Sixteen years of social and ecological dynamics reveal challenges and opportunities for adaptive management in sustaining the commons.

Efforts to confront the challenges of environmental change and uncertainty include attempts to adaptively manage social-ecological systems. However, critical questions remain about whether adaptive management can lead to sustainable outcomes for both ecosystems and society. Here, we make a contribution to these efforts by presenting a 16-y analysis of ecological outcomes and perceived livelihood impacts from adaptive coral reef management in Papua New Guinea. The adaptive management system we studied was a customary rotational fisheries closure system (akin to fallow agriculture), which helped to increase the biomass of reef fish and make fish less wary (more catchable) relative to openly fished areas. However, over time the amount of fish in openly fished reefs slowly declined. We found that, overall, resource users tended to have positive perceptions about this system, but there were negative perceptions when fishing was being prohibited. We also highlight some of the key traits of this adaptive management system, including 1) strong social cohesion, whereby leaders played a critical role in knowledge exchange; 2) high levels of compliance, which was facilitated via a "carrot-and-stick" approach that publicly rewarded good behavior and punished deviant behavior; and 3) high levels of participation by community actors.

A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders.

Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer.

INTRODUCTION: Tubulin inhibitors including taxanes and vinca alkaloids are important components of chemotherapy regimens used in advanced non-small cell lung cancer (NSCLC). Despite a treatment paradigm shift due to molecularly-targeted therapies and immunotherapy, a majority of patients will receive chemotherapy during their treatment course. Either used alone or in combination, tubulin inhibitors have demonstrated clinical benefits in different settings of lung cancer management. Areas covered: This review first discusses FDA-approved tubulin inhibitors for NSCLC, such as paclitaxel, docetaxel, vinorelbine, and nab-paclitaxel. The article then provides a summary of novel tubulin inhibitors, including cabazitaxel, eribulin, ixabepilone, patupilone, plinabulin, new colchicine analogues and others. It also discusses new tubulin inhibitor combinations with immunotherapy (PD-1/PD-L1 inhibitors) and molecularly-targeted therapies (e.g. anti-angiogenic agents, mTOR inhibitors, heat shock protein 90 inhibitors, MEK inhibitors, and anti-HER3 agents). Lastly, emerging data on potential resistance mechanisms and predictive biomarkers for tubulin inhibitors are explored. Expert opinion: Tubulin inhibitors will likely continue to play important roles in NSCLC management due to the advent of novel agents and combinations. Through further understanding of tumor biology, investigation of drug resistance, and development of predictive biomarkers, we will be better positioned to incorporate microtubule inhibition into patient specific treatment strategies.

Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4.

The four members of the ErbB family of receptor tyrosine kinases are involved in development and tumorigenesis of the mammary gland. Whereas the epidermal growth factor receptor, ErbB2 and ErbB3 are positively associated with various cancers, clinical studies of ErbB4 in breast cancer are contradictory. Results from tissue culture analyses and some clinical studies suggested that ErbB4 is either a tumor suppressor or is a negative regulator of ErbB2-driven tumors. Neu-Cre-ErbB4(flox/null) mice in which ErbB4 was inactivated by Cre-lox-mediated recombination in the mammary gland developed MMTV-Neu-driven mammary tumors with a similar latency period to mice with one or two wild-type ErbB4 alleles. Moreover, there was no difference in the histologies of tumors that developed, nor in the propensity to form lung metastases. Taken together these results suggest that ErbB4 is not a potent, highly penetrant tumor suppressor, nor is it a factor in Neu-mediated tumorigenesis in this model.

Hepatitis B Seroprevalence Study 1999.

Hepatitis B is a disease of public health importance in Singapore. A study was conducted in 1999 to estimate the overall and gender-, age- and ethnic-specific prevalence of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and antibody to hepatitis B surface antigen in the Singapore population. A cross-sectional sample of the Singapore population constituting 4,698 Singapore residents aged 18-69 years was surveyed. This was the first time a large-scale study has been conducted to assess the hepatitis B seroprevalence rates in the Singapore population. The overall prevalence of the HBsAg in the general population was estimated to be about 4%. About 13% of the HBsAg carriers were also HBeAg positive. Only about 40% of the population had immunity to hepatitis B virus either through immunisation or from previous exposure to the virus. There was still a large proportion (60%) of the population who had no immunity, especially the younger age group of 18-29 years where only 28% had immunity. There is a need to strengthen the hepatitis B immunisation programme to reach out to those who have no immunity, especially the young adults.