An oscillatory interference model of grid cell firing

We expand upon our proposal that the oscillatory interference mechanism proposed for the phase precession effect in place cells underlies the grid-like firing pattern of dorsomedial entorhinal grid cells (O'Keefe and Burgess (2005) Hippocampus 15:853-866). The original one-dimensional interference model is generalized to an appropriate two-dimensional mechanism. Specifically, dendritic subunits of layer 11 medial entorhinal stellate cells provide multiple linear interference patterns along different directions, with their product determining the firing of the cell. Connection of appropriate speed- and direction- dependent inputs onto dendritic subunits could result from an unsupervised learning rule which maximizes postsynaptic firing (e.g. competitive learning). These inputs cause the intrinsic oscillation of subunit membrane potential to. increase above theta frequency by an amount proportional to the animal's speed of running in the "preferred" direction. The phase difference between this oscillation and a somatic input at theta-frequency essentially integrates velocity so that the interference of the two oscillations reflects distance traveled in the preferred direction. The overall grid pattern is maintained in environmental location by phase reset of the grid cell by place cells receiving sensory input from the environment, and environmental boundaries in particular. We also outline possible variations on the basic model, including the generation of grid-like firing via the interaction of multiple cells rather than via multiple dendritic subunits. Predictions of the interference model are given for the frequency composition of EEG power spectra and temporal autocorrelograms of grid cell firing as functions of the speed and direction of running and the novelty of the environment. (C) 2007 Wiley-Liss, Inc

Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences

Five distinct patterns of DNA replication have been identified during S-phase in asynchronous and synchronous cultures of mammalian cells by conventional fluorescence microscopy, confocal laser scanning microscopy, and immunoelectron microscopy. During early S-phase, replicating DNA (as identified by 5-bromodeoxyuridine incorporation) appears to be distributed at sites throughout the nucleoplasm, excluding the nucleolus. In CHO cells, this pattern of replication peaks at 30 min into S-phase and is consistent with the localization of euchromatin. As S-phase continues, replication of euchromatin decreases and the peripheral regions of heterochromatin begin to replicate. This pattern of replication peaks at 2 h into S-phase. At 5 h, perinucleolar chromatin as well as peripheral areas of heterochromatin peak in replication. 7 h into S-phase interconnecting patches of electron-dense chromatin replicate. At the end of S-phase (9 h), replication occurs at a few large regions of electron-dense chromatin. Similar or identical patterns have been identified in a variety of mammalian cell types. The replication of specific chromosomal regions within the context of the BrdU-labeling patterns has been examined on an hourly basis in synchronized HeLa cells. Double labeling of DNA replication sites and chromosome-specific alpha-satellite DNA sequences indicates that the alpha-satellite DNA replicates during mid S-phase (characterized by the third pattern of replication) in a variety of human cell types. Our data demonstrates that specific DNA sequences replicate at spatially and temporally defined points during the cell cycle and supports a spatially dynamic model of DNA replication

Can antlions discriminate?: testing the limits of associative learning in antlion Myrmeleon immaculatus.

Behavioral EcologyDespite the abundance of literature on associative learning in insects, the ability of insects to learn to discriminate between different stimuli through associative learning remains largely unstudied. Antlion Myrmeleon immaculatus larvae construct steep conical pitfall traps in the sand that they use to capture prey. Previous studies have show that M. immaculatus larvae can learn to associate vibrational stimuli with food through conditioning. In this study, we attempt to replicate these results and determine whether M. immaculatus larvae can learn to discriminate between different vibrational stimuli. We failed to demonstrate any associative learning capacity in our larvae, hypothesizing that this failure is due to our experimental design. I discuss recommendations for future studies on discriminatory learning in antlions.http://deepblue.lib.umich.edu/bitstream/2027.42/101743/1/O'Keefe_Cullen_2013.pd

Consumer responses to a future UK food system

Purpose– The purpose of this paper is to describe research exploring consumer responses to potential changes in food-related practices to mitigate and adapt to climate change.Design/methodology/approach– Six focus groups explored consumer responses to measures to intended to mitigate the emissions from, and adapt to the impacts of climate change. These included: meat reduction, greater reliance on seasonal British food, meal replacement tablets, laboratory grown meat, communal eating houses, genetically modified food and food waste. Practice theory provided the lens to interpret the changes to meanings, competences and materials associated with food consumption.Findings– Changes that could be assimilated within existing competencies were viewed more positively, with lack of competence a key barrier to accommodating change. At present, climate change and sustainability do not influence purchasing decisions. Policy measures delivering multiple benefits (“win-wins”), of which environmental performance may be one, stand an improved chance of establishing more sustainable practices than those focusing exclusively on environmental drivers.Originality/value– Awareness of the role of sustainable food systems in the context of anthropogenic climate change is growing. Whilst scientific and technological research explores methods for reducing emissions and building resilience in food supply chains to changes in climate, there is comparatively little study of how consumers perceive these proposed “solutions”. This research provides a comprehensive overview of consumer responses to potential changes in eating practices related to climate change mitigation and adaptation and is of value to policy makers, academics and practitioners across the food supply chain.</jats:sec

A plesiosaur containing an ichthyosaur embryo as stomach contents from the Sundance Formation of the Bighorn Basin, Wyoming

Herein we report the discovery of an ichthyosaur embryo from the Upper Member of the Sundance Formation (Oxfordian) of the Bighorn Basin, Wyoming. The specimen is the first known ichthyosaur embryo from the Upper Jurassic, and is the first Jurassic ichthyosaur embryo from North America. The embryo was discovered in close association with the abdomen of an articulated partial plesiosaur skeleton, and several lines of evidence support the interpretation of the embryo as plesiosaur stomach contents. The small size and extremely poor ossification of the embryo indicate that the animal was probably not a neonate. Although the taxonomic affinities of the fossil are unknown, the large ichthyosaurian (sensu stricto) Opthalmosaurus natans is the only known ichthyosaur from the Sundance Formation, and the embryo may belong to that taxon

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Cerebral blood flow and Aβ-amyloid estimates by WARM analysis of [¹¹C]PiB uptake distinguish among and between neurodegenerative disorders and aging

Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [C]Pittsburgh Compound B ([C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer's disease, and healthy volunteers. The method introduces two approaches to the identification of brain pathology related to amyloid accumulation, (1) a novel analysis of amyloid binding based on the late washout of the tracer from brain tissue, and (2) the simultaneous estimation of absolute cerebral blood flow indices (sCBF) from the early accumulation of the tracer in brain tissue. Objective: We tested the hypothesis that a change of cerebral blood flow is correlated with the degree of tracer [C]PiB retention, reflecting dendritic spine pathology and consequent inhibition of brain energy metabolism and reduction of blood flow by neurovascular coupling in neurodegenerative disorders, including Alzheimer's disease. Methods: Previously reported images of [C]PiB retention in brain of 29 subjects with cognitive impairment or dementia [16 Alzheimer's Disease (AD), eight subjects with dementia with Lewy bodies (DLB), five patients with frontotemporal lobar degeneration (FTLD), five patients with mild cognitive impairment, and 29 age-matched healthy control subjects (HC)], underwent analysis of PiB delivery and retention by means of WARM for quantitation of [C]PiB's binding potentials (BP) and correlated surrogate cerebral blood flow (sCBF) estimates, based on the [C]PiB images, compared to estimates by conventional Standard Uptake Value Ratio (SUVR) of [C]PiB retention with cerebellum gray matter as reference. Receiver Operating Characteristics (ROC) revealed the power of discrimination among estimates. Results: For AD, the discriminatory power of [C]PiB binding potential (BP) by WARM exceeded the power of SUVR that in turn exceeded the power of sCBF estimates. Differences of [C]PiB binding and sCBF measures between AD and HC both were highly significant (p < 0.001). For all the dementia groups as a whole, sCBF estimates revealed the greatest discrimination between the patient and HC groups. WARM resolves a major issue of amyloid load quantification with [C]PiB in human brain by determining absolute sCBF and amyloid load measures from the same images. The two parameter approach provides key discriminary information in AD for which [C]PiB traditionally is used, as well as for the distinct flow deficits in FTLD, and the marked parietal and occipital lobe flow deficits in DLB. Conclusion: We conclude that WARM yields estimates of two important variables that together discriminate among patients with dementia, including AD, and healthy volunteers, with ROC that are superior to conventional methods of analysis. The distinction between estimates of flow and amyloid load from the same dynamic emission tomograms provides valuable pathogenetic information

Disruption of pre-mRNA splicing in vivo results in reorganization of splicing factors

We have examined the functional significance of the organization of pre-mRNA splicing factors in a speckled distribution in the mammalian cell nucleus. Upon microinjection into living cells of oligonucleotides or antibodies that inhibit pre-mRNA splicing in vitro, we observed major changes in the organization of splicing factors in vivo. Interchromatin granule clusters became uniform in shape, decreased in number, and increased in both size and content of splicing factors, as measured by immunofluorescence. These changes were transient and the organization of splicing factors returned to their normal distribution by 24 h following microinjection. Microinjection of these oligonucleotides or antibodies also resulted in a reduction of transcription in vivo, but the oligonucleotides did not inhibit transcription in vitro. Control oligonucleotides did not disrupt splicing or transcription in vivo. We propose that the reorganization of splicing factors we observed is the result of the inhibition of splicing in vivo

Testing the performance of the ENRICHD Social Support Instrument in cardiac patients

BACKGROUND: Previous investigations suggest an important role of social support in the outcomes of patients treated for ischemic heart disease. The ENRICHD Social Support Instrument (ESSI) is a 7-item self-report survey that assesses social support. Validity and reliability of the ESSI, however, has not been formally tested in patients undergoing percutaneous coronary intervention (PCI). METHODS: The ESSI, along with the Short Form-36 (SF-36), was sequentially administered to a cohort of 271 patients undergoing PCI. The test-retest reliability was examined with an intra-class correlation coefficient by comparing scores among 174 patients who completed both instruments 5 and 6 months after their procedure. Internal reliability was assessed using Cronbach's alpha at the time of patients' baseline procedure. The concurrent validity of the ESSI was assessed by comparing scores between depressed (MHI-5 score < 44) vs. non-depressed patients. The correlation between the ESSI and the SF-36 Social Functioning sub-scale, an accepted measure of social functioning, was also examined. RESULTS: Test-retest reliability showed no significant differences in mean scores among ESSI questionnaires administered 1 month apart (27.8+/-1.4 vs 27.8+/-1.5, p = 0.98). The intra-class correlation coefficient was 0.94 and Cronbach's alpha was 0.88. Mean ESSI scores were significantly lower among depressed vs. non-depressed patients (24.6+/-1.7 vs 27+/-1.4, p < 0.018) and a positive albeit modest correlation with social functioning was seen (r = 0.19, p = 0.002). CONCLUSION: The ESSI appears to be a valid and reliable measure of social support in patients undergoing treatment for coronary artery disease. It may prove to be a valuable method of controlling for patient variability in outcomes studies where the outcomes are related to patients' social support