Hepatoma-Derived Growth Factor-Related Protein-3 Is a Novel Angiogenic Factor

Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its in vitro and in vivo functional roles and molecular signaling. We combined open reading frame phage display with multi-round in vivo binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its in vitro angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase ½ (ERK1/2) pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, in vivo Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor.     

Diurnal and Seasonal Variations in Carbon Dioxide Exchange in Ecosystems in the Zhangye Oasis Area,Northwest China

Quantifying carbon dioxide exchange and understanding the response of key environmental factors in various ecosystems are critical to understanding regional carbon budgets and ecosystem behaviors. For this study, CO₂ fluxes were measured in a variety of ecosystems with an eddy covariance observation matrix between June 2012 and September 2012 in the Zhangye oasis area of Northwest China. The results show distinct diurnal variations in the CO₂ fluxes in vegetable field, orchard, wetland, and maize cropland. Diurnal variations of CO₂ fluxes were not obvious, and their values approached zero in the sandy desert, desert steppe, and Gobi ecosystems. Additionally, daily variations in the Gross Primary Production (GPP), Ecosystem Respiration (R_eco) and Net Ecosystem Exchange (NEE) were not obvious in the sandy desert, desert steppe, and Gobi ecosystems. In contrast, the distributions of the GPP, R_eco, and NEE show significant daily variations, that are closely related to the development of vegetation in the maize, wetland, orchard, and vegetable field ecosystems. All of the ecosystems are characterized by their carbon absorption during the observation period. The ability to absorb CO₂ differed significantly among the tested ecosystems. We also used the Michaelis-Menten equation and exponential curve fitting methods to analyze the impact of Photosynthetically Active Radiation (PAR) on the daytime CO₂ flux and impact of air temperature on R_eco at night. The results show that PAR is the dominant factor in controlling photosynthesis with limited solar radiation, and daytime CO₂ assimilation increases rapidly with PAR. Additionally, the carbon assimilation rate was found to increase slowly with high solar radiation. The light response parameters changed with each growth stage for all of the vegetation types, and higher light response values were observed during months or stages when the plants grew quickly. Light saturation points are different for different species. Nighttime R_eco increases exponentially with air temperature. High Q₁₀ values were observed when the vegetation coverage was relatively low, and low Q₁₀ values occurred when the vegetables grew vigorously.     

Genomic Analysis of a Mycobacterium Bovis Bacillus Calmette-Guérin Strain Isolated from an Adult Patient with Pulmonary Tuberculosis

For years, bacillus Calmette-Guérin (BCG) has served as the unique vaccine against tuberculosis and has generally been regarded as safe. However, a clinical strain labeled 3281 that was isolated from a TB patient was identified to be BCG. Via the combination of next-generation sequencing (NGS) and comparative genomic analysis, unique 3281 genetic characteristics were revealed. A region containing the dnaA and dnaN genes that is closely related to the initial chromosome replication was found to repeat three times on the BCG Pasteur-specific tandem duplication region DU1. Due to the minimum number of epitopes in BCG strains, 3281 was inferred to have a high possibility for immune evasion. Additionally, variations in the virulence genes and predictions for potential virulence factors were analyzed. Overall, we report a pathogen that has never previously been thought to be pathogenic and initial insights that are focused on the genetic characteristics of virulent BCG.     

Simple Plans or Sophisticated Habits? State,Transition and Learning Interactions in the Two-Step Task

The recently developed ‘two-step’ behavioural task promises to differentiate model-based from model-free reinforcement learning, while generating neurophysiologically-friendly decision datasets with parametric variation of decision variables. These desirable features have prompted its widespread adoption. Here, we analyse the interactions between a range of different strategies and the structure of transitions and outcomes in order to examine constraints on what can be learned from behavioural performance. The task involves a trade-off between the need for stochasticity, to allow strategies to be discriminated, and a need for determinism, so that it is worth subjects’ investment of effort to exploit the contingencies optimally. We show through simulation that under certain conditions model-free strategies can masquerade as being model-based. We first show that seemingly innocuous modifications to the task structure can induce correlations between action values at the start of the trial and the subsequent trial events in such a way that analysis based on comparing successive trials can lead to erroneous conclusions. We confirm the power of a suggested correction to the analysis that can alleviate this problem. We then consider model-free reinforcement learning strategies that exploit correlations between where rewards are obtained and which actions have high expected value. These generate behaviour that appears model-based under these, and also more sophisticated, analyses. Exploiting the full potential of the two-step task as a tool for behavioural neuroscience requires an understanding of these issues.     

Synthesis and in Vitro Antiviral Activities of [(Dihydrofuran‐2‐yl)oxy]methyl‐phosphonate Nucleosides with 2‐Substituted Adenine as Base

The synthesis of [(2′,5′‐dihydrofuran‐2‐yl)oxy]methyl‐phosphonate nucleosides with a 2‐substituted adenine base moiety starting from 2‐deoxy‐3,5‐bis‐O‐(4‐methylbenzoyl)‐α‐L ‐ribofuranosyl chloride and 2,6‐dichloropurine is described. The key step is the regiospecific and stereoselective introduction of a phosphonate synthon at C(2) of the furan ring. None of the synthesized compounds showed significant in vitro activity against HIV, BVDV, and HBV.