julilili42/papers huggingface dataset:
Combined Optogenetic and Freeze-fracture Replica Immunolabeling to Examine Input-specific Arrangement of Glutamate Receptors in the Mouse Amygdala
2016-04-15

Freeze-fracture electron microscopy has been a major technique in ultrastructural research for over 40 years. However, the lack of effective means to study the molecular composition of membranes produced a significant decline in its use. Recently, there has been a major revival in freeze-fracture electron microscopy thanks to the development of effective ways to reveal integral membrane proteins by immunogold labeling. One of these methods is known as detergent-solubilized Freeze-fracture Replica Immunolabeling (FRIL). The combination of the FRIL technique with optogenetics allows a correlated analysis of the structural and functional properties of central synapses. Using this approach it is possible to identify and characterize both pre- and postsynaptic neurons by their respective expression of a tagged channelrhodopsin and specific molecular markers. The distinctive appearance of the postsynaptic membrane specialization of glutamatergic synapses further allows, upon labeling of ionotropic glutamate receptors, to quantify and analyze the intrasynaptic distribution of these receptors. Here, we give a step-by-step description of the procedures required to prepare paired replicas and how to immunolabel them. We will also discuss the caveats and limitations of the FRIL technique, in particular those associated with potential sampling biases. The high reproducibility and versatility of the FRIL technique, when combined with optogenetics, offers a very powerful approach for the characterization of different aspects of synaptic transmission at identified neuronal microcircuits in the brain. Here, we provide an example how this approach was used to gain insights into structure-function relationships of excitatory synapses at neurons of the intercalated cell masses of the mouse amygdala. In particular, we have investigated the expression of ionotropic glutamate receptors at identified inputs originated from the thalamic posterior intralaminar and medial geniculate nuclei. These synapses were shown to relay sensory information relevant for fear learning and to undergo plastic changes upon fear conditioning.
The Logic of Law Making in Islam: Women and Prayer in the Legal TraditionBehnam Sadeghi Cambridge University Press, Cambridge, 2013, Cambridge Studies in Islamic Civilization, xxi + 215 pp (hardback £64.99) ISBN: 978-1-107-00909-7; (paperback £19.99) ISBN: 978-1-107-52978-6
2016-04-15

The Logic of Law Making in Islam: Women and Prayer in the Legal TraditionBehnam Sadeghi Cambridge University Press, Cambridge, 2013, Cambridge Studies in Islamic Civilization, xxi + 215 pp (hardback £64.99) ISBN: 978-1-107-00909-7; (paperback £19.99) ISBN: 978-1-107-52978-6 - Volume 18 Issue 2
SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large multi-centre study
2016-04-17

Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene have been reported to cause a relatively pure, slowly progressive cerebellar recessive ataxia mostly identified in Quebec, Canada. Combining next-generation sequencing techniques and deep-phenotyping (clinics, magnetic resonance imaging, positron emission tomography, muscle histology), we here established the frequency, phenotypic spectrum and genetic spectrum of SYNE1 in a screening of 434 non-Canadian index patients from seven centres across Europe. Patients were screened by whole-exome sequencing or targeted panel sequencing, yielding 23 unrelated families with recessive truncating SYNE1 mutations (23/434 = 5.3%). In these families, 35 different mutations were identified, 34 of them not previously linked to human disease. While only 5/26 patients (19%) showed the classical SYNE1 phenotype of mildly progressive pure cerebellar ataxia, 21/26 (81%) exhibited additional complicating features, including motor neuron features in 15/26 (58%). In three patients, respiratory dysfunction was part of an early-onset multisystemic neuromuscular phenotype with mental retardation, leading to premature death at age 36 years in one of them. Positron emission tomography imaging confirmed hypometabolism in extra-cerebellar regions such as the brainstem. Muscle biopsy reliably showed severely reduced or absent SYNE1 staining, indicating its potential use as a non-genetic indicator for underlying SYNE1 mutations. Our findings, which present the largest systematic series of SYNE1 patients and mutations outside Canada, revise the view that SYNE1 ataxia causes mainly a relatively pure cerebellar recessive ataxia and that it is largely limited to Quebec. Instead, complex phenotypes with a wide range of extra-cerebellar neurological and non-neurological dysfunctions are frequent, including in particular motor neuron and brainstem dysfunction. The disease course in this multisystemic neurodegenerative disease can be fatal, including premature death due to respiratory dysfunction. With a relative frequency of ∼5%, SYNE1 is one of the more common recessive ataxias worldwide.
USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment
2016-04-18

Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. Most endometrial cancer cases are diagnosed at an early stage and have good prognosis. Unfortunately a subset of patients with early stage and low grade disease experience recurrence for reasons that remain unclear. Recurrence is often accompanied by chemoresistance and high mortality.Deubiquitinating enzymes (DUBs) are key components of the ubiquitin-dependent protein degradation pathway and act as master regulators in a number of metabolic processes including cell growth, differentiation, and apoptosis. DUBs have been shown to be upregulated in a number of human cancers and their aberrant activity has been linked to cancer progression, initiation and onset of chemoresistance. Thus, selective inhibition of DUBs has been proposed as a targeted therapy for cancer treatment.This study suggests the DUB USP14 as a promising biomarker for stratifying endometrial cancer patients at diagnosis based on their risk of recurrence. Further USP14 is expressed along with the marker of proliferation Ki67 in endometrial cancer cells in situ. Lastly, pharmacological targeting of USP14 with the FDA approved small-molecule inhibitor VLX1570, decreases cell viability in chemotherapy resistant endometrial cancer cells with a mechanism consistent with cell cycle arrest and caspase-3 mediated apoptosis.
First Record of Anisoptera (Insecta: Odonata) from mid-Cretaceous Burmese Amber
2016-04-18

The fossil dragonfly Burmalindenia imperfecta gen. et sp. nov. is described from mid-Cretaceous Burmese amber as the first record of the odonate suborder Anisoptera for this locality and one of the few records from amber in general. The inclusion comprises two fragments of the two hind wings of a dragonfly. The fossil can be attributed to a new genus and species of the family Gomphidae, presumably in the subfamily Lindeniinae, and features a strange teratological phenomenon in its wing venation.
Autobiographical Memory Performance in Alzheimer’s Disease Depends on Retrieval Frequency
2016-04-18

Alzheimer’s disease (AD) is characterized by memory disturbances primarily caused by pathogenic mechanisms affecting medial temporal lobe structures. As proposed by current theories of memory formation, this decrease is mediated by the age of the acquired knowledge. However, they cannot fully explain specific patterns of retrograde amnesia in AD. In the current study we examined an alternative approach and investigated whether the extent and severity of retrograde amnesia in AD is mediated by the frequency of memory retrieval or whether it depends on the mere age of knowledge. We compared recall of autobiographical incidents from three life periods in patients with amnestic mild cognitive impairment (aMCI), patients with early dementia of Alzheimer type (eDAT), and healthy control (HC) individuals using the Autobiographical Memory Interview. Retrieval frequency was operationalized by a paired comparison analysis. In contrast to HC individuals, recall of autobiographical incidents was impaired in patients with aMCI and eDAT following Ribot’s gradient, with a reduced memory loss for remote compared to more recent life events. However, there was a strong effect of retrieval frequency on memory performance with frequently retrieved incidents memorized in more detail than less frequently retrieved episodes. Remote memories were recalled more often than recent ones. These findings suggest that more frequently retrieved autobiographical memories generally become more independent of the hippocampal complex and might thus be better protected against early hippocampal damage related to AD. Hence, the extent of retrograde amnesia in AD appears mainly mediated by the frequency of memory retrieval, which could plausibly explain why cognitive activity can effectively delay the onset of memory decline in AD.
Allelochemicals of the phenoxazinone class act at physiologically relevant concentrations
2016-04-18

Plants compete with their neighbors via the release of chemical compounds into the rhizosphere. These phytotoxins originate from a series of secondary metabolites and can be processed further by soil-living microorganisms before exerting their activity on the target plant. To determine the molecular mode of action and the physiological relevance of potential phytotoxins, it is important to simulate true-to-life conditions in laboratory experiments, for example by applying physiologically relevant concentrations. Here, we report on an improved experimental setting to study the function of allelochemicals of the benzoxazolinone class. By adjusting the solvent and the application of the chemicals, we reduced by more than 2fold the concentration that is necessary to induce growth defects in the model plant Arabidopsis thaliana.
HiQuant: Rapid Postquantification Analysis of Large-Scale MS-Generated Proteomics Data
2016-04-18

Recent advances in mass-spectrometry-based proteomics are now facilitating ambitious large-scale investigations of the spatial and temporal dynamics of the proteome; however, the increasing size and complexity of these data sets is overwhelming current downstream computational methods, specifically those that support the postquantification analysis pipeline. Here we present HiQuant, a novel application that enables the design and execution of a postquantification workflow, including common data-processing steps, such as assay normalization and grouping, and experimental replicate quality control and statistical analysis. HiQuant also enables the interpretation of results generated from large-scale data sets by supporting interactive heatmap analysis and also the direct export to Cytoscape and Gephi, two leading network analysis platforms. HiQuant may be run via a user-friendly graphical interface and also supports complete one-touch automation via a command-line mode. We evaluate HiQuant's performance by analyzing a large-scale, complex interactome mapping data set and demonstrate a 200-fold improvement in the execution time over current methods. We also demonstrate HiQuant's general utility by analyzing proteome-wide quantification data generated from both a large-scale public tyrosine kinase siRNA knock-down study and an in-house investigation into the temporal dynamics of the KSR1 and KSR2 interactomes. Download HiQuant, sample data sets, and supporting documentation at http://hiquant.primesdb.eu .
Quality Requirements for the early Fetal Ultrasound Assessment at 11–13+6 Weeks of Gestation (DEGUM Levels II and III)
2016-04-19

The early fetal ultrasound assessment at 11 - 13(+6) weeks of gestation remains the cornerstone of care despite the progress in diagnosing fetal chromosomal defects using cell-free fetal DNA (cffDNA) from the maternal circulation. The measurement of nuchal translucency (NT) allows the risk calculation for the fetal trisomies 21, 18 and 13 but also gives information on those fetal chromosomal defects which are at present unable to be detected using cffDNA. Nuchal translucency is the only auditable parameter at 11 - 13(+6) weeks and gives thus information on the quality of the first trimester anomaly scan. In addition it gives indirect information on the risks for fetal defects and for cardiac anomalies. Also the chances for a healthy live baby can be estimated. As experience with first trimester anomaly scanning increases, and the resolution of the ultrasound equipment has increased substantially, more and more details of the fetal anatomy become accessible at the first trimester scan. Therefore fetal anatomical defects and complex anomalies have become amenable to examination in the first trimester. This guideline describes compulsory and optional parameters for investigation at the first trimester scan and outlines a structured method of examining a first trimester fetus at 11 - 13(+6) weeks of gestation.
The Atypical Inhibitor of NF-κB, IκBζ, Controls Macrophage Interleukin-10 Expression
2016-04-19

Macrophages constitute a first line of pathogen defense by triggering a number of inflammatory responses and the secretion of various pro-inflammatory cytokines. Recently, we and others found that IÎoBÎ¶, an atypical IÎoB family member and transcriptional coactivator of selected NF-ÎoB target genes, is essential for macrophage expression of a subset of pro-inflammatory cytokines, such as IL-6, IL-12, and CCL2. Despite defective pro-inflammatory cytokine expression, however, IÎoBÎ¶-deficient mice develop symptoms of chronic inflammation. To elucidate this discrepancy, we analyzed a regulatory role of IÎoBÎ¶ for the expression of anti-inflammatory cytokines and identified IÎoBÎ¶ as an essential activator of IL-10 expression. LPS-challenged peritoneal and bone marrow-derived macrophages from IÎoBÎ¶-deficient mice revealed strongly decreased transcription and secretion of IL-10 compared with wild-type mice. Moreover, ectopic expression of IÎoBÎ¶ was sufficient to stimulate Il10 transcription. On the molecular level, IÎoBÎ¶ directly activated the Il10 promoter at a proximal ÎoB site and was required for the transcription-enhancing trimethylation of histone 3 at lysine 4. Together, our findings show for the first time the IÎoBÎ¶-dependent expression of an anti-inflammatory cytokine that is crucial in controlling immune responses.
Tyrosine 601 of Bacillus subtilis DnaK Undergoes Phosphorylation and Is Crucial for Chaperone Activity and Heat Shock Survival‡
2016-04-19

In order to screen for cellular substrates of the Bacillus subtilis BY-kinase PtkA, and its cognate phosphotyrosine-protein phosphatase PtpZ, we performed a triple Stable Isotope Labeling by Amino acids in Cell culture-based quantitative phosphoproteome analysis. Detected tyrosine phosphorylation sites for which the phosphorylation level decreased in the ΔptkA strain and increased in the ΔptpZ strain, compared to the wild type (WT), were considered as potential substrates of PtkA/PtpZ. One of those sites was the residue tyrosine 601 of the molecular chaperone DnaK. We confirmed that DnaK is a substrate of PtkA and PtpZ by in vitro phosphorylation and dephosphorylation assays. In vitro, DnaK Y601F mutant exhibited impaired interaction with its co-chaperones DnaJ and GrpE, along with diminished capacity to hydrolyze ATP and assist the re-folding of denatured proteins. In vivo, loss of DnaK phosphorylation in the mutant strain dnaK Y601F, or in the strain overexpressing the phosphatase PtpZ, led to diminished survival upon heat shock, consistent with the in vitro results. The decreased survival of the mutant dnaK Y601F at an elevated temperature could be rescued by complementing with the WT dnaK allele expressed ectopically. We concluded that the residue tyrosine 601 of DnaK can be phosphorylated and dephosphorylated by PtkA and PtpZ, respectively. Furthermore, Y601 is important for DnaK chaperone activity and heat shock survival of B. subtilis.
The genetic variant I148 M in PNPLA3 is associated with increased hepatic retinyl-palmitate storage in humans
2016-04-19

Context: Previous studies revealed that the common sequence variant I148 M in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with liver fat content and liver diseases, but not with insulin resistance. Recent data suggest that the PNPLA3 I148 M variant has reduced retinyl-palmitate lipase activity in hepatic stellate cells.
Recent developments in the tidal deformability of spinning compact objects
2016-04-19

We review recent work on the theory of tidal deformability and the tidal Love numbers of a slowly spinning compact object within general relativity. Angular momentum introduces couplings between distortions of different parity and new classes of spin-induced, tidal Love numbers emerge. Due to spin-tidal effects, a rotating object immersed in a quadrupolar, electric tidal field can acquire some induced mass, spin, quadrupole, octupole and hexadecapole moments to second-order in the spin. The tidal Love numbers depend strongly on the object’s internal structure. All tidal Love numbers of a Kerr black hole (BH) were proved to be exactly zero to first-order in the spin and also to second-order in the spin, at least in the axisymmetric case. For a binary system close to the merger, various components of the tidal field become relevant. Preliminary results suggest that spin-tidal couplings can introduce important corrections to the gravitational waveforms of spinning neutron star (NS) binaries approaching the merger.
Differential trends in households’ connection to the Internet: An actor-centered explanation:
2016-04-19

In this article, an actor-centered model of households’ decision to obtain an Internet connection is set up to explain the diffusion of Internet technology. First, we derive a mechanism based on the demand and supply of online information, services, and goods which drives this diffusion. Afterwards, we link this mechanism to social inequalities with regard to digital technologies and deduce hypotheses regarding changes in the relevance of different socio-structural factors for adopting an Internet connection over the diffusion process. In our analyses, we address the following research questions: Which socio-structural differentiations persist over the diffusion process and why? How much of the inequality in the diffusion of Internet connections by socio-economic status can be explained by differences in information technology competencies and resource restrictions? We test our model with a discrete time transition rate analysis and Socio-Economic Panel data. Overall, our model rationalizes about 75% of t...
Differential apelin mRNA expression in placenta of women with gestational diabetes (GDM)
2016-04-19

The percentage of pregnancies accompanied by gestational diabetes (GDM) is increasing globally. Also, GDM and the associated disturbances in maternal lipid metabolism are shown to have negative impacts on maternal and fetal long term health. In normoglycemic women (NGT), the pancreas can compensate for the reduction in insulin sensitivity being present in the 3rd trimester of pregnancy. However in GDM, the compensatory beta cell response is absent. It is proposed that adipokines, also released from the placenta might lead to reduced compensatory effects of the beta cells.
KATP channel-dependent and -independent protection against glucolipotoxicity-induced damage of mouse beta-cells
2016-04-19

Background: Obesity leads to oxidative stress and glucolipotoxicity (Gltx) which affect the metabolic integrity of beta-cells. The present work aimed to clarify whether genetic and pharmacological deletion of functional KATP channels prevents Gltx-induced metabolic damage as shown before for oxidative stress.
Differential trends in households’ connection to the Internet: An actor-centered explanation
2016-04-19

In this article, an actor-centered model of households’ decision to obtain an Internet connection is set up to explain the diffusion of Internet technology. First, we derive a mechanism based on the demand and supply of online information, services, and goods which drives this diffusion. Afterwards, we link this mechanism to social inequalities with regard to digital technologies and deduce hypotheses regarding changes in the relevance of different socio-structural factors for adopting an Internet connection over the diffusion process. In our analyses, we address the following research questions: Which socio-structural differentiations persist over the diffusion process and why? How much of the inequality in the diffusion of Internet connections by socio-economic status can be explained by differences in information technology competencies and resource restrictions? We test our model with a discrete time transition rate analysis and Socio-Economic Panel data. Overall, our model rationalizes about 75% of the gross inequality by socio-economic status between households’ choices to connect to the Internet. Regarding the persistence of social inequalities in adopting digital technologies, our study highlights the importance of structural opportunities to develop strategic information technology competencies during socialization. With respect to related indicators, our analyses show an about 13-fold increase in the influence of birth cohort differences on the adoption of Internet connections over the diffusion process. As a consequence, a central implication of our study is that we expect birth cohort differences in the diffusion of digital technologies not only to persist, but to increase.
Slowly rotating neutron stars in scalar-tensor theories with a massive scalar field
2016-04-20

In the scalar-tensor theories with a massive scalar field the coupling\\nconstants, and the coupling functions in general, which are observationally\\nallowed, can differ significantly from those in the massless case. This fact\\nnaturally implies that the scalar-tensor neutron stars with a massive scalar\\nfield can have rather different structure and properties in comparison with\\ntheir counterparts in the massless case and in general relativity. In the\\npresent paper we study slowly rotating neutron stars in scalar-tensor theories\\nwith a massive gravitational scalar. Two examples of scalar-tensor theories are\\nexamined - the first example is the massive Brans-Dicke theory and the second\\none is a massive scalar-tensor theory indistinguishable from general relativity\\nin the weak field limit. In the later case we study the effect of the scalar\\nfield mass on the spontaneous scalarization of neutron stars. Our numerical\\nresults show that the inclusion of a mass term for the scalar field indeed\\nchanges the picture drastically compared to the massless case. It turns out\\nthat mass, radius and moment of inertia for neutron stars in massive\\nscalar-tensor theories can differ drastically from the pure general\\nrelativistic solutions if sufficiently large masses of the scalar field are\\nconsidered.\\n