Cholinergic suppression: A postsynaptic mechanism of long-term associative learning

Food avoidance learning in the mollusc Pleurobranchaea entails reduction in the responsiveness of key brain interneurons in the feeding neural circuitry, the paracerebral feeding command interneurons (PCNs), to the neurotransmitter acetylcholine (AcCho). Food stimuli applied to the oral veil of an untrained animal depolarize the PCNs and induce the feeding motor program (FMP). Atropine (a muscarinic cholinergic antagonist) reversibly blocks the food-induced depolarization of the PCNs, implicating AcCho as the neurotransmitter mediating food detection. AcCho applied directly to PCN somata depolarizes them, indicating that the PCN soma membrane contains AcCho receptors and induces the FMP in the isolated central nervous system preparation. The AcCho response of the PCNs is mediated by muscariniclike receptors, since comparable depolarization is induced by muscarinic agonists (acetyl-ß -methylcholine, oxotremorine, pilocarpine), but not nicotine, and blocked by muscarinic antagonists (atropine, trifluoperazine). The nicotinic antagonist hexamethonium, however, blocked the AcCho response in four of six cases. When specimens are trained to suppress feeding behavior using a conventional food-avoidance learning paradigm (conditionally paired food and shock), AcCho applied to PCNs in the same concentration as in untrained animals causes little or no depolarization and does not initiate the FMP. Increasing the concentration of AcCho 10-100 times, however, induces weak PCN depolarization in trained specimens, indicating that learning diminishes but does not fully abolish AcCho responsiveness of the PCNs. This study proposes a cellular mechanism of long-term associative learning -- namely, postsynaptic modulation of neurotransmitter responsiveness in central neurons that could apply also to mammalian species

Geodynamic implications for zonal and meridional isotopic patterns across the northern Lau and North Fiji Basins

We present new Sr-Nd-Pb-Hf-He isotopic data for sixty-five volcanic samples from the northern Lau and North Fiji Basin. This includes forty-seven lavas obtained from forty dredge sites spanning an east-west transect across the Lau and North Fiji basins, ten ocean island basalt (OIB)-type lavas collected from seven Fijian islands, and eight OIB lavas sampled on Rotuma. For the first time we are able to map clear north-south and east-west geochemical gradients in 87Sr/86Sr across the northern Lau and North Fiji Basins: lavas with the most geochemically enriched radiogenic isotopic signatures are located in the northeast Lau Basin, while signatures of geochemical enrichment are diminished to the south and west away from the Samoan hotspot. Based on these geochemical patterns and plate reconstructions of the region, these observations are best explained by the addition of Samoa, Rurutu, and Rarotonga hotspot material over the past 4 Ma. We suggest that underplated Samoan material has been advected into the Lau Basin over the past ∼4 Ma. As the slab migrated west (and toward the Samoan plume) via rollback over time, younger and hotter (and therefore less viscous) underplated Samoan plume material was entrained. Thus, entrainment efficiency of underplated plume material was enhanced, and Samoan plume signatures in the Lau Basin became stronger as the trench approached the Samoan hotspot. The addition of subducted volcanoes to the Cook-Austral Volcanic Lineament material, first from the Rarotonga hotspot, then followed by the Rurutu hotspot, contributes to the extreme geochemical signatures observed in the northeast Lau Basin

Examining how the Dark Triad moderates the relationship between workplace victimization and workplace behavior

This study will examine the relationship between workplace victimization and workplace behavior. Furthermore, this study will examine how the Dark Triad of personality affects that relationship. The study will be conducted as a Masters’ Thesis at Middle Tennessee State University. We propose that the there is a positive relationship between workplace victimization and counterproductive work behaviors (CWB) and a negative relationship between workplace victimization and occupational citizenship behaviors (OCB). We also propose that the Dark Triad (narcissism, Machiavellianism, and psychopathy) each positively moderate the relationship between workplace victimization and CWB. Data on each of these constructs will be collected from participants through Amazon’s Mechanical Turk. This study is intended to help gain an understanding of the range of negative effects that workplace victimization can have on both victims and organizations at large. This study will allow researchers and practitioners alike to understand the negative consequences of workplace mistreatment; also, it may motivate organizations to establish policies to protect their employees from harm

Structural analysis of the carboxy terminal PH domain of pleckstrin bound to D-myo-inositol 1,2,3,5,6-pentakisphosphate

<p>Abstract</p> <p>Background</p> <p>Pleckstrin homology (PH) domains are one of the most prevalent domains in the human proteome and represent the major phosphoinositide-binding module. These domains are often found in signaling proteins and function predominately by targeting their host proteins to the cell membrane. Inositol phosphates, which are structurally similar to phosphoinositides, are not only known to play a role as signaling molecules but are also capable of being bound by PH domains.</p> <p>Results</p> <p>In the work presented here it is shown that the addition of commercial <it>myo</it>-inositol hexakisphosphate (IP₆) inhibited the binding of the carboxy terminal PH domain of pleckstrin (C-PH) to phosphatidylinositol 3,4-bisphosphate with an IC₅₀of 7.5 μM. In an attempt to characterize this binding structurally, C-PH was crystallized in the presence of IP₆and the structure was determined to 1.35 Å. Examination of the resulting electron density unexpectedly revealed the bound ligand to be D-<it>myo</it>-inositol 1,2,3,5,6-pentakisphosphate.</p> <p>Conclusion</p> <p>The discovery of D-<it>myo</it>-inositol 1,2,3,5,6-pentakisphosphate in the crystal structure suggests that the inhibitory effects observed in the binding studies may be due to this ligand rather than IP₆. Analysis of the protein-ligand interaction demonstrated that this <it>myo</it>-inositol pentakisphosphate isomer interacts specifically with protein residues known to be involved in phosphoinositide binding. In addition to this, a structural alignment of other PH domains bound to inositol phosphates containing either four or five phosphate groups revealed that the majority of phosphate groups occupy conserved locations in the binding pockets of PH domains. These findings, taken together with other recently reported studies suggest that <it>myo-</it>inositol pentakisphosphates could act to regulate PH domain-phosphoinositide interactions by directly competing for binding, thus playing an important role as signaling molecules.</p

Poverty Programs, Initiation Of Prenatal Care And The Rate Of Low Birthweight Births

This paper specifies and estimates an econometric model of low and very low birthweight rates for counties in the U.S. for the years 1975-1984. We focus on the impact of several specific public policy actions on use of prenatal care and the subsequent effect on birthweight outcomes. Our results point to strong racial differences in the impact of prenatal care on low birthweight rates. We also find that for the white population changes in income eligibility standards and expanded availability of publicly financed maternal and infant clinics have the strongest impacts on low birthweight rates.

DNAzyme-mediated recovery of small recombinant RNAs from a 5S rRNA-derived chimera expressed in Escherichia coli

Background: Manufacturing large quantities of recombinant RNAs by overexpression in a bacterial host is hampered by their instability in intracellular environment. To overcome this problem, an RNA of interest can be fused into a stable bacterial RNA for the resulting chimeric construct to accumulate in the cytoplasm to a sufficiently high level. Being supplemented with cost-effective procedures for isolation of the chimera from cells and recovery of the recombinant RNA from stabilizing scaffold, this strategy might become a viable alternative to the existing methods of chemical or enzymatic RNA synthesis. Results: Sequence encoding a 71-nucleotide recombinant RNA was inserted into a plasmid-borne deletion mutant of the Vibrio proteolyticus 5S rRNA gene in place of helix III - loop C segment of the original 5S rRNA. After transformation into Escherichia coli, the chimeric RNA (3譸en aRNA) was expressed constitutively from E. coli rrnB P1 and P2 promoters. The RNA chimera accumulated to levels that exceeded those of the host's 5S rRNA. A novel method relying on liquid solid partitioning of cellular constituents was developed for isolation of total RNA from bacterial cells. This protocol avoids toxic chemicals, and is therefore more suitable for large scale RNA purification than traditional methods. A pair of biotinylated 8-17 DNAzymes was used to bring about the quantitative excision of the 71-nt recombinant RNA from the chimera. The recombinant RNA was isolated by sequence-specific capture on beads with immobilized complementary deoxyoligonucleotide, while DNAzymes were recovered by biotin affinity chromatography for reuse. Conclusions:The feasibility of a fermentation-based approach for manufacturing large quantities of small RNAs in vivo using a "5S rRNA scaffold" strategy is demonstrated. The approach provides a route towards an economical method for the large-scale production of small RNAs including shRNAs, siRNAs and aptamers for use in clinical and biomedical research

DNAzyme-mediated recovery of small recombinant RNAs from a 5S rRNA-derived chimera expressed in Escherichia coli

<p>Abstract</p> <p>Background</p> <p>Manufacturing large quantities of recombinant RNAs by overexpression in a bacterial host is hampered by their instability in intracellular environment. To overcome this problem, an RNA of interest can be fused into a stable bacterial RNA for the resulting chimeric construct to accumulate in the cytoplasm to a sufficiently high level. Being supplemented with cost-effective procedures for isolation of the chimera from cells and recovery of the recombinant RNA from stabilizing scaffold, this strategy might become a viable alternative to the existing methods of chemical or enzymatic RNA synthesis.</p> <p>Results</p> <p>Sequence encoding a 71-nucleotide recombinant RNA was inserted into a plasmid-borne deletion mutant of the <it>Vibrio proteolyticus </it>5S rRNA gene in place of helix III - loop C segment of the original 5S rRNA. After transformation into <it>Escherichia coli</it>, the chimeric RNA (3×<it>pen </it>aRNA) was expressed constitutively from <it>E. coli rrnB </it>P1 and P2 promoters. The RNA chimera accumulated to levels that exceeded those of the host's 5S rRNA. A novel method relying on liquid-solid partitioning of cellular constituents was developed for isolation of total RNA from bacterial cells. This protocol avoids toxic chemicals, and is therefore more suitable for large scale RNA purification than traditional methods. A pair of biotinylated 8-17 DNAzymes was used to bring about the quantitative excision of the 71-nt recombinant RNA from the chimera. The recombinant RNA was isolated by sequence-specific capture on beads with immobilized complementary deoxyoligonucleotide, while DNAzymes were recovered by biotin affinity chromatography for reuse.</p> <p>Conclusions</p> <p>The feasibility of a fermentation-based approach for manufacturing large quantities of small RNAs <it>in vivo </it>using a "5S rRNA scaffold" strategy is demonstrated. The approach provides a route towards an economical method for the large-scale production of small RNAs including shRNAs, siRNAs and aptamers for use in clinical and biomedical research.</p

U.S. State‐Supported Dental Schools: Financial Projections and Implications

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153620/1/jddj002203372006703tb04080x.pd

U.S. State‐Supported Dental Schools: Financial Projections and Implications

This article examines the impact of financial trends in state‐supported dental schools on full‐time clinical faculty; the diversity of dental students and their career choices; investments in physical facilities; and the place of dentistry in research universities. The findings of our study are the following: the number of students per full‐time clinical faculty member increased; the three schools with the lowest revenue increases lost a third of their full‐time clinical faculty; more students are from wealthier families; most schools are not able to adequately invest in their physical plant; and more than half of schools have substantial NIH‐funded research programs. If current trends continue, the term “crisis” will describe the situation faced by most dental schools. Now is the time to build the political consensus needed to develop new and more effective strategies to educate the next generation of American dentists and to keep dental education primarily based in research universities. The future of the dental profession and the oral health of the American people depend on it.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153587/1/jddj002203372008722suppltb04487x.pd

String windings in the early universe

We study string dynamics in the early universe. Our motivation is the proposal of Brandenberger and Vafa, that string winding modes may play a key role in decompactifying three spatial dimensions. We model the universe as a homogeneous but anisotropic 9-torus filled with a gas of excited strings. We adopt initial conditions which fix the dilaton and the volume of the torus, but otherwise assume all states are equally likely. We study the evolution of the system both analytically and numerically to determine the late-time behavior. We find that, although dynamical evolution can indeed lead to three large spatial dimensions, such an outcome is not statistically favored.Comment: 26 pages, LaTeX, 4 eps figure