Left−Right Asymmetry Defect in the Hippocampal Circuitry Impairs Spatial Learning and Working Memory in iv Mice

Although left-right (L−R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv) mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness) in the synaptic distribution of theε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L−R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory

Surviving pediatric intensive care: physical outcome after 3 months

Objective: This study investigated the prevalence and nature of physical and neurocognitive sequelae in pediatric intensive care unit ( PICU) survivors. Design and setting: Prospective follow-up study 3 months after discharge from a 14-bed tertiary PICU in The Netherlands. Patients and participants: The families of 250 previously healthy children unexpectedly admitted to the PICU were invited to visit the outpatient follow-up clinic for structured medical examination of the child 3 months after discharge; 186 patients were evaluated. Measurements and results: Pediatric Cerebral Performance Category ( PCPC) and Pediatric Overall Performance Category ( POPC) values were determined at PICU discharge, at the outpatient follow-up clinic, and retrospectively before admission to the PICU. We found that 69% of children had physical sequelae. In 30% of cases these were caused by a previously unknown illness and in 39% by acquired morbidity. In 8% of the children the acquired morbidity was related to complications from PICU procedures. Three months after discharge 77% of the children had normal PCPC scores and 31% had normal POPC scores. Conclusions: Our results indicate that PICU survival may be associated with substantial physical sequelae. Structured follow-up research, preferably by multicenter studies, is warranted in PICU survivor

Enhanced genetic maps from family-based disease studies: population-specific comparisons

Abstract Background Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps. Results We collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent), Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths. Conclusions Our new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI) for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.http://deepblue.lib.umich.edu/bitstream/2027.42/112826/1/12881_2010_Article_748.pd

Improved Outcome Prediction Using CT Angiography in Addition to Standard Ischemic Stroke Assessment: Results from the STOPStroke Study

Purpose: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS.2. Strokes were classified as ‘‘major’ ’ by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was#7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores.10. Results: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p,0.0001). Combining NIHSS with BASIS was highly predictive: 77.6 % (114/147) classified as NIHSS.10/BASIS+ had poor outcomes, versus 21.5 % (77/358) with NIHSS#10/BASIS2 (p,0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95 % CI: 7.9 to 20.0

Genetic Evidence Highlights Potential Impacts of By-Catch to Cetaceans

Incidental entanglement in fishing gear is arguably the most serious threat to many populations of small cetaceans, judging by the alarming number of captured animals. However, other aspects of this threat, such as the potential capture of mother-offspring pairs or reproductive pairs, could be equally or even more significant but have rarely been evaluated. Using a combination of demographic and genetic data we provide evidence that i) Franciscana dolphin pairs that are potentially reproductive and mother-offspring pairs form temporal bonds, and ii) are entangled simultaneously. Our results highlight potential demographic and genetic impacts of by-catch to cetacean populations: the joint entanglement of mother-offspring or reproductive pairs, compared to random individuals, might exacerbate the demographic consequences of by-catch, and the loss of groups of relatives means that significant components of genetic diversity could be lost together. Given the social nature of many odontocetes (toothed cetaceans), we suggest that these potential impacts could be rather general to the group and therefore by-catch could be more detrimental than previously considered

Finding regulatory elements and regulatory motifs: a general probabilistic framework

Over the last two decades a large number of algorithms has been developed for regulatory motif finding. Here we show how many of these algorithms, especially those that model binding specificities of regulatory factors with position specific weight matrices (WMs), naturally arise within a general Bayesian probabilistic framework. We discuss how WMs are constructed from sets of regulatory sites, how sites for a given WM can be discovered by scanning of large sequences, how to cluster WMs, and more generally how to cluster large sets of sites from different WMs into clusters. We discuss how 'regulatory modules', clusters of sites for subsets of WMs, can be found in large intergenic sequences, and we discuss different methods for ab initio motif finding, including expectation maximization (EM) algorithms, and motif sampling algorithms. Finally, we extensively discuss how module finding methods and ab initio motif finding methods can be extended to take phylogenetic relations between the input sequences into account, i.e. we show how motif finding and phylogenetic footprinting can be integrated in a rigorous probabilistic framework. The article is intended for readers with a solid background in applied mathematics, and preferably with some knowledge of general Bayesian probabilistic methods. The main purpose of the article is to elucidate that all these methods are not a disconnected set of individual algorithmic recipes, but that they are just different facets of a single integrated probabilistic theory

Krill Excretion Boosts Microbial Activity in the Southern Ocean

Antarctic krill are known to release large amounts of inorganic and organic nutrients to the water column. Here we test the role of krill excretion of dissolved products in stimulating heterotrophic bacteria on the basis of three experiments where ammonium and organic excretory products released by krill were added to bacterial assemblages, free of grazers. Our results demonstrate that the addition of krill excretion products (but not of ammonium alone), at levels expected in krill swarms, greatly stimulates bacteria resulting in an order-of-magnitude increase in growth and production. Furthermore, they suggest that bacterial growth rate in the Southern Ocean is suppressed well below their potential by resource limitation. Enhanced bacterial activity in the presence of krill, which are major sources of DOC in the Southern Ocean, would further increase recycling processes associated with krill activity, resulting in highly efficient krill-bacterial recycling that should be conducive to stimulating periods of high primary productivity in the Southern Ocean.This research is a contribution to projects ICEPOS (REN2002-04165-CO3-O2) and ATOS (POL2006-00550/CTM), funded by the Spanish Ministry of Science and Innovation

Maternal Behavior is Impaired in Female Mice Lacking Type 3 Adenylyl Cyclase

Although chemosensory signals generated by mouse pups may trigger maternal behavior of females, the mechanism for detection of these signals has not been fully defined. As some odorant receptors are coupled to the type 3 adenylyl cyclase (AC3), we evaluated the role of AC3 for maternal behavior using AC3−/− female mice. Here, we report that maternal behavior is impaired in virgin and postpartum AC3−/− mice. Female AC3−/− mice failed the pup retrieval assay, did not construct well-defined nests, and did not exhibit maternal aggression. Furthermore, AC3−/− females could not detect odorants or pup urine in the odorant habituation test and were unable to detect pups by chemoreception. In contrast to wild-type mice, AC activity in main olfactory epithelium (MOE) preparations from AC3−/− female mice was not stimulated by odorants or pheromones. Moreover, odorants and pheromones did not evoke electro-olfactogram (EOG) responses in the MOE of AC3−/− female mice. We hypothesize that the detection of chemical signals that trigger maternal behavior in female mice depends upon AC3 in the MOE

Benthic pH gradients across a range of shelf sea sediment types linked to sediment characteristics and seasonal variability

This study used microelectrodes to record pH profiles in fresh shelf sea sediment cores collected across a range of different sediment types within the Celtic Sea. Spatial and temporal variability was captured during repeated measurements in 2014 and 2015. Concurrently recorded oxygen microelectrode profiles and other sedimentary parameters provide a detailed context for interpretation of the pH data. Clear differences in profiles were observed between sediment type, location and season. Notably, very steep pH gradients exist within the surface sediments (10–20 mm), where decreases greater than 0.5 pH units were observed. Steep gradients were particularly apparent in fine cohesive sediments, less so in permeable sandier matrices. We hypothesise that the gradients are likely caused by aerobic organic matter respiration close to the sediment–water interface or oxidation of reduced species at the base of the oxic zone (NH4+, Mn2+, Fe2+, S−). Statistical analysis suggests the variability in the depth of the pH minima is controlled spatially by the oxygen penetration depth, and seasonally by the input and remineralisation of deposited organic phytodetritus. Below the pH minima the observed pH remained consistently low to maximum electrode penetration (ca. 60 mm), indicating an absence of sub-oxic processes generating H+ or balanced removal processes within this layer. Thus, a climatology of sediment surface porewater pH is provided against which to examine biogeochemical processes. This enhances our understanding of benthic pH processes, particularly in the context of human impacts, seabed integrity, and future climate changes, providing vital information for modelling benthic response under future climate scenarios