Dopamine D3 receptor knockout mice exhibit increased hippocampal cAMP response element binding protein (CREB) following acquisition of passive avoidance memory

The dopamine D3 (D3R) receptor seems to be implicated in synaptic plasticity and memory-related processes as identified by several pharmacological and behavioral approaches (Laszy et al., 2005; Swant 2008). In a previous study we have shown that D3Rs mediate an inhibitory effect on learning, since D3R knockout (D3-/-) mice display enhanced cognitive performance in the single trial step-through passive avoidance task (PA) as compared to WTs (Micale et al., 2010; D’Amico et al., 2013). Formation of new memories is known to require de novo synthesis of proteins related to synaptic function, possibly through the activation of a number of signaling pathways including the mitogen-activated protein kinases (MAPKs), protein kinase B (namely Akt) and the activation of nuclear transcription factors such as the cAMP response element binding protein (CREB). However, no clear indications have yet been provided regarding the specific involvement of D3Rs in the activation of these signaling cascades after acquisition of PA. Therefore, in the present study we assessed whether activity/phosphorylation levels of several MAPKs, Akt and CREB were differentially affected by PA in both wild-type (WT) and D3-/- mice. Animals were divided into four groups: naive, unconditioned stimulus trained (USTA), conditioned stimulus trained (CSTA) and conditioned (CA) animals. Phosphorylation of MAPKs, including extracellular signal-regulated kinase 1/2 (ERK 1/2), c-Jun-N-terminal kinase (JNK) and p38, as well as of Akt and CREB were assessed by immunoblotting and immunohistochemical analyses. Results showed that acquisition of PA induced a significant increase in hippocampal pCREB levels both in WT and D3-/- mice. However, the extent of PA-driven increase in pCREB levels was significantly higher in mice lacking D3Rs. Similarly, hippocampal pERK 1/2 were further augmented in D3-/- mice subjected to PA as compared to trained WTs. JNK and p38 phosphorylation was not affected neither by PA nor by genetic background. Finally, a significantly increased Akt activation was observed only when comparing naïve WT and D3-/- mice, but not in response to PA acquisition. This result suggests that the Akt signaling cascade is influenced by the absence of the receptor, but only under basal conditions. In conclusion, the data here presented supports the notion that D3Rs might modulate CREB phosphorylation after acquisition of PA, probably via activation of the ERK signaling pathway

Highly Variable Taxa-specific Coral Bleaching Responses to Thermal Stresses

Complex histories of chronic and acute sea surface temperature (SST) stresses are expected to trigger taxon- and location-specific responses that will ultimately lead to novel coral communities. The 2016 El Niño-Southern Oscillation provided an opportunity to examine large- scale and recent environmental histories on emerging patterns in 226 coral communities distrib- uted across 12 countries from East Africa to Fiji. Six main coral communities were identified that largely varied across a gradient of Acropora to massive Porites dominance. Bleaching intensity was taxon-specific and was associated with complex interactions among the 20 environmental variables that we examined. Coral community structure was better aligned with the historical temperature patterns between 1985 and 2015 than the 2016 extreme temperature event. Addi- tionally, bleaching responses observed during 2016 differed from historical reports during past warm years. Consequently, coral communities present in 2016 are likely to have been reorganized by both long-term community change and acclimation mechanisms. For example, less disturbed sites with cooler baseline temperatures, higher mean historical SST background variability, and infrequent extreme warm temperature stresses were associated with Acropora-dominated communities, while more disturbed sites with lower historical SST background variability and frequent acute warm stress were dominated by stress-resistant massive Porites corals. Overall, the combination of taxon-specific responses, community-level reorganization over time, geographic variation, and multiple environmental stressors suggest complex responses and a diversity of future coral communities that can help contextualize management priorities and activities

A simple model to evaluate ice melt over the ablation area of glaciers in the Central Karakoram National Park, Pakistan

This study provides an estimate of fresh water derived from ice melt for the ablation areas of glaciers in the Central Karakoram National Park (CKNP), Pakistan. In the CKNP there are ~700 glaciers, covering ~4600 km2, with widespread debris cover (518 km2). To assess meltwater volume we applied a distributed model able to describe both debris-covered and debris-free ice ablation. The model was calibrated using data collected in the field in the CKNP area and validated by comparison with ablation data collected in the field, independent of the data used in building the model. During 23 July\u20139 August 2011, the mean model-estimated ablation in the CKNP was 0.024 m w.e./ d in debris covered areas and 0.037 m w.e./ d in debris-free areas. We found a mean error of +0.01 m w.e. (corresponding to 2%) and a root-mean-square error equal to 0.09 m w.e. (17%). According to our model, the ablation areas of all the glaciers in the CKNP produced a water volume of 1.963 km3 during the study period. Finally, we performed several sensitivity tests for assessing the impact of the input data variations

Large Geographic Variability in the Resistance of Corals to Thermal Stress

Aim: Predictions for the future of coral reefs are largely based on thermal exposure and poorly account for potential geographic variation in biological sensitivity to ther- mal stress. Without accounting for complex sensitivity responses, simple climate ex- posure models and associated predictions may lead to poor estimates of future coral survival and lead to policies that fail to identify and implement the most appropri- ate interventions. To begin filling this gap, we evaluated a number of attributes of coral taxa and communities that are predicted to influence coral resistance to thermal stress over a large geographic range. Location: Western Indo-Pacific and Central Indo-Pacific Ocean Realms. Major taxa studied: Zooxanthellate Scleractinia – hard corals. Methods: We evaluated the geographic variability of coral resistance to thermal stress as the ratio of thermal exposure and sensitivity in 12 countries during the 2016 global-bleaching event. Thermal exposure was estimated by two metrics: (a) histori- cal excess summer heat (cumulative thermal anomaly, CTA), and (b) a multivariate index of sea-surface temperature (SST), light, and water flow (climate exposure, CE). Sensitivity was estimated for 226 sites using coordinated bleaching observations and underwater surveys of coral communities. We then evaluated coral resistance to ther- mal stress using 48 generalized linear mixed models (GLMMs) to compare the poten- tial influences of geography, historical SST variation, coral cover and coral richness. Results: Geographic faunal provinces and ecoregions were the strongest predic- tors of coral resistance to thermal stress, with sites in the Australian, Indonesian and Fiji-Caroline Islands coral provinces having higher resistance to thermal stress than Africa-India and Japan-Vietnam provinces. Ecoregions also showed strong gradients in resistance with highest resistance to thermal stress in the western Pacific and Coral Triangle and lower resistance in the surrounding ecoregions. A more detailed evaluation of Coral Triangle and non-Coral Triangle sites found higher resistance to thermal stress within the Coral Triangle, associated with c. 2.5 times more recent historical thermal anomalies and more centralized, warmer, and cool-water skew SST distributions, than in non-Coral Triangle sites. Our findings identify the importance of environmental history and geographic context in future predictions of bleaching, and identify some potential drivers of coral resistance to thermal stress. Main conclusions: Simple threshold models of heat stress and coral acclimation are commonly used to predict the future of coral reefs. Here and elsewhere we show that large-scale responses of coral communities to heat stress are geographically variable and associated with differential environmental stresses and histories

Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort

BACKGROUND The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.Peer reviewe

Clinical and molecular epidemiology of methicillin-resistant Staphylococcus aureus in New Zealand: rapid emergence of sequence type 5 (ST5)-SCCmec-IV as the dominant community-associated MRSA clone.

The predominant community-associated MRSA strains vary between geographic settings, with ST8-IV USA300 being the commonest clone in North America, and the ST30-IV Southwest Pacific clone established as the dominant clone in New Zealand for the past two decades. Moreover, distinct epidemiological risk factors have been described for colonisation and/or infection with CA-MRSA strains, although these associations have not previously been characterized in New Zealand. Based on data from the annual New Zealand MRSA survey, we sought to describe the clinical and molecular epidemiology of MRSA in New Zealand. All non-duplicate clinical MRSA isolates from New Zealand diagnostic laboratories collected as part of the annual MRSA survey were included. Demographic data was collected for all patients, including age, gender, ethnicity, social deprivation index and hospitalization history. MRSA was isolated from clinical specimens from 3,323 patients during the 2005 to 2011 annual surveys. There were marked ethnic differences, with MRSA isolation rates significantly higher in Māori and Pacific Peoples. Over the study period, there was a significant increase in CA-MRSA, and a previously unidentified PVL-negative ST5-IV spa t002 clone replaced the PVL-positive ST30-IV Southwest Pacific clone as the dominant CA-MRSA clone. Of particular concern was the finding of several successful and virulent MRSA clones from other geographic settings, including ST93-IV (Queensland CA-MRSA), ST8-IV (USA300) and ST772-V (Bengal Bay MRSA). Ongoing molecular surveillance is essential to prevent these MRSA strains becoming endemic in the New Zealand healthcare setting