Copepod flow modes and modulation: a modelling study of the water currents produced by an unsteadily swimming copepod

Video observation has shown that feeding-current-producing calanoid copepods modulate their feeding currents by displaying a sequence of different swimming behaviours during a time period of up to tens of seconds. In order to understand the feeding-current modulation process, we numerically modelled the steady feeding currents for different modes of observed copepod motion behaviours (i.e. free sinking, partial sinking, hovering, vertical swimming upward and horizontal swimming backward or forward). Based on observational data, we also reproduced numerically a modulated feeding current associated with an unsteadily swimming copepod. We found that: (i) by changing its propulsive force, a copepod can switch between different swimming behaviours, leading to completely different flow-field patterns in self-generated surrounding flow; (ii) by exerting a time-varying propulsive force, a copepod can modulate temporally the basic flow modes to create an unsteady feeding current which manipulates precisely the trajectories of entrained food particles over a long time period; (iii) the modulation process may be energetically more efficient than exerting a constant propulsive force onto water to create a constant feeding current of a wider entrainment range. A probable reason is that the modulated unsteady flow entrains those water parcels containing food particles and leaves behind those without valuable food in them.     

Otolith crystals (in Carapidae): growth and habit

The biomineralization of otoliths results mainly from the release of soluble Ca(2+), which is in turn precipitated as CaCO(3) crystals. In some Carapidae, sagittae sections have been shown to reveal a three-dimensional asymmetry with a nucleus close to the sulcal side, an unusual position. This study seeks to understand otolith formation in Carapus boraborensis. The unusual shape of the otolith is partly explained by the distribution of the epithelium cells, and particularly the sensory epithelium. Experimental evidence shows for the first time that aragonite growth takes place along the c-axis. These aragonite needles present two different habits. On the sulcal side is found the acicular form resulting from rapid growth during a short period of time. On the anti-sulcal side, the prismatic form seen there is due to a slower growth speed over longer periods. The otolith surface was observed each hour during a period of 24h in fishes reared in similar conditions. This allowed for the first time the direct observation on the otolith surface of the deposition of the two layers (L-zone and D-zone). In C. boraborensis, the organic-rich layer (D-zone) develops during the day, whereas the CaCO(3) layer (L-zone) seems to be deposited during the night.     

The effect of five weeks of Tribulus terrestris supplementation on muscle strength and body composition during preseason training in elite rugby league players

Tribulus terrestris is an herbal nutritional supplement that is promoted to produce large gains in strength and lean muscle mass in 5-28 days (15, 18). Although some manufacturers claim T. terrestris will not lead to a positive drug test, others have suggested that T. terrestris may increase the urinary testosterone/epitestosterone (T/E) ratio, which may place athletes at risk of a positive drug test. The purpose of the study was to determine the effect of T. terrestris on strength, fat free mass, and the urinary T/E ratio during 5 weeks of preseason training in elite rugby league players. Twenty-two Australian elite male rugby league players (mean +/- SD; age = 19.8 +/- 2.9 years; weight = 88.0 +/- 9.5 kg) were match-paired and randomly assigned in a double-blind manner to either a T. terrestris (n = 11) or placebo (n = 11) group. All subjects performed structured heavy resistance training as part of the club's preseason preparations. A T. terrestris extract (450 mg.d(-1)) or placebo capsules were consumed once daily for 5 weeks. Muscular strength, body composition, and the urinary T/E ratio were monitored prior to and after supplementation. After 5 weeks of training, strength and fat free mass increased significantly without any between-group differences. No between-group differences were noted in the urinary T/E ratio. It was concluded that T. terrestris did not produce the large gains in strength or lean muscle mass that many manufacturers claim can be experienced within 5-28 days. Furthermore, T. terrestris did not alter the urinary T/E ratio and would not place an athlete at risk of testing positive based on the World Anti-Doping Agency's urinary T/E ratio limit of 4:1.     

Induction of tolerance to human arylsulfatase A in a mouse model of metachromatic leukodystrophy

A deficiency of arylsulfatase A (ASA) causes metachromatic leukodystrophy (MLD), a lysosomal storage disorder characterized by accumulation of sulfatide, a severe neurological phenotype and early death. The efficacy of enzyme replacement therapy (ERT) has previously been determined in ASA knockout (ASA-/-) mice representing the only available animal model for MLD. Repeated intravenous injection of human ASA (hASA) improved the nervous system pathology and function, but also elicited a progressive humoral immune response leading to treatment resistance, anaphylactic reactions, and high mortality. In contrast to ASA-/- mice, most MLD patients express mutant hASA which may entail immunological tolerance to substituted wildtype hASA and thus protect from immunological complications. To test this notion, a cysteine-to-serine substitution was introduced into the active site of the hASA and the resulting inactive hASA-C69S variant was constitutively expressed in ASA-/- mice. Mice with sub-to supranormal levels of mutant hASA expression were analyzed. All mice, including those showing transgene expression below the limit of detection, were immunologically unresponsive to injected hASA. More than 100-fold overexpression did not induce an overt new phenotype except occasional intralysosomal deposition of minor amounts of glycogen in hepatocytes. Furthermore, long-term, low-dose ERT reduced sulfatide storage in peripheral tissues and the central nervous system indicating that high levels of extracellular mutant hASA do not prevent cellular uptake and lysosomal targeting of substituted wildtype hASA. Due to the tolerance to hASA and maintenance of the MLD-like phenotype, the novel transgenic strain may be particularly advantageous to assess the benefit and risk of long-term ERT.     

13CO2/12CO2 exchange fluxes in a clamp‐on leaf cuvette: disentangling artefacts and flux components

Leaks and isotopic disequilibria represent potential errors and artefacts during combined measurements of gas exchange and carbon isotope discrimination (Δ). This paper presents new protocols to quantify, minimize, and correct such phenomena. We performed experiments with gradients of CO₂ concentration (up to ±250 μmol mol^?1) and δ¹³C_CO2 (34‰), between a clamp‐on leaf cuvette (LI‐6400) and surrounding air, to assess (1) leak coefficients for CO₂, ¹²CO₂, and ¹³CO₂ with the empty cuvette and with intact leaves of Holcus lanatus (C₃) or Sorghum bicolor (C₄) in the cuvette; and (2) isotopic disequilibria between net photosynthesis and dark respiration in light. Leak coefficients were virtually identical for ¹²CO₂ and ¹³CO₂, but ～8 times higher with leaves in the cuvette. Leaks generated errors on Δ up to 6‰ for H. lanatus and 2‰ for S. bicolor in full light; isotopic disequilibria produced similar variation of Δ. Leak errors in Δ in darkness were much larger due to small biological : leak flux ratios. Leak artefacts were fully corrected with leak coefficients determined on the same leaves as Δ measurements. Analysis of isotopic disequilibria enabled partitioning of net photosynthesis and dark respiration, and indicated inhibitions of dark respiration in full light (H. lanatus: 14%, S. bicolor: 58%).     

Activation of the PI3K pathway increases TLR-induced TNF-α and IL-6 but reduces IL-1β production in mast cells

Recognition of bacterial constituents by mast cells (MCs) is dependent on the presence of pattern recognition receptors, such as Toll-like receptors (TLRs). The final cellular response, however, depends on the influence of multiple environmental factors. In the current study we tested the hypothesis that the PI3K-activating ligands insulin-like growth factor-1 (IGF-1), insulin, antigen, and Steel Factor (SF) are able to modulate the TLR4-mediated production of proinflammatory cytokines in murine MCs. Costimulation with any of these ligands caused increased LPS-triggered secretion of IL-6 and TNF-α, but attenuated the production of IL-1β, though all three cytokines were produced in an NFκB-dependent manner. The pan-specific PI3K-inhibitor Wortmannin reverted the altered production of these cytokines. In agreement, MCs deficient for SHIP1, a negative regulator of the PI3K pathway, showed augmented secretion of IL-6/TNF-α and reduced production of IL-1β in response to LPS alone. The differential effects of IGF-1 on TLR4-mediated cytokine production were also observed in the context of TLR2 and IL-33 receptor-mediated MC activation. Importantly, these effects were seen in both bone marrow-derived and peritoneal MCs, suggesting general relevance for MCs. Using pharmacological and genetic tools, we could show that the p110δ isoform of PI3K is strongly implicated in SF-triggered suppression of LPS-induced IL-1β production. Costimulation with antigen was affected to a lesser extent. In conclusion, NFκB-dependent production of proinflammatory cytokines in MCs is differentially controlled by PI3K-activating ligand/receptor systems.     

The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil

Mustard oil (MO) is a plant-derived irritant that has been extensively used in experimental models to induce pain and inflammation. The noxious effects of MO are currently ascribed to specific activation of the cation channel TRPA1 in nociceptive neurons. In contrast to this view, we show here that the capsaicin receptor TRPV1 has a surprisingly large contribution to aversive and pain responses and visceral irritation induced by MO. Furthermore, we found that this can be explained by previously unknown properties of this compound. First, MO has a bimodal effect on TRPA1, producing current inhibition at millimolar concentrations. Second, it directly and stably activates mouse and human recombinant TRPV1, as well as TRPV1 channels in mouse sensory neurons. Finally, physiological temperatures enhance MO-induced TRPV1 stimulation. Our results refute the dogma that TRPA1 is the sole nocisensor for MO and motivate a revision of the putative roles of these channels in models of MO-induced pain and inflammation. We propose that TRPV1 has a generalized role in the detection of irritant botanical defensive traits and in the coevolution of multiple mammalian and plant species.     

Regulation of NF-κB signaling by caspases and MALT1 paracaspase

Caspases are intracellular proteases that are best known for their function in apoptosis signaling. It has become evident that many caspases also function in other signaling pathways that propagate cell proliferation and inflammation, but studies on the inflammatory function of caspases have mainly been limited to caspase-1-mediated cytokine processing. Emerging evidence, however, indicates an important contribution of caspases as mediators or regulators of nuclear factor-κB (NF-κB) signaling, which plays a key role in inflammation and immunity. Much still needs to be learned about the mechanisms that govern the activation and regulation of NF-κB by caspases, and this review provides an update of this area. Whereas apoptosis signaling is dependent on the catalytic activity of caspases, they mainly act as scaffolding platforms for other signaling proteins in the case of NF-κB signaling. Caspase proteolytic activity, however, counteracts the pro-survival function of NF-κB by cleaving specific signaling molecules. A striking exception is the paracaspase mucosa-associated lymphoid tissue 1 (MALT1), whose adaptor and proteolytic activity are both needed to initiate a full blown NF-κB response in antigen-stimulated lymphocytes. Understanding the role of caspases and MALT1 in the regulation of NF-κB signaling is of high interest for therapeutic immunomodulation.