Mechanistic insights into the effects of climate change on larval cod

Understanding the biophysical mechanisms that shape variability in fisheries recruitment is critical for estimating the effects of climate change on fisheries. In this study, we used an Earth System Model (ESM) and a mechanistic individual‐based model (IBM) for larval fish to analyze how climate change may impact the growth and survival of larval cod in the North Atlantic. We focused our analysis on five regions that span the current geographical range of cod and are known to contain important spawning populations. Under the SRES A2 (high emissions) scenario, the ESM‐projected surface ocean temperatures are expected to increase by >1 °C for 3 of the 5 regions, and stratification is expected to increase at all sites between 1950–1999 and 2050–2099. This enhanced stratification is projected to decrease large (>5 μm ESD) phytoplankton productivity and mesozooplankton biomass at all 5 sites. Higher temperatures are projected to increase larval metabolic costs, which combined with decreased food resources will reduce larval weight, increase the probability of larvae dying from starvation and increase larval exposure to visual and invertebrate predators at most sites. If current concentrations of piscivore and invertebrate predators are maintained, larval survival is projected to decrease at all five sites by 2050–2099. In contrast to past observed responses to climate variability in which warm anomalies led to better recruitment in cold‐water stocks, our simulations indicated that reduced prey availability under climate change may cause a reduction in larval survival despite higher temperatures in these regions. In the lower prey environment projected under climate change, higher metabolic costs due to higher temperatures outweigh the advantages of higher growth potential, leading to negative effects on northern cod stocks. Our results provide an important first large‐scale assessment of the impacts of climate change on larval cod in the North Atlantic.     

Synthesis, molecular modeling studies and biological evaluation of fluorine substituted analogs of GW 501516

(±)-2-Fluoro-2-(2-methyl-4-(((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methyl)thio)phenoxy)acetic acid (2a) has been prepared and subjected to biological testing against all three subtypes of the PPARs. This compound exhibited agonist effects with EC(50) values of 560 and 55 nM against PPARα and PPARδ, respectively, in a luciferase assay. Moreover, compound (±)-2a also exhibited potent ability to induce oleic acid oxidation in a human myotube cell assay with EC(50)=3.7 nM. Compound (±)-2a can be classified as a dual PPARα/δ agonist with a 10-fold higher potency against the PPARδ receptor than against the PPARα receptor. Molecular modeling studies revealed that both enantiomers of 2a bind to the PPARδ receptor with similar binding energies.     

Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptor class B type I

Pregnane X receptor (PXR) is the molecular target for a wide variety of endogenous and xenobiotic compounds. It regulates the expression of genes central to the detoxification (cytochrome P-450 enzymes) and excretion (xenobiotic transporters) of potentially harmful compounds. The aim of the present investigation was to determine the role of PXR in regulation of high-density lipoprotein (HDL) cholesterol metabolism by studying its impact on ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) expression in hepatocytes. ABCA1 and SR-BI are major factors in the exchange of cholesterol between cells and HDL. Expression analyses were performed using Western blotting and quantitative real time RT-PCR. Luciferase reporter gene assays were used to measure promoter activities. Total cholesterol was measured enzymatically after lipid extraction (Folch's method). The expression of ABCA1 and SR-BI was inhibited by the PXR activators rifampicin and lithocholic acid (LCA) in HepG2 cells and pregnenolone 16alpha-carbonitrile (PCN) in primary rat hepatocytes. Thus, PXR appears to be a regulator of hepatic cholesterol transport by inhibiting genes central to cholesterol uptake (SR-BI) and efflux (ABCA1).     

One-pot, mix-and-read peptide-MHC tetramers

Background

Cytotoxic T Lymphocytes (CTL) recognize complexes of peptide ligands and Major Histocompatibility Complex (MHC) class I molecules presented at the surface of Antigen Presenting Cells (APC). Detection and isolation of CTL''s are of importance for research on CTL immunity, and development of vaccines and adoptive immune therapy. Peptide-MHC tetramers have become important reagents for detection and enumeration of specific CTL''s. Conventional peptide-MHC-tetramer production involves recombinant MHC production, in vitro refolding, biotinylation and tetramerization; each step followed by various biochemical steps such as chromatographic purification, concentration etc. Such cumbersome production protocols have limited dissemination and restricted availability of peptide-MHC tetramers effectively precluding large-scale screening strategies involving many different peptide-MHC tetramers.

Methodology/Principal Findings

We have developed an approach whereby any given tetramer specificity can be produced within 2 days with very limited effort and hands-on time. The strategy is based on the isolation of correctly oxidized, in vivo biotinylated recombinant MHC I heavy chain (HC). Such biotinylated MHC I HC molecules can be refolded in vitro, tetramerized with streptavidin, and used for specific T cell staining-all in a one-pot reaction without any intervening purification steps.

Conclusions/Significance

We have developed an efficient “one-pot, mix-and-read” strategy for peptide-MHC tetramer generation, and demonstrated specific T cell straining comparable to a commercially available MHC-tetramer. Here, seven peptide-MHC tetramers representing four different human MHC (HLA) class I proteins have been generated. The technique should be readily extendable to any binding peptide and pre-biotinylated MHC (at this time we have over 40 different pre-biotinylated HLA proteins). It is simple, robust, and versatile technique with a very broad application potential as it can be adapted both to small- and large-scale production of one or many different peptide-MHC tetramers for T cell isolation, or epitope screening.     

CSPP Is a Ciliary Protein Interacting with Nephrocystin 8 and Required for Cilia Formation

We described previously the cell cycle- and microtubule-related functions of two splice isoforms of the centrosome spindle pole-associated protein (CSPP and CSPP-L). Here, we show that endogenous CSPP isoforms not only localize to centrosomes and the midbody in cycling cells but also extend to the cilia axoneme in postmitotic resting cells. They are required for ciliogenesis in hTERT-RPE1 cells in vitro and are expressed in ciliated renal, retinal, and respiratory cells in vivo. We report that CSPP isoforms require their common C-terminal domain to interact with Nephrocystin 8 (NPHP8/RPGRIP1L) and to form a ternary complex with NPHP8 and NPHP4. We find CSPP-L to be required for the efficient localization of NPHP8 but not NPHP4 to the basal body. The ciliogenesis defect in hTERT-RPE1 cells is, however, not mediated through loss of NPHP8. Similar to the effects of ectopical expression of CSPP-L, cilia length increased in NPHP8-depleted cells. Our results thus suggest that CSPP proteins may be involved in further cytoskeletal organization of the basal body and its primary cilium. To conclude, we have identified a novel, nonmitotic function of CSPP proteins placing them into a ciliary protein network crucial for normal renal and retinal tissue architecture and physiology.     

Bodyweight Changes Are Associated with Reduced Health Related Quality of Life: The Hordaland Health Study

There is lack of studies investigating the association between bodyweight changes and health related quality of life (HRQL). The aim was to study the effect of relative changes in bodyweight over time on HRQL. In the Hordaland Health Study, 9276 men and 10433 women aged 40–47 years were included. Weight and height were measured and information on bodyweight changes during the last 5 years, physical activity and smoking was obtained from self–administered questionnaires including the Medical Outcomes Study MOS short form-12 including a Physical health Composite Score (PCS) and a Mental health Composite Score (MCS). Increasing bodyweight changes were associated with marked reduced scores in PCS and MCS also after adjustment for body mass index (BMI), physical activity and smoking. Men and women with a variation in weight with more than 15% during the last 5 years reported a mean score of MCS that was 0.48 standard deviation (SD) (3.9/8.1) and 0.35 SD (3.1/8.9) lower than those reporting a variation in weight less than 5%. No major differences were found between those who at date of examination were at the lower and higher end of the reported weight interval. There were no significant differences in the associations between men and women. Our findings confirm that increasing bodyweight changes are associated with reduced physical and mental health beyond what is related to BMI itself.     

Comparing different methods for trapping mated queens of weaver ants (Oecophylla longinoda; Hymenoptera: Formicidae)

The predatory efficiency of African weaver ants Oecophylla longinoda and their utilisation in protein production is a function of ant abundance. Reliable control of insect pests in tropical crops is achieved when ant populations are constantly high. Transplanted populations of weaver ant colonies containing egg-laying queens are more stable than those without. Achieving such stability through collection of colonies established in the wild is usually difficult because of uncertainty in locating the nest containing the egg-laying queen. In this study, we investigated four methods that may be used to collect mated queens that subsequently can be used to stock ant nurseries. The catch efficiencies of (1) leaf traps, (2) paper traps (both types providing a refuge for founding queens), (3) random search for queens and (4) light trapping were compared. Light trapping was the most efficient way to collect queens followed by leaf traps, random search and, last, paper traps. Light trapping and random search, though, required the presence of a person throughout the ant's mating season (several months), whereas this was not required when using leaf and paper traps.