Consequences of a Government-Controlled Agricultural Price Increase on Fishing and the Coral Reef Ecosystem in the Republic of Kiribati

Background

Economic development policies may have important economic and ecological consequences beyond the sector they target. Understanding these consequences is important to improving these policies and finding opportunities to align economic development with natural resource conservation. These issues are of particular interest to governments and non-governmental organizations that have new mandates to pursue multiple benefits. In this case study, we examined the direct and indirect economic and ecological effects of an increase in the government-controlled price for the primary agricultural product in the Republic of Kiribati, Central Pacific.

Methods/Principal Findings

We conducted household surveys and underwater visual surveys of the coral reef to examine how the government increase in the price of copra directly affected copra labor and indirectly affected fishing and the coral reef ecosystem. The islands of Kiribati are coral reef atolls and the majority of households participate in copra agriculture and fishing on the coral reefs. Our household survey data suggest that the 30% increase in the price of copra resulted in a 32% increase in copra labor and a 38% increase in fishing labor. Households with the largest amount of land in coconut production increased copra labor the most and households with the smallest amount of land in coconut production increased fishing the most. Our ecological data suggests that increased fishing labor may result in a 20% decrease in fish stocks and 4% decrease in coral reef-builders.

Conclusions/Significance

We provide empirical evidence to suggest that the government increase in the copra price in Kiribati had unexpected and indirect economic and ecological consequences. In this case, the economic development policy was not in alignment with conservation. These results emphasize the importance of accounting for differences in household capital and taking a systems approach to policy design and evaluation, as advocated by sustainable livelihood and ecosystem-based management frameworks.     

Direct Staining with Major Histocompatibility Complex Class II Dextramers Permits Detection of Antigen-Specific,Autoreactive CD4 T Cells In Situ

We report here the utility of major histocompatibility complex (MHC) class II dextramers for in situ detection of self-reactive CD4 T cells in two target organs, the brain and heart. We optimized the conditions for in situ detection of antigen-specific CD4 T cells using brain sections obtained from SJL mice immunized with myelin proteolipid protein (PLP) 139–151; the sections were costained with IA^s/PLP 139–151 (specific) or Theiler''s murine encephalomyelitis virus (TMEV) 70–86 (control) dextramers and anti-CD4. Analysis of sections by laser scanning confocal microscope revealed detection of cells positive for PLP 139–151 but not for TMEV 70–86 dextramers to be colocalized with CD4-expressing T cells, indicating that the staining was specific to PLP 139–151 dextramers. Further, we devised a method to reliably enumerate the frequencies of antigen-specific T cells by counting the number of dextramer⁺ CD4⁺ T cells in the ‘Z’ serial images acquired sequentially. We next extended these observations to detect cardiac myosin-specific T cells in autoimmune myocarditis induced in A/J mice by immunizing with cardiac myosin heavy chain-α (Myhc) 334–352. Heart sections prepared from immunized mice were costained with Myhc 334–352 (specific) or bovine ribonuclease 43–56 (control) dextramers together with anti-CD4; the sections showed the infiltrations of Myhc-specific CD4 T cells. The data suggest that MHC class II dextramers are useful tools for enumerating the frequencies of antigen-specific CD4 T cells in situ by direct staining without having to amplify the fluorescent signals, an approach commonly employed with conventional MHC tetramers.     

Lifecourse Adversity and Physical Performance across Countries among Men and Women Aged 65-74

Background

This study examines the associations between lifecourse adversity and physical performance in old age in different societies of North and South America and Europe.

Methods

We used data from the baseline survey of the International Study of Mobility in Aging, conducted in: Kingston (Canada), Saint-Hyacinthe (Canada), Natal (Brazil), Manizales (Colombia) and Tirana (Albania). The study population was composed of community dwelling people between 65 and 74 years of age, recruiting 200 men and 200 women at each site. Physical Performance was assessed with the Short Physical Performance Battery (SPPB). Economic and social adversity was estimated from childhood adverse events, low education, semi-skilled occupations during adulthood and living alone and insufficient income in old age.

Results

A total of 1995 people were assessed. Low physical performance was associated with childhood social and economic adversity, semi-skilled occupations, living alone and insufficient income. Physical performance was lower in participants living in Colombia, Brazil and Albania than in Canada counterparts, despite adjustment for lifecourse adversity, age and sex.

Conclusions

We show evidence of the early origins of social and economic inequalities in physical performance during old age in distinct populations and for the independent and cumulative disadvantage of low socioeconomic status during adulthood and poverty and living alone in later life.     

Virus Pathotype and Deep Sequencing of the HA Gene of a Low Pathogenicity H7N1 Avian Influenza Virus Causing Mortality in Turkeys

Low pathogenicity avian influenza (LPAI) viruses of the H7 subtype generally cause mild disease in poultry. However the evolution of a LPAI virus into highly pathogenic avian influenza (HPAI) virus results in the generation of a virus that can cause severe disease and death. The classification of these two pathotypes is based, in part, on disease signs and death in chickens, as assessed in an intravenous pathogenicity test, but the effect of LPAI viruses in turkeys is less well understood. During an investigation of LPAI virus infection of turkeys, groups of three-week-old birds inoculated with A/chicken/Italy/1279/99 (H7N1) showed severe disease signs and died or were euthanised within seven days of infection. Virus was detected in many internal tissues and organs from culled birds. To examine the possible evolution of the infecting virus to a highly pathogenic form in these turkeys, sequence analysis of the haemagglutinin (HA) gene cleavage site was carried out by analysing multiple cDNA amplicons made from swabs and tissue sample extracts employing Sanger and Next Generation Sequencing. In addition, a RT-PCR assay to detect HPAI virus was developed. There was no evidence of the presence of HPAI virus in either the virus used as inoculum or from swabs taken from infected birds. However, a small proportion (<0.5%) of virus carried in individual tracheal or liver samples did contain a molecular signature typical of a HPAI virus at the HA cleavage site. All the signature sequences were identical and were similar to HPAI viruses collected during the Italian epizootic in 1999/2000. We assume that the detection of HPAI virus in tissue samples following infection with A/chicken/Italy/1279/99 reflected amplification of a virus present at very low levels within the mixed inoculum but, strikingly, we observed no new HPAI virus signatures in the amplified DNA analysed by deep-sequencing.     

Suprafenacine,an Indazole-Hydrazide Agent,Targets Cancer Cells Through Microtubule Destabilization

Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule - 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G₂/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK - mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3. Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our results suggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents.     

High Resolution T1ρ Mapping of In Vivo Human Knee Cartilage at 7T

Purpose

Spin lattice relaxation time in rotating frame (T1ρ) mapping of human knee cartilage has shown promise in detecting biochemical changes during osteoarthritis. Due to higher field strength, MRI at 7T has advantages in term of SNR compared to clinical MR scanners and this can be used to increase in image resolution. Objective of current study was to evaluate the feasibility of high resolution T1ρ mapping of in vivo human knee cartilage at 7T MR scanner.

Materials and Methods

In this study we have used a T1ρ prepared GRE pulse sequence for obtaining high resolution (in plan resolution  = 0.2 mm²) T1ρ MRI of human knee cartilage at 7T. The effect of a global and localized reference frequency and reference voltage setting on B₀, B₁ and T1ρ maps in cartilage was evaluated. Test-retest reliability results of T1ρ values from asymptomatic subjects as well as T1ρ maps from abnormal cartilage of two human subjects are presented. These results are compared with T1ρ MRI data obtained from 3T.

Results

Our approach enabled acquisition of 3D-T1ρ data within allowed SAR limits at 7T. SNR of cartilage on T1ρ weighted images was greater than 90. Off-resonance effects present in the cartilage B₀, B₁ and T1ρ maps obtained using global shim and reference frequency and voltage setting, were reduced by the proposed localized reference frequency and voltage setting. T1ρ values of cartilage obtained with the localized approach were reproducible. Abnormal knee cartilage showed elevated T1ρ values in affected regions. T1ρ values at 7T were significantly lower (p<0.05) compared to those obtained at 3T.

Conclusion

In summary, by using proposed localized frequency and voltage setting approach, high-resolution 3D-T1ρ maps of in vivo human knee cartilage can be obtained in clinically acceptable scan times (<30 min) and SAR constraints, which provides the ability to characterize cartilage molecular integrity.     

Association of Common Genetic Variants with Lipid Traits in the Indian Population

Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations.     

S137 Phosphorylation of Profilin 1 Is an Important Signaling Event in Breast Cancer Progression

Background

Profilins are actin-modulating proteins regulating many intracellular functions based on their multiple and diverse ligand interactions. They have been implicated to play a role in many pathological conditions such as allergies, cardiovascular diseases, muscular atrophy, diabetes, dementia and cancer. Post-translational modifications of profilin 1 can alter its properties and subsequently its function in a cell. In the present study, we identify the importance of phosphorylation of profilin 1 at serine 137 (S137) residue in breast cancer progression.

Methods/Principal Findings

We found elevated profilin 1 (PFN) in human breast cancer tissues when compared to adjacent normal tissues. Overexpression of wild-type profilin 1 (PFN-WT) in breast cancer MCF7 cells made them more migratory, invasive and adherent independent in comparison to empty vector transfected cells. Mutation in serine phosphorylation site (S137) of profilin 1 (PFN-S137A) significantly abrogated these properties. Mutation affecting actin-binding ability (PFN-R74E) of profilin 1 enhanced its tumorigenic function whereas mutation affecting its poly-L-proline binding function (PFN-H133S) alleviated these mechanisms in breast cancer cells. PFN-WT was found to activate matrix metalloproteinases by zymography, MMP2 and MMP9 in presence of PDBu (phorbol 12, 13 dibutyrate, PI3K agonist) to enhance migration and invasion in MCF7 cells while PFN-S137A did not. Phosphorylation increased migration and invasion in other mutants of profilin 1. Nuclear profilin levels also increased in the presence of PDBu.

Conclusions

Previous studies show that profilin could be executing a dual role in cancer by either suppressing or promoting tumorigenesis in a context dependent manner. In this study we demonstrate for the first time that phosphorylation of profilin 1 at serine 137 enhances oncogenic properties in breast cancer cells. Inhibitors targeting profilin 1 phosphorylation directly or indirectly through inhibition of kinases that phosphorylate profilin could be valuable therapeutic agents that can alter its activity and thereby control the progression of cancer.     

Evaluation of Publicly Financed and Privately Delivered Model of Emergency Referral Services for Maternal and Child Health Care in India

Background

Emergency referral services (ERS) are being strengthened in India to improve access for institutional delivery. We evaluated a publicly financed and privately delivered model of ERS in Punjab state, India, to assess its extent and pattern of utilization, impact on institutional delivery, quality and unit cost.

Methods

Data for almost 0.4 million calls received from April 2012 to March 2013 was analysed to assess the extent and pattern of utilization. Segmented linear regression was used to analyse month-wise data on number of institutional deliveries in public sector health facilities from 2008 to 2013. We inspected ambulances in 2 districts against the Basic Life Support (BLS) standards. Timeliness of ERS was assessed for determining quality. Finally, we computed economic cost of implementing ERS from a health system perspective.

Results

On an average, an ambulance transported 3–4 patients per day. Poor and those farther away from the health facility had a higher likelihood of using the ambulance. Although the ERS had an abrupt positive effect on increasing the institutional deliveries in the unadjusted model, there was no effect on institutional delivery after adjustment for autocorrelation. Cost of operating the ambulance service was INR 1361 (USD 22.7) per patient transported or INR 21 (USD 0.35) per km travelled.

Conclusion

Emergency referral services in Punjab did not result in a significant change in public sector institutional deliveries. This could be due to high baseline coverage of institutional delivery and low barriers to physical access. Choice of interventions for reduction in Maternal Mortality Ratio (MMR) should be context-specific to have high value for resources spent. The ERS in Punjab needs improvement in terms of quality and reduction of cost to health system.