of the c-Jun N-terminal Kinase (JNK) candidates, such as cell division cycle 42 (cdc42, GTP-binding protein), mitogen-activated protein kinase / extracellular signal regulated kinase kinase 1 (MEKK1) and mitogen-activated protein kinase kinase 7 (MKK7), by olive oil-enriched diet might contributed to the onset of apoptosis or cell cycle delay. Certainly, an appropriate study of the active component(s) in olive oil on HCC must be carried out to provide stronger evidence to a new molecular approach of diet intervention in the management of HCC

The cell cycle effects of docosahexaenoic acid on human metastatic hepatocellular carcinoma proliferation

Given the reported side effects associated with chemotherapy and surgical resection, dietary intervention with ω-3 polyunsaturated fatty acids (PUFAs) has been postulated to be an alterative way to prevent liver cancer progression and metastasis. We studied the effects of an ω-3 PUFA, docahexaenoic acid (DHA) on COX-2 expression and the cell cycle control machinery that co-ordinately regulate the HCC cells growth. Our data showed that DHA (0-200 μM) retarded proliferation of the human metastatic HCC cell line MHCC97L dose-dependently. In addition, inhibition of cyclin A/Cdk2 interfered with S-phase progression further in agreement with the result of bivariate flow cytometric analysis which indicated that DNA synthesis time (T s) was significantly prolonged by DHA in MHCC97L. The N-myc oncogene, the heat shock proteins Hsp27 and glucose-related protein 78 (GRP78) as well as the antioxidant enzymes superoxide dismutase may play significant roles in the cell cycle control and reduced-proliferation of MHCC97L by DHA. Our data indicated that it is imperative to develop therapeutic strategy with ω-3 PUFA that simultaneously targets COX-2 and other cell cycle regulators in hepatocarcinogenesis. This study provides novel mechanistic insights into the modulation of DHA on human hepatocarcinoma.link_to_OA_fulltex