Conservation of Salmonella Infection Mechanisms in Plants and Animals

Salmonella virulence in animals depends on effectors injected by Type III Secretion Systems (T3SSs). In this report we demonstrate that Salmonella mutants that are unable to deliver effectors are also compromised in infection of Arabidopsis thaliana plants. Transcriptome analysis revealed that in contrast to wild type bacteria, T3SS mutants of Salmonella are compromised in suppressing highly conserved Arabidopsis genes that play a prominent role during Salmonella infection of animals. We also found that Salmonella originating from infected plants are equally virulent for human cells and mice. These results indicate a high degree of conservation in the defense and infection mechanism of animal and plant hosts during Salmonella infection

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

Free Vibration Analysis and Seismic Performance Assessment of Two Approach Viaducts of Bosphorus Suspension Bridge

The current study aims to determine the dynamic vibration characteristics and structural earthquake performance of the approach viaducts of Bosphorus Suspension Bridge. Ortakoy viaduct at European continent and Beylerbeyi viaduct at Asian continent have a length of 231 and 235 m, and five spans and four spans, respectively. The viaducts are side span of the bridge and are supported at the base instead of hanger elements. Based on the project specifications of the viaducts, 3-D detailed finite element model of the viaducts is developed by the use of frame-elements, and natural frequencies and corresponding mode shapes of the viaducts are presented in the study. Paying attention to these considerations, pushover (POA) and nonlinear time-history analysis (NTHA) are performed to attain structural-earthquake performance of the viaducts according to Turkish code for the earthquake design of railways bridges (TSC-R/2008) and Caltrans (CALTRANS-2001) seismic design of steel bridge. Accordingly, the earthquake performance of the bridge is presented for each non-linear analysis method considering these codes

'Clusters' of innovations in recent long span and multi-segmental bridges

The system-level impacts of innovations often can be more significant than the direct, primary impacts in certain industries. In particular, these system interactions can be seen with large, complex multi-system constructed facilities. Approximately half of the 200 specific innovations identified in eleven recent long span and multi-segmental bridges are linked to other innovations. Three general types of 'cluster' interaction are system, actualizing, and complementary links. The system interactions are nurtured through coordinated innovation development programmes. The actualizing links connect one set of innovations to another set, to aid in their realization of the innovation and project objectives. The complementary links provide additional benefits through the joint use of multiple innovations. The results of these analyses provide significant new insight for innovation theory into the system-level interactions of innovations. Since the frequency of the linkages among the innovations appears to reflect the relative stability of the design and construction parameters, recent innovation trajectories may be more difficult to link effectively to other innovations. These innovation interactions can provide critical capabilities for achieving the project objectives, but must be identified and managed effectively to achieve desired performance levels.Construction Innovations Long Span Bridge Design And Construction System Interactions,

Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C

Background and Aims: Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. Methods: 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. Results: All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10–0.55; P<.001). Conclusions: Hepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results