Alternative development in Polystoma gallieni (Platyhelminthes,Monogenea) and life cycle evolution

Considering the addition of intermediate transmission steps during life cycle evolution, developmental plasticity, canalization forces and inherited parental effect must be invoked to explain new host colonization. Unfortunately, there is a lack of experimental procedures and relevant models to explore the adaptive value of alternative developmental phenotypes during life cycle evolution. However, within the monogeneans that are characterized by a direct life cycle, an extension of the transmission strategy of amphibian parasites has been reported within species of Polystoma and Metapolystoma (Polyopisthocotylea; Polystomatidae). In this study, we tested whether the infection success of Polystoma gallieni within tadpoles of its specific host, the Stripeless Tree Frog Hyla meridionalis, differs depending on the parental origin of the oncomiracidium. An increase in the infection success of the parasitic larvae when exposed to the same experimental conditions as their parents was expected as an adaptive pattern of non-genetic inherited information. Twice as many parasites were actually recorded from tadpoles infected with oncomiracidia hatching from eggs of the bladder parental phenotype (1.63 ± 0.82 parasites per host) than from tadpoles infected with oncomiracidia hatching from eggs of the branchial parental phenotype (0.83 ± 0.64 parasites per host). Because in natural environments the alternation of the two phenotypes is likely to occur due to the ecology of its host, the differential infection success within young tadpoles could have an adaptive value that favors the parasite transmission over time.     

Characterization of the mouse ClC-K1/Barttin chloride channel

Several Cl⁻ channels have been described in the native renal tubule, but their correspondence with ClC-K1 and ClC-K2 channels (orthologs of human ClC-Ka and ClC-Kb), which play a major role in transcellular Cl⁻ absorption in the kidney, has yet to be established. This is partly because investigation of heterologous expression has involved rat or human ClC-K models, whereas characterization of the native renal tubule has been done in mice. Here, we investigate the electrophysiological properties of mouse ClC-K1 channels heterologously expressed in Xenopus laevis oocytes and in HEK293 cells with or without their accessory Barttin subunit. Current amplitudes and plasma membrane insertion of mouse ClC-K1 were enhanced by Barttin. External basic pH or elevated calcium stimulated currents followed the anion permeability sequence Cl⁻ > Br⁻ > NO₃⁻ > I⁻. Single-channel recordings revealed a unit conductance of ~ 40 pS. Channel activity in cell-attached patches increased with membrane depolarization (voltage for half-maximal activation: ~ − 65 mV). Insertion of the V166E mutation, which introduces a glutamate in mouse ClC-K1, which is crucial for channel gating, reduced the unit conductance to ~ 20 pS. This mutation shifted the depolarizing voltage for half-maximal channel activation to ~ + 25 mV. The unit conductance and voltage dependence of wild-type and V166E ClC-K1 were not affected by Barttin. Owing to their strikingly similar properties, we propose that the ClC-K1/Barttin complex is the molecular substrate of a chloride channel previously detected in the mouse thick ascending limb (Paulais et al., J Membr. Biol, 1990, 113:253–260).     

Hormonal changes and energy substrate availability during the hibernation cycle of Syrian hamsters

Animals have to adapt to seasonal variations in food resources and temperature. Hibernation is one of the most efficient means used by animals to cope with harsh winter conditions, wherein survival is achieved through a significant decrease in energy expenditure. The hibernation period is constituted by a succession of torpor bouts (hypometabolism and decrease in body temperature) and periodic arousals (eumetabolism and euthermia). Some species feed during these periodic arousals, and thus show different metabolic adaptations to fat-storing species that fast throughout the hibernation period. Our study aims to define these metabolic adaptations, including hormone (insulin, glucagon, leptin, adiponectin, GLP-1, GiP) and metabolite (glucose, free fatty acids, triglycerides, urea) profiles together with body composition adjustments. Syrian hamsters were exposed to varied photoperiod and temperature conditions mimicking different phases of the hibernation cycle: a long photoperiod at 20 °C (LP20 group), a short photoperiod at 20 °C (SP20 group), and a short photoperiod at 8 °C (SP8). SP8 animals were sampled either at the beginning of a torpor bout (Torpor group) or at the beginning of a periodic arousal (Arousal group). We show that fat store mobilization in hamsters during torpor bouts is associated with decreased circulating levels of glucagon, insulin, leptin, and an increase in adiponectin. Refeeding during periodic arousals results in a decreased free fatty acid plasma concentration and an increase in glycemia and plasma incretin concentrations. Reduced incretin and increased adiponectin levels are therefore in accordance with the changes in nutrient availability and feeding behavior observed during the hibernation cycle of Syrian hamsters.     

A root chicory MADS box sequence and the Arabidopsis flowering repressor FLC share common features that suggest conserved function in vernalization and de‐vernalization responses

Root chicory (Cichorium intybus var. sativum) is a biennial crop, but is harvested to obtain root inulin at the end of the first growing season before flowering. However, cold temperatures may vernalize seeds or plantlets, leading to incidental early flowering, and hence understanding the molecular basis of vernalization is important. A MADS box sequence was isolated by RT‐PCR and named FLC‐LIKE1 (CiFL1) because of its phylogenetic positioning within the same clade as the floral repressor Arabidopsis FLOWERING LOCUS C (AtFLC). Moreover, over‐expression of CiFL1 in Arabidopsis caused late flowering and prevented up‐regulation of the AtFLC target FLOWERING LOCUS T by photoperiod, suggesting functional conservation between root chicory and Arabidopsis. Like AtFLC in Arabidopsis, CiFL1 was repressed during vernalization of seeds or plantlets of chicory, but repression of CiFL1 was unstable when the post‐vernalization temperature was favorable to flowering and when it de‐vernalized the plants. This instability of CiFL1 repression may be linked to the bienniality of root chicory compared with the annual lifecycle of Arabidopsis. However, re‐activation of AtFLC was also observed in Arabidopsis when a high temperature treatment was used straight after seed vernalization, eliminating the promotive effect of cold on flowering. Cold‐induced down‐regulation of a MADS box floral repressor and its re‐activation by high temperature thus appear to be conserved features of the vernalization and de‐vernalization responses in distant species.     

DNA Quality Control by a Lesion Sensor Pocket of the Xeroderma Pigmentosum Group D Helicase Subunit of TFIIH

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Highlights? Amino acid changes near the central pore of XPD confer defective excision repair ? These mutants retain DNA helicase activity when tested in an archaeal framework ? The mutants are unable to sense lesions during their ATP-driven tracking movement ? The mutants are unable to build a stable demarcation complex at DNA lesion sites     

Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity

Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and chemotherapy-induced apoptosis accounts for the generally dismal treatment outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human GBM cells exhibiting varying degrees of resistance to proapoptotic stimuli. We found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely by inhibiting big conductance Ca²⁺-activated K⁺ channel (BKCa) channel activity. Moreover, our results indicated that OP-A induced paraptosis-like cell death in GBM cells, which correlated with the vacuolization, possibly brought about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). In addition, the OP-A-induced cell death did not involve the activation of caspases. We also showed that the expression of BKCa channels colocalized with these two organelles (mitochondria and ER) was affected in this programmed cell death pathway. Thus, this study reveals a novel mechanism of action associated with the anticancer effects of OP-A, which involves the induction of paraptosis through the disruption of internal potassium ion homeostasis. Our findings offer a promising therapeutic strategy to overcome the intrinsic resistance of GBM cells to proapoptotic stimuli.     

Organizational readiness for knowledge translation in chronic care: a review of theoretical components

Background

With the persistent gaps between research and practice in healthcare systems, knowledge translation (KT) has gained significance and importance. Also, in most industrialized countries, there is an increasing emphasis on managing chronic health conditions with the best available evidence. Yet, organizations aiming to improve chronic care (CC) require an adequate level of organizational readiness (OR) for KT.Objectives: The purpose of this study is to review and synthesize the existing evidence on conceptual models/frameworks of Organizational Readiness for Change (ORC) in healthcare as the basis for the development of a comprehensive framework of OR for KT in the context of CC.

Data sources

We conducted a systematic review of the literature on OR for KT in CC using Pubmed, Embase, CINAHL, PsychINFO, Web of Sciences (SCI and SSCI), and others. Search terms included readiness; commitment and change; preparedness; willing to change; organization and administration; and health and social services.Study selection: The search was limited to studies that had been published between the starting date of each bibliographic database (e.g., 1964 for PubMed) and November 1, 2012. Only papers that refer to a theory, a theoretical component from any framework or model on OR that were applicable to the healthcare domain were considered. We analyzed data using conceptual mapping.Data extraction: Pairs of authors independently screened the published literature by reviewing their titles and abstracts. Then, the two same reviewers appraised the full text of each study independently.

Results

Overall, we found and synthesized 10 theories, theoretical models and conceptual frameworks relevant to ORC in healthcare described in 38 publications. We identified five core concepts, namely organizational dynamics, change process, innovation readiness, institutional readiness, and personal readiness. We extracted 17 dimensions and 59 sub-dimensions related to these 5 concepts.

Conclusion

Our findings provide a useful overview for researchers interested in ORC and aims to create a consensus on the core theoretical components of ORC in general and of OR for KT in CC in particular. However, more work is needed to define and validate the core elements of a framework that could help to assess OR for KT in CC.

     

The Supplementary Motor Area Exerts a Tonic Excitatory Influence on Corticospinal Projections to Phrenic Motoneurons in Awake Humans

Introduction

In humans, cortical mechanisms can interfere with autonomic breathing. Respiratory-related activation of the supplementary motor area (SMA) has been documented during voluntary breathing and in response to inspiratory constraints. The SMA could therefore participate in the increased resting state of the respiratory motor system during wake (i.e. "wakefulness drive to breathe").

Methods

The SMA was conditioned by continuous theta burst magnetic stimulation (cTBS, inhibitory) and 5 Hz conventional rTMS (5 Hz, excitatory). The ensuing effects were described in terms of the diaphragm motor evoked response (DiMEPs) to single-pulse transcranial magnetic stimulation over the motor cortex. DiMEPs were recorded at baseline, and at 3 time-points ("post1", "post2", "post3") up to 15 minutes following conditioning of the SMA.

Results

cTBS reduced the amplitude of DiMEPs from 327.5±159.8 µV at baseline to 243.3±118.7 µV, 217.8±102.9 µV and 240.6±123.9 µV at post 1, post 2 and post 3, respectively (F = 6.341, p = 0.002). 5 Hz conditioning increased the amplitude of DiMEPs from 184.7±96.5 µV at baseline to 270.7±135.4 µV at post 3 (F = 4.844, p = 0.009).

Conclusions

The corticospinal pathway to the diaphragm can be modulated in both directions by conditioning the SMA. This suggests that the baseline respiratory activity of the SMA represents an equipoise from which it is possible to move in either direction. The resting corticofugal outflow from the SMA to phrenic motoneurones that this study evidences could putatively contribute to the wakefulness drive to breathe.