julilili42/papers huggingface dataset:
<em>In vivo</em> Imaging of Intact <em>Drosophila</em> Larvae at Sub-cellular Resolution
2010-09-10

Recent improvements in optical imaging, genetically encoded fluorophores and genetic tools allowing efficient establishment of desired transgenic animal lines have enabled biological processes to be studied in the context of a living, and in some instances even behaving, organism. In this protocol we will describe how to anesthetize intact Drosophila larvae, using the volatile anesthetic desflurane, to follow the development and plasticity of synaptic populations at sub-cellular resolution. While other useful methods to anesthetize Drosophila melanogaster larvae have been previously described, the protocol presented herein demonstrates significant improvements due to the following combined key features: (1) A very high degree of anesthetization; even the heart beat is arrested allowing for lateral resolution of up to 150 nm, (2) a high survival rate of >90% per anesthetization cycle, permitting the recording of more than five time-points over a period of hours to days and (3) a high sensitivity enabling us in 2 instances to study the dynamics of proteins expressed at physiological levels. In detail, we were able to visualize the postsynaptic glutamate receptor subunit GluR-IIA expressed via the endogenous promoter in stable transgenic lines and the exon trap line FasII-GFP. (4) In contrast to other methods the larvae can be imaged not only alive, but also intact (i.e. non-dissected) allowing observation to occur over a number of days. The accompanying video details the function of individual parts of the in vivo imaging chamber, the correct mounting of the larvae, the anesthetization procedure, how to re-identify specific positions within a larva and the safe removal of the larvae from the imaging chamber.
<em>In vivo</em> Imaging of Intact <em>Drosophila</em> Larvae at Sub-cellular Resolution
2010-09-10

Recent improvements in optical imaging, genetically encoded fluorophores and genetic tools allowing efficient establishment of desired transgenic animal lines have enabled biological processes to be studied in the context of a living, and in some instances even behaving, organism. In this protocol we will describe how to anesthetize intact Drosophila larvae, using the volatile anesthetic desflurane, to follow the development and plasticity of synaptic populations at sub-cellular resolution1-3. While other useful methods to anesthetize Drosophila melanogaster larvae have been previously described4,5,6,7,8, the protocol presented herein demonstrates significant improvements due to the following combined key features: (1) A very high degree of anesthetization; even the heart beat is arrested allowing for lateral resolution of up to 150 nm1, (2) a high survival rate of > 90% per anesthetization cycle, permitting the recording of more than five time-points over a period of hours to days2 and (3) a high sensitivity enabling us in 2 instances to study the dynamics of proteins expressed at physiological levels. In detail, we were able to visualize the postsynaptic glutamate receptor subunit GluR-IIA expressed via the endogenous promoter1 in stable transgenic lines and the exon trap line FasII-GFP1. (4) In contrast to other methods4,7 the larvae can be imaged not only alive, but also intact (i.e. non-dissected) allowing observation to occur over a number of days1. The accompanying video details the function of individual parts of the in vivo imaging chamber2,3, the correct mounting of the larvae, the anesthetization procedure, how to re-identify specific positions within a larva and the safe removal of the larvae from the imaging chamber.
VISUALIZING CO-EVOLUTION OF INDIVIDUAL AND COLLECTIVE KNOWLEDGE
2010-09-12

This paper describes how processes of knowledge building with wikis may be visualized, citing the user-generated online encyclopedia Wikipedia as an example. The underlying theoretical basis is a framework for collaborative knowledge building with wikis that describes knowledge building as a co-evolution of individual and collective knowledge. These co-evolutionary processes may be visualized graphically, applying methods from social network analysis, especially those methods that take dynamic changes into account. For this purpose, we have undertaken to analyse, on the one hand, the temporal development of a Wikipedia article and related articles that are linked to this core article. On the other hand, we analysed the temporal development of those users who worked on these articles. The resulting graphics show an analogous process, both with regard to the articles that refer to the core article and to the users involved. These results provide empirical support for the co-evolution model.
Defect cost flow model
2010-09-12

Background. Software defect prediction has been one of the central topics of software engineering. Predicted defect counts have been used mainly to assess software quality and estimate the defect correction effort (DCE). However, in many cases these defect counts are not good indicators for DCE. Therefore, in this study DCE has been modeled from a different perspective. Defects originating from various development phases have different impact on the overall DCE, especially defects shifting from one phase to another. To reduce the DCE of a software product it is important to assess every development phase along with its specific characteristics and focus on the shift of defects over phases.
The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations
2010-09-13

Mitochondrial dysfunction is an early sign of many neurodegenerative diseases. Very recently, two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy). PINK1 kinase activity is needed for prompt and efficient Parkin recruitment to impaired mitochondria. PD-associated Parkin mutations interfere with the process of mitophagy at distinct steps. Here we show that whole mitochondria are turned over via macroautophagy. Moreover, disease-associated PINK1 mutations also compromise the selective degradation of depolarized mitochondria. This may be due to the decreased physical binding activity of PD-linked PINK1 mutations to Parkin. Thus, PINK1 mutations abrogate autophagy of impaired mitochondria upstream of Parkin. In addition to compromised PINK1 kinase activity, reduced binding of PINK1 to Parkin leads to failure in Parkin mitochondrial translocation, resulting in the accumulation of damaged mitochondria, which may contribute to disease pathogenesis.
Reaction of N-Nitro-benzotriazole with Nucleophiles
2010-09-13

N-Nitro-benzotriazole 1 reacts with various C-nucleophiles 2 in tetrahydrofuran at room temperature to afford o-nitramidophenylazo-compounds 3a–f and o-nitramidophenyl hydrazones 3g–l, respectively. Reaction of 1 with sodium azide in aqueous acetonitrile gives a reactive 2-azidophenylnitramide intermediate 4 which is trapped by Cu-catalyzed 1,3-dipolar cycloadition with phenyl acetylene to afford 1-o-nitramidophenyl-4-phenyl-1,2,3-triazole 5. Reaction of 1 with trimethylsilylcyanide affords 3-amino-benzo[e][1,2,4]triazine 6.
Relationships of Circulating Sex Hormone–Binding Globulin With Metabolic Traits in Humans
2010-09-14

OBJECTIVE Recent data suggested that sex hormone–binding globulin (SHBG) levels decrease when fat accumulates in the liver and that circulating SHBG may be causally involved in the pathogenesis of type 2 diabetes in humans. In the present study, we investigated mechanisms by which high SHBG may prevent development to diabetes. RESEARCH DESIGN AND METHODS Before and during a 9-month lifestyle intervention, total body and visceral fat were precisely measured by magnetic resonance (MR) tomography and liver fat was measured by 1H-MR spectroscopy in 225 subjects. Insulin sensitivity was estimated from a 75-g oral glucose tolerance test (ISOGTT) and measured by a euglycemic hyperinsulinemic clamp (ISclamp, n = 172). Insulin secretion was measured during the OGTT and an ivGTT (n = 172). RESULTS SHBG levels correlated positively with insulin sensitivity (ISOGTT, P = 0.037; ISclamp, P = 0.057), independently of age, sex, and total body fat. In a multivariate model, these relationships were also significant after additional adjustment for levels of the adipokine adiponectin and the hepatokine fetuin-A (ISOGTT, P = 0.0096; ISclamp, P = 0.029). Adjustment of circulating SHBG for liver fat abolished the relationships of SHBG with insulin sensitivity. In contrast, circulating SHBG correlated negatively with fasting glycemia, before (r = −0.17, P = 0.009) and after (r = −0.14, P = 0.04) adjustment for liver fat. No correlation of circulating SHBG with adjusted insulin secretion was observed (OGTT, P = 0.16; ivGTT, P = 0.35). The SNP rs1799941 in SHBG was associated with circulating SHBG (P ≤ 0.025) but not with metabolic characteristics (all P &amp;gt; 0.18). CONCLUSIONS Possible mechanisms by which high circulating SHBG prevents the development of type 2 diabetes involve regulation of fasting glycemia but not alteration of insulin secretory function.
Inhibition of microsomal prostaglandin E2synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense
2010-09-14

BACKGROUND AND PURPOSE Frankincense, the gum resin derived from Boswellia species, showed anti‐inflammatory efficacy in animal models and in pilot clinical studies. Boswellic acids (BAs) are assumed to be responsible for these effects but their anti‐inflammatory efficacy in vivo and their molecular modes of action are incompletely understood. EXPERIMENTAL APPROACH A protein fishing approach using immobilized BA and surface plasmon resonance (SPR) spectroscopy were used to reveal microsomal prostaglandin E 2 synthase‐1 (mPGES1) as a BA‐interacting protein. Cell‐free and cell‐based assays were applied to confirm the functional interference of BAs with mPGES1. Carrageenan‐induced mouse paw oedema and rat pleurisy models were utilized to demonstrate the efficacy of defined BAs in vivo . KEY RESULTS Human mPGES1 from A549 cells or in vitro ‐translated human enzyme selectively bound to BA affinity matrices and SPR spectroscopy confirmed these interactions. BAs reversibly suppressed the transformation of prostaglandin (PG)H 2 to PGE 2 mediated by mPGES1 (IC 50 = 3–10 μM). Also, in intact A549 cells, BAs selectively inhibited PGE 2 generation and, in human whole blood, β‐BA reduced lipopolysaccharide‐induced PGE 2 biosynthesis without affecting formation of the COX‐derived metabolites 6‐keto PGF 1α and thromboxane B 2 . Intraperitoneal or oral administration of β‐BA (1 mg·kg −1 ) suppressed rat pleurisy, accompanied by impaired levels of PGE 2 and β‐BA (1 mg·kg −1 , given i.p.) also reduced mouse paw oedema, both induced by carrageenan. CONCLUSIONS AND IMPLICATIONS Suppression of PGE 2 formation by BAs via interference with mPGES1 contribute to the anti‐inflammatory effectiveness of BAs and of frankincense, and may constitute a biochemical basis for their anti‐inflammatory properties.
Revisiting the Westerlund 2 field with the HESS telescope array
2010-09-14

Aims. Previous observations with the HESS telescope array revealed the existence of extended very-high-energy (VHE; E&gt;100 GeV) γ-ray emission, HESS J1023-575, coincident with the young stellar cluster Westerlund 2. At the time of discovery, the origin of the observed emission was not unambiguously identified, and follow-up observations have been performed to further investigate the nature of this γ-ray source. Methods. The Carina region towards the open cluster Westerlund 2 has been re-observed, increasing the total exposure to 45.9 h. The combined dataset includes 33 h of new data and now permits a search for energy-dependent morphology and detailed spectroscopy. Results. A new, hard spectrum VHE γ-ray source, HESS J1026-582, was discovered with a statistical significance of 7σ. It is positionally coincident with the Fermi LAT pulsar PSR J1028-5819. The positional coincidence and radio/γ-ray characteristics of the LAT pulsar favors a scenario where the TeV emission originates from a pulsar wind nebula. The nature of HESS J1023-575 is discussed in light of the deep HESS observations and recent multi-wavelength discoveries, including the Fermi LAT pulsar PSR J1022-5746 and giant molecular clouds in the region. Despite the improved VHE dataset, a clear identification of the object responsible for the VHE emission from HESS J1023-575 is not yet possible, and contribution from the nearby high-energy pulsar and/or the open cluster remains a possibility. © ESO 2010.
Astroglial structures in the zebrafish brain
2010-09-14

Abstract Parasagittal cryostat section through the dorsal zebrafish telencephalon stained with antibodies binding to glial fibrillary acidic protein (GFAP; red) and glutamine synthetase (GS; green). Long radial glial fibers were positive for both proteins with GFAP present in the main process and branches (yellow), and GS additionally in finer branches (green areas). Cell nuclei were stained with TOPRO (blue). Note that glial cell bodies are lining the ventricular surface of the everted telencephalon. The Journal of Comparative Neurology , Volume 518, Number 21, 4277–4287.
International Perspectives on Education and Society
2010-09-14

Citation (2010), "International Perspectives on Education and Society", Karin Amos, S. (Ed.) International Educational Governance (International Perspectives on Education and Society, Vol. 12), Emerald Group Publishing Limited, Bingley, p. iii. https://doi.org/10.1108/S1479-3679(2010)0000012020 Publisher: Emerald Group Publishing Limited Copyright © 2010, Emerald Group Publishing Limited Book Chapters International Perspectives on Education and Society International Perspectives on Education and Society Copyright page List of Contributors Preface International educational governance models and national policy convergence Cultural political economy and the international governance of education: A theoretical framework Regime theory and educational governance: The emergence of an international education regime The morphodynamics of modern education systems: On the relation between governance and governmentality as analytical tool in explaining current transformations Governmentality revisited: Bourdieu meets Foucault Marketing hope: Private institutions preparing students for the university entrance examination in Turkey Semantic shifts only? The ascension of the manager in the German education system Educational monitoring and reporting as governance instruments for evidence-based education policy Toward a postbureaucratic regulation regime of schools? Some questions and evidence from the European Reguleduc research Evaluation of higher education in Brazil: Rationale and goals Global Governance in Social Work About the authors Author Index Subject Index
Association between reward‐related activation in the ventral striatum and trait reward sensitivity is moderated by dopamine transporter genotype
2010-09-15

Abstract The impact of individual differences on human reward processing has been a focus of research in recent years, particularly, as they are associated with a variety of neuropsychiatric diseases including addiction and attention‐deficit/hyperactivity disorder. Studies exploring the neural basis of individual differences in reward sensitivity have consistently implicated the ventral striatum (VS) as a core component of the human reward system. However, the mechanisms of dopaminergic neurotransmission underlying ventral striatal activation as well as trait reward sensitivity remain speculative. We addressed this issue by investigating the triadic interplay between VS reactivity during reward anticipation using functional magnetic resonance imaging, trait reward sensitivity, and dopamine (DA) transporter genotype (40‐bp 3′VNTR of DAT, SLC6A3 ) affecting synaptic DA neurotransmission. Our results show that DAT variation moderates the association between VS‐reactivity and trait reward sensitivity. Specifically, homozygote carriers of the DAT 10‐repeat allele exhibit a strong positive correlation between reward sensitivity and reward‐related VS activity whereas this relationship is absent in the DAT 9‐repeat allele carriers. We discuss the possibility that this moderation of VS‐trait relation might arise from DAT ‐dependent differences in DA availability affecting synaptic plasticity within the VS. Generally, studying the impact of dopaminergic gene variations on the relation between reward‐related brain activity and trait reward sensitivity might facilitate the investigation of complex mechanisms underlying disorders linked to dysregulation of DA neurotransmission. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Biological origins of normal-chain hydrocarbons: a pathway model based on cuticular wax analyses of maize silks
2010-09-15

Long-chain normal hydrocarbons (e.g. alkanes, alkenes and dienes) are rare biological molecules and their biosynthetic origins are obscure. Detailed analyses of the surface lipids that accumulate on maize silks have revealed that these hydrocarbons constitute a large portion (>90%) of the cuticular waxes that coat this organ, which contrasts with the situation on maize seedling leaves, where the cuticular waxes are primary alcohols and aldehydes. The normal hydrocarbons that occur on silks are part of a homologous series of alkanes, alkenes and dienes of odd-number carbon atoms, ranging between 19 and 33 in number. The alkenes and dienes consist of a homologous series, each of which has double bonds situated at defined positions of the alkyl chains: alkenes have double bonds situated at the sixth, ninth or 12th positions, and dienes have double bonds situated at the sixth and ninth, or ninth and twelfth positions. Finding a homologous series of unsaturated aldehydes and fatty acids suggests that these alkenes and dienes are biosynthesized by a series of parallel pathways of fatty-acid elongation and desaturation reactions, which are followed by sequential reduction and decarbonylation. In addition, the silk cuticular waxes contain metabolically related unsaturated long-chain methylketones, which probably arise via a decarboxylation mechanism. Finally, metabolite profiling analyses of the cuticular waxes of two maize inbred lines (B73 and Mo17), and their genetic hybrids, have provided insights into the genetic control network of these biosynthetic pathways, and that the genetic regulation of these pathways display best-parent heterotic effects.
The Impact of Thyroid Disease on the Regulation, Expression, and Function of ABCB1 (MDR1/P Glycoprotein) and Consequences for the Disposition of Digoxin
2010-09-15

The impact of thyroid dysfunction on the regulation, expression, and function of ABCB1 remains unclear. We therefore investigated ABCB1 mRNA expression and function in patients with thyroid dysfunction and studied the disposition of the ABCB1 substrate digoxin before and after treatment for thyroid disease. In patients with hypothyroidism, normalization of thyroid function was associated with a 1.8-fold increase in mRNA expression and a 26% increase in rhodamine efflux from CD56(+) cells. In hypothyroidism, digoxin clearance was significantly decreased, whereas bioavailability, volume of distribution, half-life time, and protein binding were unaltered. In hyperthyroidism, ABCB1 mRNA expression, rhodamine efflux, and disposition of digoxin were not significantly affected other than in relation to renal clearance. Experiments using the LS174T cell line indicated that the gene is a direct target of thyroid hormone receptors. In conclusion, thyroid abnormalities can exert significant effects on the expression of P-glycoprotein, thereby altering the disposition and action of drugs that are substrates of P-glycoprotein.
A late form of neurosyphilis manifesting with psychotic symptoms in old age and good response to ceftriaxone therapy
2010-09-15

Neurosyphilis can present with psychiatric symptoms. The late form can occur in old age with psychosis, paranoid delusions, affective disorders or cognitive impairment. Here we present a case of neurosyphilis in an elderly woman who, over six months, progressively manifested personality changes and paranoid delusions which were initially suspected as Alzheimer's disease. Psychotic symptoms showed a good response to antibiotic treatment. We conclude that neurosyphilis is a relevant differential diagnosis in patients developing severe psychiatric symptoms in old age. As a causal antibiotic treatment is possible this infectious disease should be considered seriously in gerontopsychiatric patients.
On the effects of fair trade on the welfare of the poor
2010-09-15

Abstract Despite the rising importance of fair trade (FT), a relatively small amount of academic research has been done in this area so far. Advocates of FT claim that it will ultimately improve the living conditions of the poor. Opponents hold that it will worsen their situation. More often than not, public discussion is affected by dogmatic views, prejudices and emotional charges. This paper aims to contribute to an objective discussion of the topic. We present a matching model to analyse the welfare effects of FT in an agricultural market. Our results show that producers obtaining FT certification are better off. All others will lose if incentives for importers to enter the market decline. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Synthesis of Benzofuran, Benzothiophene, and Benzothiazole‐Based Thioamides and their Evaluation as KATP Channel Openers
2010-09-15

Abstract Several series of benzofurans, benzothiophenes, and benzothiazoles, all featuring the thioamide group, were synthesized and tested as novel K ATP channel openers in artificial cell systems: CHO cells transfected with SUR1/Kir6.2, and HEK 293 cells transfected with SUR2B/Kir6.1; these served as model systems for insulin‐secreting pancreatic β cells and smooth muscle cells, respectively. All compounds were investigated with respect to their binding affinity for the SUR2B‐type K ATP channels using [ 3 H]P1075 as radioligand. Selected compounds were also tested as agonists in intact cells using DiBAC 4 (3) and DyeB (R7260) as membrane potential dyes. Remarkable affinity for SUR2B/Kir6.1 channels in the single‐digit micromolar range was observed. In addition, benzothiazole‐derived thioamides with sterically demanding, lipophilic substituents showed &gt;100‐fold selectivity in favor of SUR2B/Kir6.1. A one‐carbon spacer between the heterocyclic skeleton and the thioamide moiety was observed to be crucial for affinity and selectivity. Two of the most potent and selective compounds were studied by crystal structure analyses.
ABA promotes quiescence of the quiescent centre and suppresses stem cell differentiation in the Arabidopsis primary root meristem
2010-09-16

It is well known that abscisic acid (ABA) can halt meristems for long periods without loss of meristem function, and can also promote root growth at low concentrations, but the mechanisms underlying such regulation are largely unknown. Here we show that ABA promotes stem cell maintenance in Arabidopsis root meristems by both promoting the quiescence of the quiescent centre (QC) and suppressing the differentiation of stem cells and their daughters. We demonstrate that these two mechanisms of regulation by ABA involve distinct pathways, and identify components in each pathway. Our findings demonstrate a cellular mechanism for a positive role for ABA in promoting root meristem maintenance and root growth in Arabidopsis.
Saxagliptin is non-inferior to glipizide in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: a 52-week randomised controlled trial
2010-09-16

Saxagliptin plus metformin was well tolerated, provided a sustained HbA(1c) reduction over 52 weeks, and was non-inferior to glipizide plus metformin, with reduced body weight and a significantly lower risk of hypoglycaemia.