Interacting forces of predation and fishing affect species’ maturation size

1. Fishing is a strong selective force and is supposed to select for earlier maturation at smaller body size. However, the extent to which fishing‐induced evolution is shaping ecosystems remains debated. This is in part because it is challenging to disentangle fishing from other selective forces (e.g., size‐structured predation and cannibalism) in complex ecosystems undergoing rapid change.
2. Changes in maturation size from fishing and predation have previously been explored with multi‐species physiologically structured models but assumed separation of ecological and evolutionary timescales. To assess the eco‐evolutionary impact of fishing and predation at the same timescale, we developed a stochastic physiologically size‐structured food‐web model, where new phenotypes are introduced randomly through time enabling dynamic simulation of species'' relative maturation sizes under different types of selection pressures.
3. Using the model, we carried out a fully factorial in silico experiment to assess how maturation size would change in the absence and presence of both fishing and predation (including cannibalism). We carried out ten replicate stochastic simulations exposed to all combinations of fishing and predation in a model community of nine interacting fish species ranging in their maximum sizes from 10 g to 100 kg. We visualized and statistically analyzed the results using linear models.
4. The effects of fishing on maturation size depended on whether or not predation was enabled and differed substantially across species. Fishing consistently reduced the maturation sizes of two largest species whether or not predation was enabled and this decrease was seen even at low fishing intensities (F = 0.2 per year). In contrast, the maturation sizes of the three smallest species evolved to become smaller through time but this happened regardless of the levels of predation or fishing. For the four medium‐size species, the effect of fishing was highly variable with more species showing significant and larger fishing effects in the presence of predation.
5. Ultimately our results suggest that the interactive effects of predation and fishing can have marked effects on species'' maturation sizes, but that, at least for the largest species, predation does not counterbalance the evolutionary effect of fishing. Our model also produced relative maturation sizes that are broadly consistent with empirical estimates for many fish species.

     

Malaria Parasite-Infected Erythrocytes Secrete PfCK1, the Plasmodium Homologue of the Pleiotropic Protein Kinase Casein Kinase 1

Casein kinase 1 (CK1) is a pleiotropic protein kinase implicated in several fundamental processes of eukaryotic cell biology. Plasmodium falciparum encodes a single CK1 isoform, PfCK1, that is expressed at all stages of the parasite’s life cycle. We have previously shown that the pfck1 gene cannot be disrupted, but that the locus can be modified if no loss-of-function is incurred, suggesting an important role for this kinase in intra-erythrocytic asexual proliferation. Here, we report on the use of parasite lines expressing GFP- or His-tagged PfCK1 from the endogenous locus to investigate (i) the dynamics of PfCK1 localisation during the asexual cycle in red blood cells, and (ii) potential interactors of PfCK1, so as to gain insight into the involvement of the enzyme in specific cellular processes. Immunofluorescence analysis reveals a dynamic localisation of PfCK1, with evidence for a pool of the enzyme being directed to the membrane of the host erythrocyte in the early stages of infection, followed by a predominantly intra-parasite localisation in trophozoites and schizonts and association with micronemes in merozoites. Furthermore, we present strong evidence that a pool of enzymatically active PfCK1 is secreted into the culture supernatant, demonstrating that PfCK1 is an ectokinase. Our interactome experiments and ensuing kinase assays using recombinant PfCK1 to phosphorylate putative interactors in vitro suggest an involvement of PfCK1 in many cellular processes such as mRNA splicing, protein trafficking, ribosomal, and host cell invasion.     

Axial Diffusivity of the Corona Radiata at 24 Hours Post-Stroke: A New Biomarker for Motor and Global Outcome

Fractional anisotropy (FA) is an effective marker of motor outcome at the chronic stage of stroke yet proves to be less efficient at early time points. This study aims to determine which diffusion metric in which location is the best marker of long-term stroke outcome after thrombolysis with diffusion tensor imaging (DTI) at 24 hours post-stroke. Twenty-eight thrombolyzed patients underwent DTI at 24 hours post-stroke onset. Ipsilesional and contralesional FA, mean (MD), axial (AD), and radial (RD) diffusivities values were calculated in different Regions-of-Interest (ROIs): (1) the white matter underlying the precentral gyrus (M1), (2) the corona radiata (CoRad), (3) the posterior limb of the internal capsule (PLIC) and (4) the cerebral peduncles (CP). NIHSS scores were acquired at admission, day 1, and day 7; modified Rankin Scores (mRS) at 3 months. Significant decreases were found in FA, MD, and AD of the ipsilesional CoRad and M1. MD and AD were also significantly lower in the PLIC. The ratio of ipsi and contralesional AD of the CoRad (CoRad-rAD) was the strongest diffusion parameter correlated with motor NIHSS scores on day 7 and with the mRS at 3 months. A Receiver-Operator Curve analysis yielded a model for the CoRad-rAD to predict good outcome based on upper limb NIHSS motor scores and mRS with high specificity and sensitivity. FA values were not correlated with clinical outcome. In conclusion, axial diffusivity of the CoRad from clinical DTI at 24 hours post-stroke is the most appropriate diffusion metric for quantifying stroke damage to predict outcome, suggesting the importance of early axonal damage.     

Mechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis

HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses’ receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART.     

Quantitative X-ray microanalysis of calcium with the Camebax-TEM system in frozen,freeze-substituted and resin-embedded tissue sections

Summary The relevance of the continuum method for a quantitative X-ray microanalysis of epon embedded tissue sections in the particular conditions offered by the Camebax-TEM system was tested and an improved model of specimen holder is proposed.The absolute calcium concentration [Ca] of membrane-bound intracellular glio-interstitial granules was determined by X-ray microanalysis in transmission electron microscopy of Mytilus retractor muscle. The Ca peak and background values were measured by the wavelength-dispersive spectrometer of the Camebax; the mass thickness of the section was recorded simultaneously with an added energy-dispersive detector. The tissue was frozen at 77 K in a mixture of liquid propane and butane, freeze-substituted in the presence of oxalic acid and embedded in epoxy resin. The calcium concentration of glio-intestitial granules can be as high as 180 mmol·kg^–1 of epoxy-embedded tissue, with an average of 40 mmol·kg^–1. The sampling of the data through repcated experiments is discussed and it is proposed that the cell would be the main level of variation. The Ca content of glio-interstitial granules is significantly lower in the tissbes of animals submitted to high-potassium artificial seawater for 10 min. This finding was predicted by the hypothesis that glio-interstitial tissue is a regulator of calcium concentration in extracellular spaces.     

A human histone H2B.1 variant gene, located on chromosome 1, utilizes alternative 3' end processing.

A variant human H2B histone gene (GL105), previously shown to encode a 2300 nt replication independent mRNA, has been cloned. We demonstrate this gene expresses alternative mRNAs regulated differentially during the HeLa S3 cell cycle. The H2B-Gl105 gene encodes both a 500 nt cell cycle dependent mRNA and a 2300 nt constitutively expressed mRNA. The 3' end of the cell cycle regulated mRNA terminates immediately following the region of hyphenated dyad symmetry typical of most histone mRNAs, whereas the constitutively expressed mRNA has a 1798 nt non-translated trailer that contains the same region of hyphenated dyad symmetry but is polyadenylated. The cap site for the H2B-GL105 mRNAs is located 42 nt upstream of the protein coding region. The H2B-GL105 histone gene was localized to chromosome region 1q21-1q23 by chromosomal in situ hybridization and by analysis of rodent-human somatic cell hybrids using an H2B-GL105 specific probe. The H2B-GL105 gene is paired with a functional H2A histone gene and this H2A/H2B gene pair is separated by a bidirectionally transcribed intergenic promoter region containing consensus TATA and CCAAT boxes and an OTF-1 element. These results demonstrate that cell cycle regulated and constitutively expressed histone mRNAs can be encoded by the same gene, and indicate that alternative 3' end processing may be an important mechanism for regulation of histone mRNA. Such control further increases the versatility by which cells can modulate the synthesis of replication-dependent as well as variant histone proteins during the cell cycle and at the onset of differentiation.     

Regeneration of NAD(+) cofactor by photosensitized electron transfer in an immobilized alcohol dehydrogenase system

The irradiation with visible light of a photosensitizer dye like methylene blue was used to regenerate by electron transfer the oxidized form of a pyridine nucleotide coenzyme (NAD(+)). The process has been studied on a common enzymatic reaction: ethanol oxidation by alcohol-NAD(+) oxidoreductase immobilized on polyacrylamide gel or porous glass balls. In the experimental conditions used, the initial NAD(+) recycling rates were 2.33 x 10(4) cycles/h (polyacrylamide) and 3 x 10(4) cycles/h (glass balls). A total number of 49.5 x 10(4) cycles was obtained for 13 runs of 2 h. The enzyme immobilization strongly increased its stability: after 28 days at 20 degrees C, the residual activity was 25% of the initial value.     

Inhibition of mitochondrial F1-ATPase activity by an anti-alpha subunit monoclonal antibody which modifies interactions between catalytic and regulatory sites

A monoclonal antibody, 7B3, specific to the alpha subunit of the mitochondrial ATPase-ATP synthase inhibited the rate of ATP hydrolysis by either soluble F1 or electron transport particles up to a maximum of 75%. However, 7B3 did not modify the rate of ITP hydrolysis. In addition, the apparent Km for MgATP extrapolated at high ATP concentrations had the same value in the absence as in the presence of 7B3. The antibody did not change the inactivation rate of F1-ATPase induced by dicyclohexylcarbodiimide or 4-chloro-7-nitro-2,1,3-benzoxadiazole. These observations indicate that 7B3 did not directly interfere with the catalytic sites of ATP or ITP hydrolysis. On the contrary, 7B3 modified the interaction between nucleotide sites and therefore the regulation of the rate of ATP hydrolysis. Indeed, 7B3 changed into a positive cooperativity the negative cooperativity observed when measuring the rate of ATP hydrolysis as a function of ATP concentration. 7B3 also increased the binding of ADP to F1. 7B3 prevented the rapid phase of inactivation of F1 by 5'-p-fluorosulfonylbenzoyladenosine. This phase has been correlated to the binding of 5'-p-fluorosulfonylbenzoyladenosine to regulatory sites (Di Pietro, A., Godinot, C., Martin, J. C., and Gautheron, D. C. (1979) Biochemistry 18, 1738-1745). The inhibition of ATP hydrolysis is concomitant with the binding of 1 mol of IgG or of 2 mol of Fab fragments per mol of F1. However, by further increasing the ratio Fab/F1, only 1 mol of Fab remained bound to F1 without change in inhibition of ATPase activity. All these experiments strongly support the suggestion that F1 conformational changes occurring upon binding of 7B3 to alpha subunit induce a modification of interactions between nucleotide sites. This modification would be consecutive to a change in the normal interaction between the alpha and beta subunits which is required to observe an active rate of ATP hydrolysis or synthesis. In conclusion, the use of this monoclonal antibody demonstrates for the first time in mammalian F1 the role of the conformation of the alpha subunit in the regulation of the ATPase activity.     

Bloom Syndrome and Maternal Uniparental Disomy for Chromosome 15

Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions.