Environmental Enrichment Induces Behavioral Recovery and Enhanced Hippocampal Cell Proliferation in an Antidepressant-Resistant Animal Model for PTSD

Background: Post traumatic stress disorder (PTSD) can be considered the result of a failure to recover after a traumatic experience. Here we studied possible protective and therapeutic aspects of environmental enrichment (with and without a running wheel) in Sprague Dawley rats exposed to an inescapable foot shock procedure (IFS). Methodology/Principal Findings: IFS induced long-lasting contextual and non-contextual anxiety, modeling some aspects of PTSD. Even 10 weeks after IFS the rats showed reduced locomotion in an open field. The antidepressants imipramine and escitalopram did not improve anxiogenic behavior following IFS. Also the histone deacetylase (HDAC) inhibitor sodium butyrate did not alleviate the IFS induced immobility. While environmental enrichment (EE) starting two weeks before IFS did not protect the animals from the behavioral effects of the shocks, exposure to EE either immediately after the shock or one week later induced complete recovery three weeks after IFS. In the next set of experiments a running wheel was added to the EE to enable voluntary exercise (EE/VE). This also led to reduced anxiety. Importantly, this behavioral recovery was not due to a loss of memory for the traumatic experience. The behavioral recovery correlated with an increase in cell proliferation in hippocampus, a decrease in the tissue levels of noradrenalin and increased turnover of 5-HT in prefrontal cortex and hippocampus. Conclusions/Significance: This animal study shows the importance of (physical) exercise in the treatment of psychiatri

Common and specific downstream signaling targets controlled by Tlr2 and Tlr5 innate immune signaling in zebrafish

BACKGROUND: Although the responses to many pathogen associated molecular patterns (PAMPs) in cell cultures and extracted organs are well characterized, there is little known of transcriptome responses to PAMPs in whole organisms. To characterize this in detail, we have performed RNAseq analysis of responses of zebrafish embryos to injection of PAMPs in the caudal vein at one hour after exposure. We have compared two ligands that in mammals have been shown to specifically activate the TLR2 and TLR5 receptors: Pam3CSK4 and flagellin, respectively. RESULTS: We identified a group of 80 common genes that respond with high stringency selection to stimulations with both PAMPs, which included several well-known immune marker genes such as il1b and tnfa. Surprisingly, we also identified sets of 48 and 42 genes that specifically respond to either Pam3CSK4 or flagellin, respectively, after a comparative filtering approach. Remarkably, in the Pam3CSK4 specific set, there was a set of transcription factors with more than 2 fold-change, as confirmed by qPCR analyses, including cebpb, fosb, nr4a1 and egr3. We also showed that the regulation of the Pam3CSK4 and flagellin specifically responding sets is inhibited by knockdown of tlr2 or tlr5, respectively. CONCLUSIONS: Our studies show that Pam3CSK4 and flagellin can stimulate the Tlr2 and Tlr5 signaling pathways leading to common and specific responses in the zebrafish embryo system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1740-9) contains supplementary material, which is available to authorized users

Contribution of Cattle Production to Livelihood of Smallholders Living Around Teak Forest in Bojonegoro, East Java

Beef cattle are important in Indonesia whereas the highest population of cattle is in East Java. The majority of cattle is kept by smallholders and some of smallholders living near to the teak forest. The existence of teak forest may provide potential income for smallholders, and drive their livelihood strategies. However, it is not known yet how much cattle production contributes to smallholder livelihoods, especially for smallholders living close to teak forests. The present study had the objective to assest contribution of cattle production to the livelihood of smallholders living near to teak forests. We interviewed 33 and 27 respondents (smallholder farmers with beef cattle as one of the farm activities) in Napis and Windu hamlets, respectively, of Napis village, Bojonegoro Regency, East Java. Cattle production contributed for 19.8% to the total household income and was the second most important income generating activity after crop production (48.5%). It was followed by income from non-farm activities (14.2%), forest (10%), off-farm activities (5.4%) and other livestock (2.1%). Since limited number of livelihood strategies to increase income in the study areas, keeping cattle is suggested as a potential livelihood strategy for smallholders to elevate their household income and welfare

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma

PURPOSE: MEDI0680 is a humanized anti-programmed cell death-1 (PD-1) antibody, and durvalumab is an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase II study evaluated antitumor activity and safety of MEDI0680 plus durvalumab versus nivolumab monotherapy in immunotherapy-naïve patients with advanced clear-cell renal cell carcinoma who received at least one prior line of antiangiogenic therapy. PATIENTS AND METHODS: Patients received either MEDI0680 (20 mg/kg) with durvalumab (750 mg) or nivolumab (240 mg), all intravenous, every 2 weeks. The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included best overall response, progression-free survival (PFS), safety, overall survival (OS), and immunogenicity. Exploratory endpoints included changes in circulating tumor DNA (ctDNA), baseline tumor mutational burden, and tumor-infiltrated immune cell profiles. RESULTS: Sixty-three patients were randomized (combination, n = 42; nivolumab, n = 21). ORR was 16.7% [7/42; 95% confidence interval (CI), 7.0-31.4] with combination treatment and 23.8% (5/21; 95% CI, 8.2-47.2) with nivolumab. Median PFS was 3.6 months in both arms; median OS was not reached in either arm. Because of adverse events, 23.8% of patients discontinued MEDI0680 and durvalumab and 14.3% of patients discontinued nivolumab. In the combination arm, reduction in ctDNA fraction was associated with longer PFS. ctDNA mutational analysis did not demonstrate an association with response in either arm. Tumor-infiltrated immune profiles showed an association between immune cell activation and response in the combination arm. CONCLUSIONS: MEDI0680 combined with durvalumab was safe and tolerable; however, it did not improve efficacy versus nivolumab monotherapy

Special topics--Mitigation of methane and nitrous oxide emissions from animal operations: III. A review of animal management mitigation options.

The goal of this review was to analyze published data on animal management practices that mitigate enteric methane (CH4) and nitrous oxide (N2O) emissions from animal operations. Increasing animal productivity can be a very effective strategy for reducing greenhouse gas (GHG) emissions per unit of livestock product. Improving the genetic potential of animals through planned cross-breeding or selection within breeds and achieving this genetic potential through proper nutrition and improvements in reproductive efficiency, animal health, and reproductive lifespan are effective approaches for improving animal productivity and reducing GHG emission intensity. In subsistence production systems, reduction of herd size would increase feed availability and productivity of individual animals and the total herd, thus lowering CH4 emission intensity. In these systems, improving the nutritive value of low-quality feeds for ruminant diets can have a considerable benefit on herd productivity while keeping the herd CH4 output constant or even decreasing it. Residual feed intake may be a tool for screening animals that are low CH4 emitters, but there is currently insufficient evidence that low residual feed intake animals have a lower CH4 yield per unit of feed intake or animal product. Reducing age at slaughter of finished cattle and the number of days that animals are on feed in the feedlot can significantly reduce GHG emissions in beef and other meat animal production systems. Improved animal health and reduced mortality and morbidity are expected to increase herd productivity and reduce GHG emission intensity in all livestock production systems. Pursuing a suite of intensive and extensive reproductive management technologies provides a significant opportunity to reduce GHG emissions. Recommended approaches will differ by region and species but should target increasing conception rates in dairy, beef, and buffalo, increasing fecundity in swine and small ruminants, and reducing embryo wastage in all species. Interactions among individual components of livestock production systems are complex but must be considered when recommending GHG mitigation practices

Special topics--Mitigation of methane and nitrous oxide emissions from animal operations: III. A review of animal management mitigation options.

The goal of this review was to analyze published data on animal management practices that mitigate enteric methane (CH4) and nitrous oxide (N2O) emissions from animal operations. Increasing animal productivity can be a very effective strategy for reducing greenhouse gas (GHG) emissions per unit of livestock product. Improving the genetic potential of animals through planned cross-breeding or selection within breeds and achieving this genetic potential through proper nutrition and improvements in reproductive efficiency, animal health, and reproductive lifespan are effective approaches for improving animal productivity and reducing GHG emission intensity. In subsistence production systems, reduction of herd size would increase feed availability and productivity of individual animals and the total herd, thus lowering CH4 emission intensity. In these systems, improving the nutritive value of low-quality feeds for ruminant diets can have a considerable benefit on herd productivity while keeping the herd CH4 output constant or even decreasing it. Residual feed intake may be a tool for screening animals that are low CH4 emitters, but there is currently insufficient evidence that low residual feed intake animals have a lower CH4 yield per unit of feed intake or animal product. Reducing age at slaughter of finished cattle and the number of days that animals are on feed in the feedlot can significantly reduce GHG emissions in beef and other meat animal production systems. Improved animal health and reduced mortality and morbidity are expected to increase herd productivity and reduce GHG emission intensity in all livestock production systems. Pursuing a suite of intensive and extensive reproductive management technologies provides a significant opportunity to reduce GHG emissions. Recommended approaches will differ by region and species but should target increasing conception rates in dairy, beef, and buffalo, increasing fecundity in swine and small ruminants, and reducing embryo wastage in all species. Interactions among individual components of livestock production systems are complex but must be considered when recommending GHG mitigation practices