bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of cytochrome P450 inhibition and induction potential of lupeol and betulin in rat liver microsomes
Authors: Seervi Madhav , Lotankar Shweta , Barbar Shrikant , Sathaye Sadhana
Published: March 2016

Background: Lupeol and betulin are triterpenoids that are majorly found in dietary substances. The aim of present study was to investigate the inhibition and induction potential of lupeol and betulin on cytochrome P450 (CYP)1A2, CYP2C11, CYP2D6 and CYP3A2 activities in rat liver microsomes.

Methods: The inhibition and induction studies were conducted using ethoxy resorufin-O-deethylase (CYP1A2), tolbutamide hydroxylase (CYP2C9), and midazolam hydroxylase (CYP3A4) activity assays. In vitro inhibition study was evaluated by incubating lupeol and betulin (1, 3, 10, 30 and 100 μM) with rat liver microsomes, and the metabolite formation was analyzed by high-performance liquid chromatography. The induction study was conducted by administering lupeol (20 mg/kg) and betulin (50 mg/kg) intraperitoneally for 14 days to rats followed by liver isolation and microsome preparation.

Results: The IC50 values in inhibition studies were found to be 59.42 μM (CYP1A2), >100 μM (CYP2C11, CYP2D6, CYP3A2) for lupeol, 52.24 μM (CYP1A2), and >100 μM (CYP2C9, CYP2D6, CYP3A2) for betulin. There was no significant modification observed in the CYP450 isoforms, indicating neither inhibition nor induction potential of lupeol and betulin.

Conclusions: Lupeol and betulin have very low propensity to interact with CYP enzyme, suggesting no CYP inhibitory and inducing potential in rat liver microsomes.
Axisymmetric mixed convective MHD flow over a slender cylinder in the presence of chemically reaction
Authors: Prasad K.V. , Vaidya H. , Vajravelu K. , Datti P.S. , Umesh V.
Published: March 2016

The present analysis is focused on the study of the magnetic effect on coupled heat and mass transfer by mixed convection boundary layer flow over a slender cylinder in the presence of a chemical reaction. The buoyancy effect due to thermal diffusion and species diffusion is investigated. Employing suitable similarity transformations, the governing equations are transformed into a system of coupled non-linear ordinary differential equations and are solved numerically via the implicit, iterative, second order finite difference method. The numerical results obtained are compared with the available results in the literature for some special cases and the results are found to be in excellent agreement. The velocity, temperature, and the concentration profiles are presented graphically and analyzed for several sets of the pertinent parameters. The pooled effect of the thermal and mass Grashof number is to enhance the velocity and is quite the opposite for temperature and the concentration fields.
Mass transfer effects on an unsteady MHD free convective flow of an incompressible viscous dissipative fluid past an infinite vertical porous plate
Authors: Prabhakar Reddy B.
Published: March 2016

In this paper, a numerical solution of mass transfer effects on an unsteady free convection flow of an incompressible electrically conducting viscous dissipative fluid past an infinite vertical porous plate under the influence of a uniform magnetic field considered normal to the plate has been obtained. The non-dimensional governing equations for this investigation are solved numerically by using the Ritz finite element method. The effects of flow parameters on the velocity, temperature and concentration fields are presented through the graphs and numerical data for the skin-friction, Nusselt and Sherwood numbers are presented in tables and then discussed.
Thimerosal exposure and increased risk for diagnosed tic disorder in the United States: a case-control study
Authors: Geier David A. , Kern Janet K. , Hooker Brian S. , King Paul G. , Sykes Lisa K. , Homme Kristin G. , Geier Mark R.
Published: March 2016

A hypothesis testing, case-control study evaluated automated medical records for exposure to organic-Hg from Thimerosal-containing hepatitis B vaccines (TM-HepB) administered at specific intervals in the first six-months-of-life among cases diagnosed with a tic disorder (TD) or cerebral degeneration (CD) (an outcome not biologically plausibly linked to TM exposure) in comparison to controls; both cases and controls were continuously enrolled from birth (born from 1991–2000) within the Vaccine Safety Datalink (VSD) database. TD cases were significantly more likely than controls to have received increased organic-Hg from TM-HepB administered within the first month-of-life (odds ratio (OR)=1.59, p<0.00001), first two-months-of-life (OR=1.59, p<0.00001), and first six-months-of-life (OR=2.97, p<0.00001). Male TD cases were significantly more likely than male controls to have received increased organic-Hg from TM-HepB administered within the first month-of-life (OR =1.65, p<0.0001), first two-months-of-life (OR=1.64, p<0.0001), and first six months-of-life (OR=2.47, p<0.05), where as female TD were significantly more likely than female controls to have received increased organic-Hg from TM-HepB administered within the first six-months-of-life (OR=4.97, p<0.05). By contrast, CD cases were no more likely than controls to have received increased organic-Hg exposure from TM-HepB administered at any period studied within the first six-months-of-life. Although routine childhood vaccination is considered an important public health tool to combat infectious diseases, the present study associates increasing organic-Hg exposure from TM-HepB and the subsequent risk of a TD diagnosis.
Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats
Authors: Lakhera Abhijeet , Ganeshpurkar Aditya , Bansal Divya , Dubey Nazneen
Published: March 2016

Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies.

Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.
Local salt substitutes “Obu-otoyo” activate acetylcholinesterase and butyrylcholinesterase and induce lipid peroxidation in rat brain
Authors: Akinyemi Ayodele J. , Oboh Ganiyu , Ademiluyi Adedayo O.
Published: March 2016

Evidence has shown that ingestion of heavy metals can lead to neurodegenerative diseases. This study aimed to investigate the neurotoxic potential of salt substitutes (Obu-Otoyo); salt A (made by burning palm kernel shaft then soaked in water overnight and the extract from the resulting residue is used as the salt substitute) and salt B (an unrefined salt mined from a local site at Ilobu town, Osun-State, Nigeria) by assessing their effect on some key enzymes linked with neurodegenerative disease [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities] as well as on malondialdehyde (MDA) content of the rat brain. Salt substitutes were fed to normal rats as dietary inclusion at doses of 0.5 and 1.0% for 30 days. Thereafter, the effect of the salt substitutes on AChE and BChE activities as well as on MDA level in the rat brain was determined. The results revealed that the salt substitutes caused a significant (p<0.05) increase in both AChE and BChE activity and also induced lipid peroxidation in the brain of rats in vivo as well as under in vitro condition in a dose-dependent manner. The effect of the salt substitutes on AChE and BChE activities could be attributed to the presence of some toxic heavy metals. Therefore, the ability of the salt substitutes to induce lipid peroxidation and activate AChE and BChE activities could provide some possible mechanism for their neurotoxic effect.
Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats
Authors: Samarghandian Saeed , Azimi-Nezhad Mohsen , Shabestari Mahmoud M. , Azad Farahzad Jabbari , Farkhondeh Tahereh , Bafandeh Fereshteh
Published: March 2016

Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities. The present study was designed to elucidate the possible association between chronic exposure to Cd concentration and alterations in plasma lipid, lipoprotein, and oxidative stress indices in rats. Sixteen male rats were assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group obtained drinking water containing cadmium chloride (CdCl2) in the concentration of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental period, blood samples were obtained to determine the changes of serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH), malondialdehyde (MDA) and also serum Cd contents. The results of the present study indicated that Cd administration significantly increased the serum levels of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In conclusion, evidence is presented that chronic exposure to low Cd concentration can adversely affect the lipid and lipoprotein profile via lipid peroxidation.
Revisiting the typology of pragmatic interpretations
Authors: Ariel Mira
Published: March 2016

Pragmatic inferences are essential to understanding speakers’ communicative intentions. I here revisit the typology of pragmatic inferences and minimally revise it by incorporating into it additional distinctions. Inspired by Recanati’s (
The negotiation of discourse relations in context: Co-constructing degrees of overtness
Authors: Maier Robert M. , Hofmockel Carolin , Fetzer Anita
Published: March 2016

This paper examines the linguistic realization of discourse relations in the discourse genre of commentary. Based on a “bare” source text from which all extraclausal constituents had been removed, the linguistic realization of discourse relations is compared across three dyadically co-constructed experimental texts. The methodological framework integrates Segmented Discourse Representation Theory with functional grammar and psycholinguistic models of discourse processing, and describes discourse relations (DRs) that tend to be indexed implicitly only, that is, via intraclausal cues, and others that tend to be indexed with a mix of intra- and extraclausal cues. Continuation and Result; Continuation and Elaboration; and Elaboration, Explanation, and Background show some overlap in their definitions, and that is why their realizations may remain vague unless they are supplemented with extraclausal cues. Salience can account for the overspecifications observed, while underspecifications may be accounted for in terms of cognitive economy.
Performance Analysis of DPSK-OCDMA System for Optical Access Network
Authors: Islam Monirul , Ahmed N. , Aljunid S. A. , Ali Sharafat , Sayeed S. , Sabri Naseer
Published: March 2016

In this research, the performance of optical code division multiple access (OCDMA) using differential phase shift keying (DPSK) has been compared with OCDMA On-Off Keying (OOK). This comparison took place in terms of bit error rate (BER) and receiver power where two bit rates (155 Mbps and 622 Mbps) have been used for this analysis. Using of OptiSystem 7.0 simulation, comparing eye diagram and optical spectrum alongside with BER and Rx power. It is found that OCDMA-DPSK performs better in comparison to OCDMA-OOK. The performance analysis also provides parameter for designing and development of an OCDMA system for optical access network using DPSK.
More than one way to skin a thyroid. Managing pediatric hypothyroidism with weekly intramuscular levothyroxine
Authors: Alba Patria , Mitre Naim , Feldt Max
Published: March 2016

Oral levothyroxine (L-T4) supplementation is usually an effective therapy in pediatric hypothyroidism, except in patients with malabsorption or pseudomalabsorption. In these cases, parenteral L-T4 may be required, but there is a paucity of information about this delivery method in the pediatric population.

We present three cases of pediatric patients with primary hypothryoidism unresponsive to oral L-T4 that were successfully treated with intramuscular (IM) L-T4.

This is the first pediatric case series of successful IM L-T4 therapy in refractory primary hypothyroidism. Our case series demonstrates that once weekly IM L-T4 dosing may be a safe and well tolerated treatment regimen for pediatric patients.
Comparison between capillary glucose measured with a Contour glucometer and plasma glucose in a population survey
Authors: Stauffer Florine , Viswanathan Bharathi , Jean Maygane , Kinabo Prosper , Bovet Pascal
Published: March 2016

Background: Capillary glucose (CG) measured with point-of-care glucometers can provide useful approximation of plasma glucose (PG) in selected circumstances but the validity of measurements has been adequately assessed only for a few glucometers.

Methods: We assessed the difference between CG measured with a glucometer (Contour Ascensia, Bayer) and PG measured with a standard laboratory method in participants to a population-based cardiovascular survey in the Seychelles (sample size 1227).

Results: CG correlated well with PG (r=0.94; p<0.001). The overall difference between PG and CG was –0.55 mmol/L for PG <4.0 mmol/L (n=19; 95% CI –0.92; –0.18); 0.14 mmol/L for PG 4.0–4.9 (n=344; 95% CI 0.08–0.20) and increased according to PG up to 1.64 mmol/L for PG >9.0 mmol/L (n=68; 95% CI 1.36; 1.91). The prevalence of diabetes in the study sample was 29% lower with CG than with PG (8.6% vs. 12.1%) but this bias could be corrected by analytical re-calibration.

Conclusions: CG underestimated PG, although the bias was small among persons with low glycemia. This systematic difference may bear little significance when the purpose is to simply monitor blood glucose but has large impact on prevalence estimates at the population level if CG values are not adequately calibrated.
Quality control and validation in flow cytometry
Authors: Dorn-Beineke Alexandra , Sack Ulrich
Published: March 2016

Diagnostic flow cytometry has been established in laboratory diagnostics as an indispensable, deeply specialized method. Because of the special needs of the analysis in vital cells, the introduction and maintenance of quality management systems stays a challenge. Meanwhile, experience has been collected for quality controls and validation in diagnostic flow cytometry. This will be summarized in this article. The focus will be on the relevant rules and regulations for diagnostic laboratories and the associated requirements for medical diagnostics, as well the guidelines of the German Medical Association, Bundesärztekammer, (RiliBÄK) and in particular the accreditation according to DIN EN ISO 15189. In detail, factors influencing flow cytometry analyses, strategies for the standardization and harmonization in flow cytometry, and possibilities for verification and validation in the flow cytometry laboratory are given. A summary of the most frequent quality problems rounds up this overview.
Discourse of persuasion: a preliminary study of the use of metadiscourse in policy documents
Authors: Ho Victor
Published: March 2016

The Hong Kong Special Administrative Region (HKSAR) government has proposed a number of reform initiatives in different policy areas since its establishment in 1997. This paper explores and discusses the HKSAR government’s discursive attempt to persuade the people of Hong Kong to accept two education policy reforms it has proposed. Adopting a corpus-based approach and drawing upon the construct of metadiscourse as the method of inquiry in the study, the author found that the HKSAR government had appealed to logos, ethos, and pathos with metadiscourse in the policy reform discourse in actualizing its persuasive attempts. The present study represents a modest attempt to analyze the policy document genre from a metadiscursive perspective and to inform writers of the genre of the possible ways to textualize the three means of persuasion – logos, ethos, and pathos – who will then be more aware of the resources that they can use to enhance the persuasiveness of their writing.
The impact of recurrent propositions on readers’ perceptions of gist: A study of hard news
Authors: Yuan ke Li
Published: March 2016

Employing a systemic functional approach to the analysis of cohesive elements, this paper investigates the impact of recurrent propositions in texts on readers’ perceptions of their gist in a study of hard news and their summaries written by competent readers. The results show that the number of times propositions recur in news does not correspond to readers’ perceptions of their degrees of importance to the gist of news in which they occur, pointing to the limited role of repetition in identifying important propositions. This study also shows that two factors, namely the textual positions of propositions occurring in news, and the relationships between different propositions, played an important part when readers examined whether propositions were important to the gist of news in which they occur. The study complements the corpus-driven approaches to phraseology by extending the scope of phraseological combinations to include paraphrases and other semantic relations in the identification of identical and similar propositions recurring in individual texts.
The Thermodynamic Functions in Curved Space of Neutron Star
Authors: Hussein N.A. , Eisa D.A. , Sayed E.G.
Published: March 2016

The aim of this article is to calculate the thermodynamic functions of a neutron star in curved space. We obtained equation of state (EOS) and the excess free energy for a neutron star in curved space up to order n
4, where n is the density of particles.
Long-chain alkyl-substituted gentisic acid and benzoquinone derivatives from the root of Micronychia tsiramiramy (Anacardiaceae)
Authors: Razakarivony Andrianambinina A. , Lenta Bruno N. , Andriamihaja Bakolinirina , Michalek Carmela , Razanamahefa Bakonirina , Razafimahefa Dorothée R. , Rakotondramanga Maonja Finaritra , Randrianasolo Rivoarison , Lannang Alain Méli , Randriamiaramisaina Ralinandrianina , Boyom Fekam F. , Rosenthal Philip J. , Sewald Norbert
Published: March 2016

A new gentisic acid derivative named micronyc acid (1) and a new 1,4-benzoquinone derivative named micronone (2) have been isolated from the root of Micronychia tsiramiramy together with the known compounds gallic acid (3), methyl gallate (4), moronic acid (5), masticadienolic acid (6), and masticadienediol (7). The structures of 1 and 2 were established using MS and NMR. Compound 1 was tested for antiplasmodial activity in vitro against the chloroquine-resistant strain Plasmodium falciparum W2 and displayed moderate antiplasmodial activity in vitro with an IC50 value of 25.6 μ
m. Compounds 1 and its acetyl derivative 1a were also tested for their cytotoxicity against the human cervix carcinoma cell line KB-3-1 and still showed moderate activity.
Hydroalumination and hydrogallation of an aryl-chloro-dialkynylsilane: Si–Cl bond activation by intramolecular Al–Cl and Ga–Cl interactions
Authors: Uhl Werner , Kappelt Benedikt , Kappelt Frederik , Bohnemann Jörg , Layh Marcus
Published: March 2016

The chlorine functionalized dialkynylsilane (4-
t
Bu-C6H4)(Cl)Si(C≡C-
t
Bu)2 (3) reacted with equimolar quantities of H–Al
t
Bu2 or H–Ga
t
Bu2 by hydrometallation of a C≡C triple bond and formation of mixed alkenyl-alkynylsilanes (4 and 5) in which the Si and Lewis acidic metal atoms adopt geminal positions at the α-C atoms of the alkenyl groups. Intramolecular M···Cl interactions (M=Al, Ga) afforded four-membered SiCMCl heterocycles which in comparison with 3 had significantly lengthened Si–Cl bonds. Dual hydrometallation of 3 was only observed for H–Ga
t
Bu2. One Ga atom of the product (6) was coordinated by the silicon-bound Cl atom, while the second one showed an interaction with the aromatic ring of the tert-butyl-phenyl group. Treatment of the aluminium compound 4 with two equivalents of H–Ga
t
Bu2 afforded a Si–H bond by Cl-H exchange and release of Cl–Al
t
Bu2. The resulting silane (7) has the Si atom and two Ga atoms bridged by the α-C atoms of two vinyl groups. The specific functionality of 4 caused a remarkable reactivity. Phenyl isocyanate reacted by the formal insertion into the Al–C(vinyl) and the activated Si–Cl bonds and resulted in the formation of a C–C bond. The product (8) has a SiC2N heterocycle with an Si–N bond and exocyclic C=C and C=O double bonds. The keto group is coordinated to a Cl–Al
t
Bu2 molecule, which was formed by the shift of the Cl atom from silicon to aluminium.
Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity
Authors: Ekman Matthias , Fiebach Christian J. , Melzer Corina , Tittgemeyer Marc , Derrfuss Jan
Published: March 2016

The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs considerably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. In contrast, in Study 2, where participants were required to maintain working memory items without updating, only the connectivity of the direct pathway was predictive of individual WMC. Our results suggest an important dissociation in the circuitry connecting frontal and parietal regions, where direct frontoparietal connections might support storage and maintenance, whereas subcortically mediated connections support the flexible updating of working memory content.

SIGNIFICANCE STATEMENTUsing diffusion MRI and network analysis, we found that the capacity of healthy individuals to temporally maintain information in working memory was related to a cortical pathway connecting frontal and parietal regions. The updating of working memory content, on the other hand, additionally involved a subcortical pathway connecting frontal and parietal regions via thalamus and basal ganglia. These results suggest that the two anatomical pathways serve different functional roles for working memory.
Human Choice Strategy Varies with Anatomical Projections from Ventromedial Prefrontal Cortex to Medial Striatum
Authors: Piray Payam , Toni Ivan , Cools Roshan
Published: March 2016

Two distinct systems, goal-directed and habitual, support decision making. It has recently been hypothesized that this distinction may arise from two computational mechanisms, model-based and model-free reinforcement learning, neuronally implemented in frontostriatal circuits involved in learning and behavioral control. Here, we test whether the relative strength of anatomical connectivity within frontostriatal circuits accounts for variation in human individuals' reliance on model-based and model-free control. This hypothesis was tested by combining diffusion tensor imaging with a multistep decision task known to distinguish model-based and model-free control in humans. We found large interindividual differences in the degree of model-based control, and those differences are predicted by the structural integrity of white-matter tracts from the ventromedial prefrontal cortex to the medial striatum. Furthermore, an analysis based on masking out of bottom-up tracts suggests that this effect is driven by top-down influences from ventromedial prefrontal cortex to medial striatum. Our findings indicate that individuals with stronger afferences from the ventromedial prefrontal cortex to the medial striatum are more likely to rely on a model-based strategy to control their instrumental actions. These findings suggest a mechanism for instrumental action control through which medial striatum determines, at least partly, the relative contribution of model-based and model-free systems during decision-making according to top-down model-based information from the ventromedial prefrontal cortex. These findings have important implications for understanding the neural circuitry that might be susceptible to pathological computational processes in impulsive/compulsive psychiatric disorders.

SIGNIFICANCE STATEMENTScholars from several disciplines have long been interested in the neural mechanisms of decision-making. An influential suggestion has structured decision-making into a flexible but expensive model-based system, and a more rapid but also more rigid model-free system. Here, we show that anatomical properties of the connections between frontal and striatal regions predict the use of a model-based system when individuals make decisions. Individuals with stronger top-down connectivity from the ventromedial prefrontal cortex to the medial striatum were more likely to rely on a model-based strategy during decision-making, suggesting that the ventromedial prefrontal cortex biases a striatal balance between model-based and model-free control. These findings qualify the neural implementation of decision-making computations and open the way for understanding decision-making pathologies.
Absence of Prenatal Forebrain Defects in the Dp(16)1Yey/+ Mouse Model of Down Syndrome
Authors: Goodliffe Joseph W. , Olmos-Serrano Jose Luis , Aziz Nadine M. , Pennings Jeroen L.A. , Guedj Faycal , Bianchi Diana W. , Haydar Tarik F.
Published: March 2016

Studies in humans with Down syndrome (DS) show that alterations in fetal brain development are followed by postnatal deficits in neuronal numbers, synaptic plasticity, and cognitive and motor function. This same progression is replicated in several mouse models of DS. Dp(16)1Yey/+ (hereafter called Dp16) is a recently developed mouse model of DS in which the entire region of mouse chromosome 16 that is homologous to human chromosome 21 has been triplicated. As such, Dp16 mice may more closely reproduce neurodevelopmental changes occurring in humans with DS. Here, we present the first comprehensive cellular and behavioral study of the Dp16 forebrain from embryonic to adult stages. Unexpectedly, our results demonstrate that Dp16 mice do not have prenatal brain defects previously reported in human fetal neocortex and in the developing forebrains of other mouse models, including microcephaly, reduced neurogenesis, and abnormal cell proliferation. Nevertheless, we found impairments in postnatal developmental milestones, fewer inhibitory forebrain neurons, and deficits in motor and cognitive performance in Dp16 mice. Therefore, although this new model does not express prenatal morphological phenotypes associated with DS, abnormalities in the postnatal period appear sufficient to produce significant cognitive deficits in Dp16.

SIGNIFICANCE STATEMENTDown syndrome (DS) leads to intellectual disability. Several mouse models have increased our understanding of the neuropathology of DS and are currently being used to test therapeutic strategies. A new mouse model that contains an expanded number of DS-related genes, known as Dp(16)1Yey/+ (Dp16), has been generated recently. We sought to determine whether the extended triplication creates a better phenocopy of DS-related brain pathologies. We measured embryonic development, forebrain maturation, and perinatal/adult behavior and revealed an absence of prenatal phenotypes in Dp16 fetal brain, but specific cellular and behavioral deficits after the first 2 postnatal weeks. These results uncover important differences in prenatal phenotype between Dp16 animals and humans with DS and other DS mouse models.
Pitch-Responsive Cortical Regions in Congenital Amusia
Authors: Norman-Haignere Sam V. , Albouy Philippe , Caclin Anne , McDermott Josh H. , Kanwisher Nancy G. , Tillmann Barbara
Published: March 2016

Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work.

SIGNIFICANCE STATEMENTThe neural causes of congenital amusia, a lifelong deficit in pitch and music perception, are not fully understood. We tested the hypothesis that amusia is due to abnormalities in brain regions that respond selectively to sounds with a pitch in normal listeners. Surprisingly, amusic individuals exhibited pitch-responsive regions that were similar to normal-hearing controls in extent, selectivity, and anatomical location. We discuss how our results inform current debates on the neural basis of amusia and how the ability to identify pitch-responsive regions in amusic subjects will make it possible to ask more precise questions about their role in amusic deficits.
Attention Strongly Modulates Reliability of Neural Responses to Naturalistic Narrative Stimuli
Authors: Ki Jason J. , Kelly Simon P. , Parra Lucas C.
Published: March 2016

Attentional engagement is a major determinant of how effectively we gather information through our senses. Alongside the sheer growth in the amount and variety of information content that we are presented with through modern media, there is increased variability in the degree to which we “absorb” that information. Traditional research on attention has illuminated the basic principles of sensory selection to isolated features or locations, but it provides little insight into the neural underpinnings of our attentional engagement with modern naturalistic content. Here, we show in human subjects that the reliability of an individual's neural responses with respect to a larger group provides a highly robust index of the level of attentional engagement with a naturalistic narrative stimulus. Specifically, fast electroencephalographic evoked responses were more strongly correlated across subjects when naturally attending to auditory or audiovisual narratives than when attention was directed inward to a mental arithmetic task during stimulus presentation. This effect was strongest for audiovisual stimuli with a cohesive narrative and greatly reduced for speech stimuli lacking meaning. For compelling audiovisual narratives, the effect is remarkably strong, allowing perfect discrimination between attentional state across individuals. Control experiments rule out possible confounds related to altered eye movement trajectories or order of presentation. We conclude that reliability of evoked activity reproduced across subjects viewing the same movie is highly sensitive to the attentional state of the viewer and listener, which is aided by a cohesive narrative.

SIGNIFICANCE STATEMENTModern technology has brought about a monumental surge in the availability of information. There is a pressing need for ways to measure and characterize attentional engagement and understand the causes of its waxing and waning in natural settings. The present study demonstrates that the degree of an individual's attentional engagement with naturalistic narrative stimuli is strongly predicted by the degree of similarity of his/her neural responses to a wider group. The effect is so strong that it enables perfect classification of attentional state across individuals for some narrative stimuli. As modern information content continues to diversify, such direct neural metrics will become increasingly important to manage and evaluate its effects on both the healthy and disordered human brain.
Reactivation of Reward-Related Patterns from Single Past Episodes Supports Memory-Based Decision Making
Authors: Wimmer G. Elliott , Büchel Christian
Published: March 2016

Rewarding experiences exert a strong influence on later decision making. While decades of neuroscience research have shown how reinforcement gradually shapes preferences, decisions are often influenced by single past experiences. Surprisingly, relatively little is known about the influence of single learning episodes. Although recent work has proposed a role for episodes in decision making, it is largely unknown whether and how episodic experiences contribute to value-based decision making and how the values of single episodes are represented in the brain. In multiple behavioral experiments and an fMRI experiment, we tested whether and how rewarding episodes could support later decision making. Participants experienced episodes of high reward or low reward in conjunction with incidental, trial-unique neutral pictures. In a surprise test phase, we found that participants could indeed remember the associated level of reward, as evidenced by accurate source memory for value and preferences to re-engage with rewarded objects. Further, in a separate experiment, we found that high-reward objects shown as primes before a gambling task increased financial risk taking. Neurally, re-exposure to objects in the test phase led to significant reactivation of reward-related patterns. Importantly, individual variability in the strength of reactivation predicted value memory performance. Our results provide a novel demonstration that affect-related neural patterns are reactivated during later experience. Reactivation of value information represents a mechanism by which memory can guide decision making.

SIGNIFICANCE STATEMENTRewarding and aversive experiences exert a strong influence on later decision making. Although much is known about how many associations between stimuli and reward shapes preferences, decisions are often supported by the value of single past experiences. Surprisingly, relatively little is known about how episodic experiences influence later behavior. In experiments using monetary reward anticipation in conjunction with incidental objects, we found that later behavior was indeed influenced by the value incidentally associated with objects. Critically, neural patterns related to reward experiences were re-expressed on later exposure and reactivation correlated with behavioral performance. Our results suggest a mechanism by which good and bad episodes from daily life can guide later decision making.
Cyclic AMP and Polyamines Overcome Inhibition by Myelin-Associated Glycoprotein through eIF5A-Mediated Increases in p35 Expression and Activation of Cdk5
Authors: He Huifang , Deng Kangwen , Siddiq Mustafa M. , Pyie Aung , Mellado Wilfredo , Hannila Sari S. , Filbin Marie T.
Published: March 2016

Inhibitory molecules associated with CNS myelin, such as myelin-associated glycoprotein (MAG), represent major obstacles to axonal regeneration following CNS injury. Our laboratory has shown that elevating levels of intracellular cAMP, via application of the nonhydrolyzable analog dibutyryl cAMP (dbcAMP), can block the inhibitory effects of MAG and myelin. We have also shown that elevation of cAMP results in upregulation of arginase I and increased polyamine synthesis. Treatment with putrescine or spermidine blocks myelin-mediated inhibition of neurite outgrowth, but the mechanism underlying this effect has not yet been elucidated. Here we show that cyclin-dependent kinase 5 (Cdk5) is required for dbcAMP and putrescine to overcome MAG-mediated inhibition. The ability of dbcAMP and putrescine to overcome inhibition by MAG is abolished in the presence of roscovitine, a Cdk inhibitor that has greater selectivity for Cdk5, and expression of dominant negative Cdk5 abolishes the ability of dbcAMP or putrescine to enhance neurite outgrowth in the presence of MAG. Importantly, dbcAMP and putrescine increase expression of p35, the neuron-specific activator of Cdk5, and rat DRG neurons transduced with HSV overexpressing p35 can overcome inhibition by MAG. The upregulation of p35 by putrescine is also reflected in increased localization of p35 to neurites and growth cones. Last, we show that putrescine upregulates p35 expression by serving as a substrate for hypusine modification of eIF5A, and that this hypusination is necessary for putrescine's ability to overcome inhibition by MAG. Our findings reveal a previously unknown mechanism by which polyamines may encourage regeneration after CNS injury.

SIGNIFICANCE STATEMENTThis study describes a novel mechanism for the activation of Cdk5 in neurons and a new role for Cdk5 in promoting axonal growth in the presence of myelin-associated inhibitors. We show that administration of the polyamine putrescine leads to hypusination of the translation initiation factor eIF5A, increased translation of p35, and activation of Cdk5 in cultured cerebellar neurons, and that each of these events is required for putrescine's ability to overcome inhibition by myelin-associated glycoprotein. These findings have implications for the development of new treatments for spinal cord and traumatic brain injury and provide new insight into the functions of eIF5A and Cdk5 in the nervous system.
Owen Biddle and Philadelphia's Real Estate Market, 1798–1806
Authors: Lucey Conor
Published: March 2016

The Philadelphia architect and master builder Owen Biddle (1774–1806) contributed to the making of some of the early Republic's most important buildings and is best known as the author of one of the first American-authored architectural books. During the course of his relatively brief career, Biddle's achievements in architecture and theory were profoundly shaped by Philadelphia's distinctive, Quaker-influenced economic and artistic culture. Focusing on two hitherto unknown row houses built by Biddle between 1798 and 1801, Conor Lucey reveals for the first time the business and property interests of this important if enigmatic figure. Viewing Biddle's work against the socioeconomic backdrop of Federal-era Philadelphia, and drawing on previously unexplored archival material, Owen Biddle and Philadelphia's Real Estate Market, 1798–1806 situates Biddle's real estate ventures within the context of the city's early nineteenth-century building world. This study of Biddle's career as builder-developer expands our knowledge of his professional life and our understanding of the formation of his ideas.
Surveying, Interpreting, and Designing: The Multiple Essence of a Sixteenth-Century Drawing
Authors: Nuti Lucia
Published: March 2016

In Surveying, Interpreting, and Designing: The Multiple Essence of a Sixteenth-Century Drawing, Lucia Nuti examines Uffizi drawing 7950 A, an unfinished representation of Pisa attributed to Giuliano da Sangallo. First addressing problems of authorship and dating, Nuti analyzes the main features and contents of the drawing, which she concludes cannot be labeled a survey or ground plan, and draws insights regarding a more complex issue, the multiple nature of the artifact. This unique sheet, far from being the visual record of a measured urban space, is a personal record that reflects Giuliano's approach to design as well as the meaning of the process of drawing. At the beginning of the sixteenth century, drawing was developing as a medium for architectural communication, and the borders between surveying, interpreting, and designing were blurred.
Increased plasma leptin attenuates adaptive metabolism in early lactating dairy cows
Authors: Ehrhardt Richard A , Foskolos Andreas , Giesy Sarah L , Wesolowski Stephanie R , Krumm Christopher S , Butler W Ronald , Quirk Susan M , Waldron Matthew R , Boisclair Yves R
Published: March 2016

Mammals meet the increased nutritional demands of lactation through a combination of increased feed intake and a collection of adaptations known as adaptive metabolism (e.g., glucose sparing via insulin resistance, mobilization of endogenous reserves, and increased metabolic efficiency via reduced thyroid hormones). In the modern dairy cow, adaptive metabolism predominates over increased feed intake at the onset of lactation and develops concurrently with a reduction in plasma leptin. To address the role of leptin in the adaptive metabolism of early lactation, we asked which adaptations could be countered by a constant 96-h intravenous infusion of human leptin (hLeptin) starting on day 8 of lactation. Compared to saline infusion (Control), hLeptin did not alter energy intake or milk energy output but caused a modest increase in body weight loss. hLeptin reduced plasma glucose by 9% and hepatic glycogen content by 73%, and these effects were associated with a 17% increase in glucose disposal during an insulin tolerance test. hLeptin attenuated the accumulation of triglyceride in the liver by 28% in the absence of effects on plasma levels of the anti-lipolytic hormone insulin or plasma levels of free fatty acids, a marker of lipid mobilization from adipose tissue. Finally, hLeptin increased the plasma concentrations of T4and T3by nearly 50% without affecting other neurally regulated hormones (i.e., cortisol and luteinizing hormone (LH)). Overall these data implicate the periparturient reduction in plasma leptin as one of the signals promoting conservation of glucose and energy at the onset of lactation in the energy-deficient dairy cow.
COMPARISON OF COFFEE SPECIES BY SENSORY PANEL AND ELECTRONIC NOSE
Authors: Vietoris Vladimir , Zajác Peter , Čapla Jozef , Mendelová Andrea , Križanová Kamila , Benešová Lucia
Published: March 2016

The objective of a comparative study was to investigate the relationship between the sensory assessment of the varietal coffee samples and their aromatic profile measured using an electronic nose. Sensory analysis plays a very important role in the evaluation of food especially in the evaluation of plant products (coffee included). Sensory assessor's role is to assess the taste, smell, texture and visual attributes of the product. Equally useful in the objective evaluation of foods and their flavor profile appears to be an electronic nose. The study showed that there is a difference in a flavored coffee varietal profile. This study was performed using techniques TDS for 15 seconds by naïve panel. Most of the coffee samples appeared bitter with sour aftertaste. Flavors of coffee are also often linked with its taste. The aim of measuring the electronic nose was thus instrumental to detect similarities between the seventh varietal coffees. The results showed that the similarity between human measurement panel and substantiating the electronic nose. Data were reduced using PCA techniques and most of the samples correspond to the same position at both assays.
PHYSICOCHEMICAL AND RHEOLOGICAL PROPERTIES OF DOOGH UNDER SPECIFIC FERMENTATION
Authors: Pakbin Babak , Mahmoudi Razzagh , Fakhri Omid
Published: March 2016

Fermented dairy products such as doogh are more nutritious than the natural milk from which they are made. In this study enhancing the viscosity of Doogh (Iranian yogurt drink) fermented by Leuconostoc mesenteroides under the optimum condition of exopolysaccharide (EPS) production including temperature of 25°C, agitation of 120 RPM and different sucrose contents from 0 to 2%, w/w, was investigated. Addition of sucrose was not influenced the rheological and sensory characteristics of Doogh samples before the fermentation significantly according to sensory and rheological analysis. The results of chemical, microbiological, viscosity, serum separation and sensory analysis showed that viscosity of Doogh increased corresponding to sucrose contents during the fermentation up to 10.01 cp with no change in the taste of the Doogh samples. Also, sensory analysis of consistency confirmed the viscosity results. Serum separation values of samples also showed enhancement in stability after the fermentation and finally, this special fermentation process contributed to enhancement in viscosity of Doogh as an edible suspension, with reasonable economic targets compared with other stabilizing methods.