Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor in vivo Using Fluorinated Bisquinolines

Antimalarials can interact with heme covalently, by - interactions or hydrogen bonding. Consequently, the prototropy of 4-aminoquinolines and quinoline methanols was investigated using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen due to electronic rather than steric factors. In gas phase calculations, 7-substituted mono- and bis-4-aminoquinolines were preferentially protonated at the endocyclic quinoline nitrogen. By contrast, compounds with a trifluoromethyl substituent on both the 2- and 8-positions, reversed the order of protonation which now favored the exocyclic secondary amine nitrogen at the 4-position. Loss of antimalarial efficacy by CF3 groups simultaneously occupying the 2- and 8-positions was recovered if the CF3 group occupied the 7-position. Hence, trifluromethyl groups buttressing quinolinyl nitrogen shifted binding of antimalarials to hematin, enabling switching from endocyclic to the exocyclic N. Both theoretical calculations (DFT calculations: B3LYP/6- 31+G*) and crystal structure of (±)-trans-N1,N2-bis-(2,8-ditrifluoromethylquinolin-4- yl)cyclohexane-1,2-diamine were used to reveal preferred mode(s) of interaction with hematin. The order of antimalarial activity in vivo followed the capacity for a redox change of the iron(III)state which has important implications for the future rational design of 4- aminoquinoline antimalarials

Expression of therapeutic misconception amongst Egyptians: a qualitative pilot study

<p>Abstract</p> <p>Background</p> <p>Studies have shown that research participants fail to appreciate the difference between research and medical care, labeling such phenomenon as a "therapeutic misconception" (TM). Since research activity involving human participants is increasing in the Middle East, qualitative research investigating aspects of TM is warranted. Our objective was to assess for the existence of therapeutic misconception amongst Egyptians.</p> <p>Methods</p> <p><it>Study Tool: </it>We developed a semi-structured interview guide to elicit the knowledge, attitudes, and perspectives of Egyptians regarding medical research.</p> <p><it>Setting: </it>We recruited individuals from the outpatient settings (public and private) at Ain Shams University in Cairo, Egypt.</p> <p><it>Analysis: </it>Interviews were taped, transcribed, and translated. We analyzed the content of the transcribed text to identify the presence of a TM, defined in one of two ways: TM₁= inaccurate beliefs about how individualized care can be compromised by the procedures in the research and TM₂= inaccurate appraisal of benefit obtained from the research study.</p> <p>Results</p> <p>Our findings showed that a majority of participants (11/15) expressed inaccurate beliefs regarding the degree with which individualized care will be maintained in the research setting (TM₁) and a smaller number of participants (5/15) manifested an unreasonable belief in the likelihood of benefits to be obtained from a research study (TM₂). A total of 12 of the 15 participants were judged to have expressed a TM on either one of these bases.</p> <p>Conclusion</p> <p>The presence of TM is not uncommon amongst Egyptian individuals. We recommend further qualitative studies investigating aspects of TM involving a larger sample size distinguished by different types of illnesses and socio-economic variables, as well as those who have and have not participated in clinical research.</p

Simple mindreading abilities predict complex theory of mind: developmental delay in autism spectrum disorders

Theory of Mind (ToM) is impaired in individuals with Autism Spectrum Disorders (ASD). The aims of this study were to: i) examine the developmental trajectories of ToM abilities in two different mentalizing tasks in children with ASD compared to TD children; and ii) to assess if a ToM simple test known as Eyes-test could predict performance on the more advanced ToM task, i.e. Comic Strip test. Based on a sample of 37 children with ASD and 55 TD children, our results revealed slower development at varying rates in all ToM measures in children with ASD, with delayed onset compared to TD children. These results could stimulate new treatments for social abilities, which would lessen the social deficit in ASD

The Class of All Natural Implicative Expansions of Kleene’s Strong Logic Functionally Equivalent to Łukasiewicz’s 3-Valued Logic Ł3

25 p.We consider the logics determined by the set of all natural implicative expansions of Kleene’s strong 3-valued matrix (with both only one and two designated values) and select the class of all logics functionally equivalent to Łukasiewicz’s 3-valued logic Ł3. The concept of a “natural implicative matrix” is based upon the notion of a “natural conditional” defined in Tomova (Rep Math Log 47:173–182, 2012).S

Immunological assays for chemokine detection in in-vitro culture of CNS cells

Herein we review the various methods currently in use for determining the expression of chemokines by CNS cells in vitro. Chemokine detection assays are used in conjuction with one another to provide a comprehensive, biologically relevant assessment of the chemokines which is necessary for correct data interpretation of a specific observed biological effect. The methods described include bioassays for soluble chemokine receptors, RNA extraction, RT-PCR, Real - time quantitative PCR, gene array analysis, northern blot analysis, Ribonuclease Protection assay, Flow cytometry, ELISPOT, western blot analysis, and ELISA. No single method of analysis meets the criteria for a comprehensive, biologically relevant assessment of the chemokines, therefore more than one assay might be necessary for correct data interpretation, a choice that is based on development of a scientific rationale for the method with emphasis on the reliability and relevance of the method

Biodiversity on Broadway - Enigmatic Diversity of the Societies of Ants (Formicidae) on the Streets of New York City

Each year, a larger proportion of the Earth's surface is urbanized, and a larger proportion of the people on Earth lives in those urban areas. The everyday nature, however, that humans encounter in cities remains poorly understood. Here, we consider perhaps the most urban green habitat, street medians. We sampled ants from forty-four medians along three boulevards in New York City and examined how median properties affect the abundance and species richness of native and introduced ants found on them. Ant species richness varied among streets and increased with area but was independent of the other median attributes measured. Ant assemblages were highly nested, with three numerically dominant species present at all medians and additional species present at a subset of medians. The most common ant species were the introduced Pavement ant (Tetramorium caespitum) and the native Thief ant (Solenopsis molesta) and Cornfield ant (Lasius neoniger). The common introduced species on the medians responded differently to natural and disturbed elements of medians. Tetramorium caespitum was most abundant in small medians, with the greatest edge/area ratio, particularly if those medians had few trees, whereas Nylanderia flavipes was most abundant in the largest medians, particularly if they had more trees. Many of the species encountered in Manhattan were similar to those found in other large North American cities, such that a relatively small subset of ant species probably represent most of the encounters humans have with ants in North America

Vowel reduction in word-final position by early and late Spanish-English bilinguals

Vowel reduction is a prominent feature of American English, as well as other stress-timed languages. As a phonological process, vowel reduction neutralizes multiple vowel quality contrasts in unstressed syllables. For bilinguals whose native language is not characterized by large spectral and durational differences between tonic and atonic vowels, systematically reducing unstressed vowels to the central vowel space can be problematic. Failure to maintain this pattern of stressed-unstressed syllables in American English is one key element that contributes to a ?foreign accent? in second language speakers. Reduced vowels, or ?schwas,? have also been identified as particularly vulnerable to the co-articulatory effects of adjacent consonants. The current study examined the effects of adjacent sounds on the spectral and temporal qualities of schwa in word-final position. Three groups of English-speaking adults were tested: Miami-based monolingual English speakers, early Spanish-English bilinguals, and late Spanish-English bilinguals. Subjects performed a reading task to examine their schwa productions in fluent speech when schwas were preceded by consonants from various points of articulation. Results indicated that monolingual English and late Spanish-English bilingual groups produced targeted vowel qualities for schwa, whereas early Spanish-English bilinguals lacked homogeneity in their vowel productions. This extends prior claims that schwa is targetless for F2 position for native speakers to highly-proficient bilingual speakers. Though spectral qualities lacked homogeneity for early Spanish-English bilinguals, early bilinguals produced schwas with near native-like vowel duration. In contrast, late bilinguals produced schwas with significantly longer durations than English monolinguals or early Spanish-English bilinguals. Our results suggest that the temporal properties of a language are better integrated into second language phonologies than spectral qualities. Finally, we examined the role of nonstructural variables (e.g. linguistic history measures) in predicting native-like vowel duration. These factors included: Age of L2 learning, amount of L1 use, and self-reported bilingual dominance. Our results suggested that different sociolinguistic factors predicted native-like reduced vowel duration than predicted native-like vowel qualities across multiple phonetic environments