A non-conducting role of the Cav1.4 Ca2+ channel drives homeostatic plasticity at the cone photoreceptor synapse.

In congenital stationary night blindness type 2 (CSNB2)-a disorder involving the Cav1.4 (L-type) Ca2+ channel-visual impairment is mild considering that Cav1.4 mediates synaptic release from rod and cone photoreceptors. Here, we addressed this conundrum using a Cav1.4 knockout (KO) mouse and a knock-in (G369i KI) mouse expressing a non-conducting Cav1.4. Surprisingly, Cav3 (T-type) Ca2+ currents were detected in cones of G369i KI mice and Cav1.4 KO mice but not in cones of wild-type mouse, ground squirrel, and macaque retina. Whereas Cav1.4 KO mice are blind, G369i KI mice exhibit normal photopic (i.e., cone-mediated) visual behavior. Cone synapses, which fail to form in Cav1.4 KO mice, are present, albeit enlarged, and with some errors in postsynaptic wiring in G369i KI mice. While Cav1.4 KO mice lack evidence of cone synaptic responses, electrophysiological recordings in G369i KI mice revealed nominal transmission from cones to horizontal cells and bipolar cells. In CSNB2, we propose that Cav3 channels maintain cone synaptic output provided that the nonconducting role of Cav1.4 in cone synaptogenesis remains intact. Our findings reveal an unexpected form of homeostatic plasticity that relies on a non-canonical role of an ion channel.

A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse.

Synapses are fundamental information processing units that rely on voltage-gated Ca2+ (Cav) channels to trigger Ca2+-dependent neurotransmitter release. Cav channels also play Ca2+-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Cav1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Cav1.4, we report that the Cav1.4 protein, but not its Ca2+ conductance, is required for the molecular assembly of rod synapses; however, Cav1.4 Ca2+ signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Cav channels serve both as organizers of synaptic building blocks and as sources of Ca2+ ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.

An Assessment of Climate Induced Increase in Soil Water Availability for Soil Bacterial Communities Exposed to Long-Term Differential Phosphorus Fertilization.

The fate of future food productivity depends primarily upon the health of soil used for cultivation. For Atlantic Europe, increased precipitation is predicted during both winter and summer months. Interactions between climate change and the fertilization of land used for agriculture are therefore vital to understand. This is particularly relevant for inorganic phosphorus (P) fertilization, which already suffers from resource and sustainability issues. The soil microbiota are a key indicator of soil health and their functioning is critical to plant productivity, playing an important role in nutrient acquisition, particularly when plant available nutrients are limited. A multifactorial, mesocosm study was established to assess the effects of increased soil water availability and inorganic P fertilization, on spring wheat biomass, soil enzymatic activity (dehydrogenase and acid phosphomonoesterase) and soil bacterial community assemblages. Our results highlight the significance of the spring wheat rhizosphere in shaping soil bacterial community assemblages and specific taxa under a moderate soil water content (60%), which was diminished under a higher level of soil water availability (80%). In addition, an interaction between soil water availability and plant presence overrode a long-term bacterial sensitivity to inorganic P fertilization. Together this may have implications for developing sustainable P mobilization through the use of the soil microbiota in future. Spring wheat biomass grown under the higher soil water regime (80%) was reduced compared to the constant water regime (60%) and a reduction in yield could be exacerbated in the future when grown in cultivated soil that have been fertilized with inorganic P. The potential feedback mechanisms for this need now need exploration to understand how future management of crop productivity may be impacted.

Reduced-intensity conditioning allogeneic transplantation after salvage treatment with DT-PACE in myeloma patients relapsing early after autologous transplant.

OBJECTIVE: In this retrospective single-centre study, we have looked into the transplant outcomes(overall survival OS, progression-free survival PFS, GvHD) and the role of chimerism, DLI and pretransplant characteristics in patients who had a suboptimal response (<12 months) to an autologous stem cell transplant for myeloma and underwent an alemtuzumab T-cell depleted reduced-intensity allograft(RIC). METHODS: Twenty-four patients were salvaged with two cycles of DT-PACE and received a RIC transplant with fludarabine, melphalan and alemtuzumab. All the patients received PBSC grafts, eight patients had a sibling donor, and 16 had a graft from a fully matched unrelated donor. The median follow-up was 65.3 months (6-132 months). RESULTS: The median overall survival was 55.4 months. DLI administration was associated with a trend towards better overall survival (P=.05). Disease status at allo-HCT, PR or VGPR, ISS score and CMV serostatus was not significant predictors of OS and PFS. Full donor whole blood chimerism (≥98%) at 3 months post-transplant was associated with PFS (P=.04) but did not have a significant impact on OS(P=.45). CONCLUSION: Reduced-intensity alemtuzumab-conditioned allograft for myeloma after DT-PACE salvage chemotherapy is an efficient and low toxicity treatment for those who had a suboptimal response postautologous stem cell transplant for myeloma.

Increasing phosphorus supply is not the mechanism by which arbuscular mycorrhiza increase attractiveness of bean (Vicia faba) to aphids.

Arbuscular mycorrhizal (AM) fungi, important plant mutualists, provide plants with nutrients such as phosphorus (P) in return for carbon. AM fungi also enhance the attractiveness of plants to aphids via effects on emissions of plant volatiles used in aphid host location. We tested whether increased P uptake by plants is the mechanism through which AM fungi alter the volatile profile of plants and aphid behavioural responses by manipulating the availability of P and AM fungi to broad beans (Vicia faba L.) in a multi-factorial design. If AM fungi affect plant volatiles only via increased P acquisition, we predicted that the emission of volatiles and the attractiveness of mycorrhizal beans to aphids would be similar to those of non-mycorrhizal beans supplied with additional P. AM fungi and P addition increased leaf P concentrations by 40 and 24%, respectively. The production of naphthalene was less in mycorrhizal plants, regardless of P addition. By contrast, production of (S)-linalool, (E)-caryophyllene and (R)-germacrene D was less in plants colonized by AM fungi but only in the absence of P additions. The attractiveness of plants to pea aphids (Acyrthosiphon pisum Harris) was positively affected by AM fungi and correlated with the extent of root colonization; however, attractiveness was neither affected by P treatment nor correlated with leaf P concentration. These findings suggest that increased P uptake is not the main mechanism by which mycorrhiza increase the attractiveness of plants to aphids. Instead, the mechanism is likely to operate via AM fungi-induced plant systemic signalling.

Cognitive control in children with ADHD-C: how efficient are they?

The literature on children with attention deficit/hyperactivity disorder, combined type (ADHD-C), is currently inconclusive as to the nature of deficits in two forms of cognitive control - interference control and response selection (Nigg, 2006). This paper examined the performance of children with ADHD-C on interference control and response selection conflict tasks that required both speed and accuracy. The data was analyzed utilizing a new efficiency method to more effectively analyze overall responses. Both interference control and response selection conditions were combined within tasks allowing for a closer comparison of how children with ADHD-C perform on these specific types of cognitive control. Computerized tasks were administered to 62 boys, ages 7 to 12 (31 controls, 31 ADHD-C). Results revealed deficits in efficient performance for children with ADHD-C on interference control tasks and response selection tasks hypothesized to involve high cognitive control demand. These results highlight the utility of analyzing efficiency data to identify deficits in performance for children with ADHD-C and to foster an increased understanding of cognitive control functioning in this clinical population.

Working memory in school-aged children with attention-deficit/hyperactivity disorder combined type: are deficits modality specific and are they independent of impaired inhibitory control?

This study examines differences between children with attention-deficit/ hyperactivity disorder combined type (ADHD-C) and normal controls on verbal and visuospatial working-memory (WM) tasks. The extent to which WM deficits in children with ADHD-C are independent of impaired inhibitory control was also examined. Two groups of 7- to 12-year-old boys participated in this study. The first group included 31 boys diagnosed with ADHD-C, and the second group included 34 boys without ADHD. Various verbal and visuospatial WM tasks and two inhibitory control tasks--prepotent response inhibition and interference control--were used. Overall, our results suggest impaired verbal and visuospatial WM processes in children with ADHD-C, as well as a lower level of performance on prepotent response inhibition. WM deficits in ADHD have previously been suggested to be particularly salient in the spatial domain; our results instead showed the largest effect for a verbal WM task thought to put heavy load on the executive or attentional control component of the WM system. An interpretation of this finding is that it is variation in terms of difficulty level or load on the executive WM processes, rather than variation in modality (verbal versus visuospatial), that is important in demonstrating WM deficits in ADHD-C. Finally, findings from logistic regression analyses showed that deficits in WM and inhibitory control seem to be semi-independent in children with ADHD-C, at least with regard to the elementary school age.