Olfactory cue use by three-spined sticklebacks foraging in turbid water: prey detection or prey location?

Foraging, when senses are limited to olfaction, is composed of two distinct stages: the detection of prey and the location of prey. While specialist olfactory foragers are able to locate prey using olfactory cues alone, this may not be the case for foragers that rely primarily on vision. Visual predators in aquatic systems may be faced with poor visual conditions such as natural or human-induced turbidity. The ability of visual predators to compensate for poor visual conditions by using other senses is not well understood, although it is widely accepted that primarily visual fish, such as three-spined sticklebacks, Gasterosteus aculeatus, can detect and use olfactory cues for a range of purposes. We investigated the ability of sticklebacks to detect the presence of prey and to locate prey precisely, using olfaction, in clear and turbid (two levels) water. When provided with only a visual cue, or only an olfactory cue, sticklebacks showed a similar ability to detect prey, but a combination of these cues improved their performance. In open-arena foraging trials, a dispersed olfactory cue added to the water (masking cues from the prey) improved foraging success, contrary to our expectations, whereas activity levels and swimming speed did not change as a result of olfactory cue availability. We suggest that olfaction functions to allow visual predators to detect rather than locate prey and that olfactory cues have an appetitive effect, enhancing motivation to forage

Prey aggregation is an effective olfactory predator avoidance strategy

Predator–prey interactions have a major effect on species abundance and diversity, and aggregation is a well-known anti-predator behaviour. For immobile prey, the effectiveness of aggregation depends on two conditions: (a) the inability of the predator to consume all prey in a group and (b) detection of a single large group not being proportionally easier than that of several small groups. How prey aggregation influences predation rates when visual cues are restricted, such as in turbid water, has not been thoroughly investigated. We carried out foraging (predation) experiments using a fish predator and (dead) chironomid larvae as prey in both laboratory and field settings. In the laboratory, a reduction in visual cue availability (in turbid water) led to a delay in the location of aggregated prey compared to when visual cues were available. Aggregated prey suffered high mortality once discovered, leading to better survival of dispersed prey in the longer term. We attribute this to the inability of the dead prey to take evasive action. In the field (where prey were placed in feeding stations that allowed transmission of olfactory but not visual cues), aggregated (large groups) and semi-dispersed prey survived for longer than dispersed prey—including long termsurvival. Together, our results indicate that similar to systems where predators hunt using vision, aggregation is an effective anti-predator behaviour for prey avoiding olfactory predators

Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC subversion induces up-regulation of PKC II expression in B lymphocytes

Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKCα leads to an up-regulation of PKCβII expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKCβ inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKCβII in chronic lymphocytic leukemia-like disease progression and suggest a role for PKCα subversion in creating permissive conditions for leukemogenesis

Should sex ratio distorting parasites abandon horizontal transmission?

BACKGROUND: Sex-ratio distorting parasites are of interest due to their effects upon host population dynamics and their potential to influence the evolution of host sex determination systems. In theory, the ability to distort host sex-ratios allows a parasite with efficient vertical (hereditary) transmission to dispense completely with horizontal (infectious) transmission. However, recent empirical studies indicate that some sex-ratio distorting parasites have retained the capability for horizontal transmission. RESULTS: Numerical simulations using biologically realistic parameters suggest that a feminising parasite is only likely to lose the capability for horizontal transmission if its host occurs at low density and/or has a male-biased primary sex ratio. It is also demonstrated that even a small amount of horizontal transmission can allow multiple feminising parasites to coexist within a single host population. Finally it is shown that, by boosting its host's rate of population growth, a feminising parasite can increase its own horizontal transmission and allow the invasion of other, more virulent parasites. CONCLUSIONS: The prediction that sex-ratio distorting parasites are likely to retain a degree of horizontal transmission has important implications for the epidemiology and host-parasite interactions of these organisms. It may also explain the frequent co-occurrence of several sex-ratio distorting parasite species in nature

mTORC1 activity is essential for erythropoiesis and B cell lineage commitment

Mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that mediates phosphoinositide-3-kinase (PI3K)/AKT signalling. This pathway is involved in a plethora of cellular functions including protein and lipid synthesis, cell migration, cell proliferation and apoptosis. In this study, we proposed to delineate the role of mTORC1 in haemopoietic lineage commitment using knock out (KO) mouse and cell line models. Mx1-cre and Vav-cre expression systems were used to specifically target Raptorfl/fl (mTORC1), either in all tissues upon poly(I:C) inoculation, or specifically in haemopoietic stem cells, respectively. Assessment of the role of mTORC1 during the early stages of development in Vav-cre+Raptorfl/fl mice, revealed that these mice do not survive post birth due to aberrations in erythropoiesis resulting from an arrest in development at the megakaryocyte-erythrocyte progenitor stage. Furthermore, Raptor-deficient mice exhibited a block in B cell lineage commitment. The essential role of Raptor (mTORC1) in erythrocyte and B lineage commitment was confirmed in adult Mx1-cre+Raptorfl/fl mice upon cre-recombinase induction. These studies were supported by results showing that the expression of key lineage commitment regulators, GATA1, GATA2 and PAX5 were dysregulated in the absence of mTORC1-mediated signals. The regulatory role of mTOR during erythropoiesis was confirmed in vitro by demonstrating a reduction of K562 cell differentiation towards RBCs in the presence of established mTOR inhibitors. While mTORC1 plays a fundamental role in promoting RBC development, we showed that mTORC2 has an opposing role, as Rictor-deficient progenitor cells exhibited an elevation in RBC colony formation ex vivo. Collectively, our data demonstrate a critical role played by mTORC1 in regulating the haemopoietic cell lineage commitment

Determinants of parasite distribution in Arctic charr populations: catchment structure versus dispersal potential

Parasite distribution patterns in lotic catchments are driven by the combined influences of unidirectional water flow and the mobility of the most mobile host. However, the importance of such drivers in catchments dominated by lentic habitats are poorly understood. We examined parasite populations of Arctic charr Salvelinus alpinus from a series of linear-connected lakes in northern Norway to assess the generality of lotic-derived catchment-scale parasite assemblage patterns. Our results demonstrated that the abundance of most parasite taxa increased from the upper to lower catchment. Allogenic taxa (piscivorous birds as final host) were present throughout the entire catchment, whereas their autogenic counterparts (charr as final hosts) demonstrated restricted distributions, thus supporting the theory that the mobility of the most mobile host determines taxa-specific parasite distribution patterns. Overall, catchmentwide parasite abundance and distribution patterns in this lentic-dominated system were in accordance with those reported for lotic systems. Additionally, our study highlighted that upper catchment regions may be inadequate reservoirs to facilitate recolonization of parasite communities in the event of downstream environmental perturbations

Determinants of parasite distribution in Arctic charr populations: catchment structure versus dispersal potential

Parasite distribution patterns in lotic catchments are driven by the combined influences of unidirectional water flow and the mobility of the most mobile host. However, the importance of such drivers in catchments dominated by lentic habitats are poorly understood. We examined parasite populations of Arctic charr Salvelinus alpinus from a series of linear-connected lakes in northern Norway to assess the generality of lotic-derived catchment-scale parasite assemblage patterns. Our results demonstrated that the abundance of most parasite taxa increased from the upper to lower catchment. Allogenic taxa (piscivorous birds as final host) were present throughout the entire catchment, whereas their autogenic counterparts (charr as final hosts) demonstrated restricted distributions, thus supporting the theory that the mobility of the most mobile host determines taxa-specific parasite distribution patterns. Overall, catchmentwide parasite abundance and distribution patterns in this lentic-dominated system were in accordance with those reported for lotic systems. Additionally, our study highlighted that upper catchment regions may be inadequate reservoirs to facilitate recolonization of parasite communities in the event of downstream environmental perturbations

Economic considerations for moving beyond the Kato-Katz technique for diagnosing intestinal parasites as we move towards elimination

While the need for more sensitive diagnostics for intestinal helminths is well known, the cost of developing and implementing new tests is considered relatively high compared to the Kato-Katz technique. Here, we review the reported costs of performing the Kato-Katz technique. We also outline several economic arguments we believe highlight the need for further investment in alternative diagnostics, and considerations that should be made when comparing their costs. In our opinion, we highlight that, without new diagnostic methods, it will be difficult for policy makers to make the most cost-effective decisions and that the potentially higher unit costs of new methods can be outweighed by the long-term programmatic benefits they have (such as the ability to detect the interruption of transmission)

Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells

Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second-and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival(1). However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs)(2-4). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically(5,6). Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner(7), we searched for such vulnerabilities in CML LSCs. We performed metabolic analyses on both stem cell-enriched (CD34(+) and CD34(+)CD38(-)) and differentiated (CD34(-)) cells derived from individuals with CML, and we compared the signature of these cells with that of their normal counterparts. Through combination of stable isotope-assisted metabolomics with functional assays, we demonstrate that primitive CML cells rely on upregulated oxidative metabolism for their survival. We also show that combination treatment with imatinib and tigecycline, an antibiotic that inhibits mitochondrial protein translation, selectively eradicates CML LSCs both in vitro and in a xenotransplantation model of human CML. Our findings provide a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease