Hyperglycemia alters enzyme activity and cell number in spinal sensory ganglia

Peripheral sensory diabetic neuropathy is characterized by morphological, electrophysiological and neurochemical changes to a subpopulation of primary afferent neurons. Here, we utilized a transgenic mouse model of diabetes (OVE26) and age-matched controls to histologically examine the effect of chronic hyperglycemia on the activity or abundance of the enzymes acid phosphatase, cytochrome oxidase and NADPH-diaphorase in primary sensory neuron perikarya and the dorsal horn of the spinal cord. Quantitative densitometric characterization of enzyme reaction product revealed significant differences between diabetic, compared to control, animals for all three enzymes. Levels of acid phosphatase reaction product were found to be significantly reduced in both small diameter primary sensory somata and the dorsal horn. Cytochrome oxidase activity was found to be significantly lower in small primary sensory somata while NADPH-diaphorase labeling was found to be significantly higher in small primary sensory somata and significantly lower in the dorsal horn. In addition to these observed biochemical changes, ratiometric analysis of the number of small versus large diameter primary sensory perikarya in diabetic and control animals demonstrated a quantifiable decrease in the number of small diameter cells in the spinal ganglia of diabetic mice. These results suggest that the OVE26 model of diabetes mellitus produces an identifiable disturbance in specific metabolic pathways of select cells in the sensory nervous system and that this dysfunction may reflect the progression of a demonstrated cell loss

Localization of SSeCKS in unmyelinated primary sensory neurons

<p>Abstract</p> <p>Background</p> <p>SSeCKS (<it>S</it>rc <it>S</it>uppr<it>E</it>ssed <it>C K</it>inase <it>S</it>ubstrate) is a proposed protein kinase C substrate/A kinase anchoring protein (AKAP) that has recently been characterized in the rat peripheral nervous system. It has been shown that approximately 40% of small primary sensory neurons contain SSeCKS-immunoreactivity in a population largely separate from substance P (95.2%), calcitonin gene related peptide (95.3%), or fluoride resistant acid phosphatase (55.0%) labeled cells. In the spinal cord, it was found that SSeCKS-immunoreactive axon collaterals terminate in the dorsal third of lamina II outer in a region similar to that of unmyelinated C-, or small diameter myelinated Aδ-, fibers. However, the precise characterization of the anatomical profile of the primary sensory neurons containing SSeCKS remains to be determined. Here, immunohistochemical labeling at the light and ultrastructural level is used to clarify the myelination status of SSeCKS-containing sensory neuron axons and to further clarify the morphometric, and provide insight into the functional, classification of SSeCKS-IR sensory neurons.</p> <p>Methods</p> <p>Colocalization studies of SSeCKS with myelination markers, ultrastructural localization of SSeCKS labeling and ablation of largely unmyelinated sensory fibers by neonatal capsaicin administration were all used to establish whether SSeCKS containing sensory neurons represent a subpopulation of unmyelinated primary sensory C-fibers.</p> <p>Results</p> <p>Double labeling studies of SSeCKS with CNPase in the dorsal horn and Pzero in the periphery showed that SSeCKS immunoreactivity was observed predominantly in association with unmyelinated primary sensory fibers. At the ultrastructural level, SSeCKS immunoreactivity was most commonly associated with axonal membrane margins of unmyelinated fibers. In capsaicin treated rats, SSeCKS immunoreactivity was essentially obliterated in the dorsal horn while in dorsal root ganglia quantitative analysis revealed a 43% reduction in the number of SSeCKS-labeled cells. This attenuation is concomitant with a decrease in fluoride-resistant acid phosphatase labeled fibers in the spinal cord dorsal horn and small neuronal somata in sensory ganglia.</p> <p>Conclusion</p> <p>These results demonstrate that SSeCKS is primarily localized within a distinct subpopulation of small diameter, largely unmyelinated C-fiber primary sensory neurons putatively involved in nociception.</p

Assessment of crystallographic orientation effects on secondary ion mass spectrometry (SIMS) analysis of cassiterite

Crystallographic orientation effects on ion microprobe analyses for U-Pb and O-isotopes have been reported for a number of oxide minerals, including rutile (TiO₂) and baddeleyite (ZrO₂). Here we evaluate the effects of crystal orientation on U-Pb and O-isotopic data measured by ion microprobe on cassiterite (SnO₂), which is isostructural with rutile. The crystallographic orientations of mounted and polished grains of cassiterite were determined by electron backscatter diffraction (EBSD). Those grains were then analysed for U-Th-Pb isotopes and ¹⁸O/¹⁶O compositions using the SHRIMP RG and SHRIMP SI ion microprobes, respectively. Based on these data, cassiterite appears to show no dependence of key measurement parameters such as UO₂/UO, Pb/UO, or ¹⁸O/¹⁶O ratios at the achieved precision with crystallographic orientation. The contrasting behaviour of isostructural cassiterite and rutile provides new insights into the mechanisms leading to crystallographic orientation effects during ion microprobe analyses with electronic structure proposed as being a significant factor

The Oregon Guide to Private Fund Raising for Local Governments

24 pagesNonprofit organizations thrive on the altruism of citizens, and actively court donors for major gifts. Yet individual gifts to government agencies are often unexpected, sporadic, and initiated by the donor. This article introduces the phenomenon of private giving to local governments and tests hypotheses regarding the expected forms of giving to public agencies. Results indicate that philanthropy is and will likely remain a minor and highly variable source of revenue, making it an ill‐suited replacement for broad‐based tax revenue. However, deliberate government efforts to provide a suitable environment for private donations appear to succeed in attracting more gifts per capita.We thank the Oregon League of Cities for providing resources necessary for the statewide internet survey of municipal managers referenced in this guide, and for distributing this guide to the Oregon League of Cities membership

Neoliberal and Neoconservative Immiseration Capitalism in England: Policies and Impacts on Society and on Education

In this article we firstly set out the facts about the current stage of capitalism, the Immiseration stage of neoliberal capitalism in England. We note its relationship with conservatism and neo-conservatism. We identify increased societal inequalities, the assault by the capitalist state on its opponents, and proceed to describe and analyse what neoliberalism and neo-conservatism have done and are doing to education in England- in the schools, further education, and university sectors. We present two testimonies about the impacts of neoliberalism/ neo-conservatism, one from the school sector, one from the further / vocational education sector, as a means of describing, analysing, and then theorising the parameters of the neoliberal/ neoconservative restructuring education and its impacts. We conclude by further theorising this. With the election of a Conservative majority in the 7 May 2015 general election in the UK, the policies and processes of neoliberalisation and neoconservatisation are being intensified

Identification of non-dot/icm suppressors of the Legionella pneumophila △dotL lethality phenotype

Legionella pneumophila, a causative agent of bacterial pneumonia, survives inside phagocytic cells by avoiding rapid targeting to the lysosome. This bacterium utilizes a type IVB secretion system, encoded by the dot/icm genes, to replicate inside host cells. DotL, a critical component of the Dot/Icm secretion apparatus, functions as the type IV coupling protein. In contrast to most dot/icm genes, which are dispensable for growth on bacteriological media, dotL is required for the viability of wild-type L. pneumophila. Previously we reported that ΔdotL lethality could be suppressed by inactivation of the Dot/Icm complex via mutations in other dot/icm genes. Here we report the isolation of non-dot/icm suppressors of this phenotype. These ΔdotL suppressors include insertions that disrupt the function of the L. pneumophila homologs of cpxR, djlA, lysS, and two novel open reading frames, lpg0742 and lpg1594, that we have named ldsA and ldsB for lethality of ΔdotL suppressor. In addition to suppressing ΔdotL lethality, inactivation of these genes in a wild-type strain background causes a range of defects in L. pneumophila virulence traits, including intracellular growth, implicating these factors in the proper function of the Dot/Icm complex. Consistent with previous data showing a role for the cpx system in regulating expression of several dot/icm genes, the cpxR insertion mutant produced decreased levels of three Dot/Icm proteins, DotA, IcmV, and IcmW. The remaining four suppressors did not affect the steady-state levels of any Dot/Icm protein and are likely to represent the first identified factors necessary for assembly and/or activation of the Dot/Icm secretion complex

Validity and Reliability of Scores Obtained on Multiple-Choice Questions: Why Functioning Distractors Matter

Purpose Plausible distractors are important for accurate measurement of knowledge via multiple-choice questions (MCQs). This study demonstrates the impact of higher distractor functioning on validity and reliability of scores obtained on MCQs. Methods Free-response (FR) and MCQ versions of a neurohistology practice exam were given to four cohorts of Year 1 medical students. Consistently non-functioning multiple-choice distractors (<5% selection frequency) were replaced with those developed from incorrect responses on FR version of the items, followed by administration of the revised MCQ version to subsequent two cohorts. Validity was assessed by comparing an index of expected MCQ difficulty with an index of observed MCQ difficulty, while reliability was assessed via Cronbach’s alpha coefficient before and after replacement of consistently non-functioning distractors. Result Pre-intervention, effect size (Cohen’s d) of the difference between mean expected and observed MCQ difficulty indices was noted to be 0.4 – 0.59. Post-intervention, this difference reduced to 0.15 along with an increase in Cronbach’s alpha coefficient of scores obtained on MCQ version of the exam. Conclusion Multiple-choice distractors developed from incorrect responses on free-response version of the items enhance the validity and reliability of scores obtained on MCQs

The Otterbein Miscellany - December 1980

https://digitalcommons.otterbein.edu/miscellany/1014/thumbnail.jp

Baryogenesis from Primordial Blackholes after Electroweak Phase Transition

Incorporating a realistic model for accretion of ultra-relativistic particles by primordial blackholes (PBHs), we study the evolution of an Einstein-de Sitter universe consisting of PBHs embedded in a thermal bath from the epoch $\sim 10^{-33}$ sec to $\sim 5\times 10^{-9}$ sec. In this paper we use Barrow et al's ansatz to model blackhole evaporation in which the modified Hawking temperature goes to zero in the limit of the blackhole attaining a relic state with mass $\sim m_{pl}$. Both single mass PBH case as well as the case in which blackhole masses are distributed in the range $8\times 10^2 - 3\times 10^5$ gm have been considered in our analysis. Blackholes with mass larger than $\sim 10^5$ gm appear to survive beyond the electroweak phase transition and, therefore, successfully manage to create baryon excess via $X-\bar X$ emissions, averting the baryon number wash-out due to sphalerons. In this scenario, we find that the contribution to the baryon-to-entropy ratio by PBHs of initial mass $m$ is given by $\sim \epsilon \zeta (m/1 {gm})^{-1}$, where $\epsilon$ and $\zeta$ are the CP-violating parameter and the initial mass fraction of the PBHs, respectively. For $\epsilon$ larger than $\sim 10^{-4}$, the observed matter-antimatter asymmetry in the universe can be attributed to the evaporation of PBHs.Comment: Latex2e file with seven figures included as postscript file

High-Redshift Quasars Found in Sloan Digital Sky Survey Commissioning Data II: The Spring Equatorial Stripe

This is the second paper in a series aimed at finding high-redshift quasars from five-color (u'g'r'i'z') imaging data taken along the Celestial Equator by the Sloan Digital Sky Survey (SDSS) during its commissioning phase. In this paper, we present 22 high-redshift quasars (z>3.6) discovered from ~250 deg^2 of data in the spring Equatorial Stripe, plus photometry for two previously known high-redshift quasars in the same region of sky. Our success rate of identifying high-redshift quasars is 68%. Five of the newly discovered quasars have redshifts higher than 4.6 (z=4.62, 4.69, 4.70, 4.92 and 5.03). All the quasars have i* < 20.2 with absolute magnitude -28.8 < M_B < -26.1 (h=0.5, q_0=0.5). Several of the quasars show unusual emission and absorption features in their spectra, including an object at z=4.62 without detectable emission lines, and a Broad Absorption Line (BAL) quasar at z=4.92.Comment: 28 pages, AJ in press (Jan 2000), final version with minor changes; high resolution finding charts available at http://www.astro.princeton.edu/~fan/paper/qso2.htm