Optimal harvesting strategies for timber and non-timber forest products in tropical ecosystems

Harvesting wild plants for non-timber forest products (NTFPs) can be ecologically sustainable–without long-term consequences to the dynamics of targeted and associated species–but it may not be economically satisfying because it fails to provide enough revenues for local people over time. In several cases, the same species can be harvested for NTFP and also logged for timber. Three decades of studies on the sustainability of NTFP harvest for local people’s livelihood have failed to successfully integrate these socio-economic and ecological factors. We apply optimal control theory to investigate optimal strategies for the combinations of non-lethal (e.g., NTFP) and lethal (e.g., timber) harvest that minimize the cost of harvesting while maximizing the benefits (revenue) that accrue to harvesters and the conservation value of harvested ecosystems. Optimal harvesting strategies include starting with non-lethal NTFP harvest and postponing lethal timber harvesting to begin after a few years. We clearly demonstrate that slow growth species have lower optimal harvesting rates, objective functional values and profits than fast growth species. However, contrary to expectation, the effect of species lifespan on optimal harvesting rates was weak suggesting that life history is a better indicator of species resilience to harvest than lifespan. Overall, lethal or nonlethal harvest rates must be <40 % to ensure optimality. This optimal rate is lower than commonly reported sustainable harvest rates for non-timber forest products.     

A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion

Although dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E-DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane. Our data showed that DVD-1A1D-2A10 retained the antigen-binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-γ-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV.     

Endovascular Treatment with Stent-Retriever Devices for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Importance

Acute ischemic stroke is a leading cause of death and disability worldwide. Several recent clinical trials have shown that endovascular treatment improves clinical outcomes among patients with acute ischemic stroke.

Objective

To provide an overall and precise estimate of the efficacy of endovascular treatment predominantly using second-generation mechanical thrombectomy devices (stent-retriever devices) compared to medical management on clinical and functional outcomes among patients with acute ischemic stroke.

Data Sources

MEDLINE, EMBASE, Cochrane Collaboration Central Register of Controlled Clinical Trials, Web of Science, and NIH ClinicalTrials.gov were searched through November 2015.

Study Selection

Searches returned 3,045 articles. After removal of duplicates, two authors independently screened titles and abstracts to assess eligibility of 2,495 potentially relevant publications. From these, 38 full-text publications were more closely assessed. Finally, 5 randomized controlled trials of endovascular treatment with predominant use of retrievable stents were selected.

Data Extraction and Synthesis

Three authors independently extracted information on participant and trial characteristics and clinical events using a standardized protocol. Random effects models were used to pool endovascular treatment effects across outcomes.

Main Outcomes and Measures

The primary outcome was better functional outcome as measured on the modified Rankin Scale at 90 days of follow-up. Secondary outcomes included all-cause mortality and symptomatic intra-cerebral hemorrhage.

Results

Five trials representing 1,287 patients were included. Overall, patients randomized to endovascular therapy experienced 2.22 times greater odds of better functional outcome compared to those randomized to medical management (95% CI, 1.66 to 2.98; P < 0.0001). Endovascular therapy was not associated with mortality [OR (95% CI), 0.78 (0.54, 1.12); P = 0.1056] or symptomatic intracerebral hemorrhage [OR (95% CI), 1.19 (0.69, 2.05); P = 0.5348]. Meta-regression analysis suggested that shorter times from stroke onset to groin puncture and from stroke onset to reperfusion result in better functional outcomes in ischemic stroke patients (P = 0.0077 and P = 0.0089). There were no significant differences in the beneficial effects of endovascular treatment on functional outcomes across categories of gender, age, stroke severity, ischemic changes on computed tomography, or intravenous tissue plasminogen activator administration.

Conclusions and Relevance

This meta-analysis demonstrated superior functional outcomes in subjects receiving endovascular treatment compared to medical management. Further, this analysis showed that acute ischemic stroke patients may receive enhanced functional benefit from earlier endovascular treatment.     

Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.