julilili42/papers huggingface dataset:
The Lewis Acidity of the BO Triple Bond in Methyl(oxo)borane
2013-04-11

Abstract The interaction of methyl(oxo)borane, CH 3 BO, with typical Lewis bases (nitrogen based and N‐heterocyclic carbenes) was investigated using density functional theory (B97‐D, TPSS‐D3), double hybrid density functionals (PWPB95‐D3, B2PLYP‐D3) in conjunction with empirical dispersion corrections, and coupled cluster theory involving singles, doubles, and a perturbative estimate of triple excitations [CCSD(T)]. A polarized quadruple‐zeta basis set was used throughout. The interaction energies computed with the double‐hybrid methods agree very well with CCSD(T). Compared to typical boron Lewis acids, the interaction energies are much smaller for methyl(oxo)borane, indicating that the BO triple bond results in significantly reduced Lewis acidity. An analysis of the mechanical bond strengths in CH 3 BO and its complexes indicates that the relaxed BO force constants (compliance constants) and the stretching vibrations decrease with increasing strengths of the dative interactions.
PRESCRIBING AND RESEARCH IN MEDICINES MANAGEMENT (UK & IRELAND)
2013-04-11

To evaluate the daily drug cost of critically ill patients and investigate this in terms of severity of illness and mortality.This is via designing a patient specific and reproducible method that accommodates for the diversity of critically ill patients.
Triggered fragmentation in gravitationally unstable discs:\\n forming fragments at small radii
2013-04-11

\\n We carry out three dimensional radiation hydrodynamical simulations of gravitationally\\n unstable discs using to explore the movement of mass in a disc following its\\n fragmentation. Compared to a more quiescent state before it fragments, the radial velocity\\n of the gas increases by up to a factor of ≈ 2 – 3 after fragmentation. While the mass\\n movement occurs both inwards and outwards, the inwards motion can cause the inner spirals\\n to be suciently dense that they may become unstable and potentially fragment.\\n Consequently, the dynamical behaviour of fragmented discs may cause subsequent\\n fragmentation at smaller radii after an initial fragment has formed in\\n the outer disc.\\n
Accurate detection of differential RNA processing
2013-04-12

Deep transcriptome sequencing (RNA-Seq) has become a vital tool for studying the state of cells in the context of varying environments, genotypes and other factors. RNA-Seq profiling data enable identification of novel isoforms, quantification of known isoforms and detection of changes in transcriptional or RNA-processing activity. Existing approaches to detect differential isoform abundance between samples either require a complete isoform annotation or fall short in providing statistically robust and calibrated significance estimates. Here, we propose a suite of statistical tests to address these open needs: a parametric test that uses known isoform annotations to detect changes in relative isoform abundance and a non-parametric test that detects differential read coverages and can be applied when isoform annotations are not available. Both methods account for the discrete nature of read counts and the inherent biological variability. We demonstrate that these tests compare favorably to previous methods, both in terms of accuracy and statistical calibrations. We use these techniques to analyze RNA-Seq libraries from Arabidopsis thaliana and Drosophila melanogaster. The identified differential RNA processing events were consistent with RT-qPCR measurements and previous studies. The proposed toolkit is available from http://bioweb.me/rdiff and enables in-depth analyses of transcriptomes, with or without available isoform annotation.
Somatic hypermutation analysis in follicular lymphoma provides evidence suggesting bidirectional cell migration between lymph node and bone marrow during disease progression and relapse
2013-04-12

In follicular lymphoma, somatic hypermutation of the immunoglobulin heavy chain genes facilitates the identification of different lymphoma cell clones, and the construction of genealogical trees. To investigate the dissemination of lymphoma cells, and the role of bone marrow in disease progression, we simultaneously analyzed the somatic hypermutation patterns of lymph node and bone marrow specimens taken from three patients at onset and relapse of their disease. Immunoglobulin heavy chain genes were amplified by polymerase chain reaction, cloned and sequenced. Mutational pedigrees were constructed in a hierarchical order. When direct transition of one mutation pattern into that of a successor clones was not feasible, hypothetical predecessor clones were created, and a probability measurement calculation was introduced. Eighty-five sequenced clones were generated. The average mutation rates were 13.45% for the lymph node specimens, and 9.78% for the bone marrow ones. Forty-two hypothetical predecessor clones were introduced into inter-compartment pedigrees. The genealogical trees showed that early lymphoma clones with a low mutational load quickly migrate from lymph nodes into the bone marrow. Bi-directional lymphoma cell migration was detectable between the two compartments. In one case of follicular lymphoma, a clone identical to the initial lymph node clone was detected 2 years later in the bone marrow. The newly introduced algorithm allows the evaluation of both time and direction of follicular lymphoma cell migration. We found evidence that follicular lymphoma originates in the lymph node, and infiltrates the bone marrow early in the course of the disease. Moreover, inter-compartment migration between lymph nodes and bone marrow occurs in both directions.
The PDZ-interaction of the intestinal anion exchanger downregulated in adenoma (DRA; SLC26A3) facilitates its movement into Rab11a-positive recycling endosomes
2013-04-12

Electroneutral NaCl absorption in the ileum and colon is mediated by downregulated in adenoma (DRA) (Cl - /HCO 3 - exchanger; SLC26A3) and Na + /H + exchanger 3 (NHE3, SLC9A3). Surface expression of transport proteins undergoes basal and regulated recycling by endo- and exocytosis. Expression and activity of DRA in the plasma membrane depend on intact lipid rafts, phosphatidylinositol 3-kinase (PI3-kinase), and the PDZ interaction of DRA. However, it is unknown how the PDZ interaction of DRA affects its trafficking to the cell surface. Therefore, the (re)cycling pathway of DRA was investigated in HEK cells stably expressing enhanced green fluorescent protein (EGFP)-DRA or EGFP-DRA-ETKFminus (a mutant lacking the PDZ interaction motif). Early, late, and recycling endosomes were immunoisolated by precipitating stably transfected mCherry-hemagglutinin (HA)-Rab5a, -7a, or -11a. EGFP-DRA and EGFP-DRA-ETKFminus were equally present in early endosomes. In recycling endosomes, wild-type DRA was preferentially present, whereas, in late endosomes, DRA-ETKF-minus dominated. Correspondingly, EGFP-DRA colocalized with mCherry-HA-Rab11a in recycling endosomes, whereas EGFP-DRA-ETKFminus colocalized with mCherry-HA-Rab7a in late endosomes. Functionally, this different distribution was reflected by a shorter half-life of the mutant DRA. Transient expression of dominant-negative Rab11a S25N inhibited the activity (-17%, P &lt; 0.05) and the cell surface expression of DRA (-30%, P &lt; 0.05). Transient transfection of Rab4a or its dominant-negative mutant Rab4a S22N was without effect and thus excluded participation of the rapid recycling pathway. Taken together, the PDZ interaction of DRA facilitates its movement into Rab11a-positive recycling endosomes, from where it is inserted in the plasma membrane. A scenario emerges where specific PDZ adaptor proteins are present along several compartments of the endocytosis-recycling pathway.
Plasmodium vivax malaria in Duffy-negative individuals from Ethiopia
2013-04-13

This study documents the emergence of P. vivax malaria in Duffy-negative individuals in Ethiopia. The Duffy-negative blood group does not appear to provide absolute protection against P. vivax infection in this region.
UPDtool: a tool for detection of iso- and heterodisomy in parent–child trios using SNP microarrays
2013-04-14

Abstract Summary: UPDtool is a computational tool for detection and classification of uniparental disomy (UPD) in trio SNP-microarray experiments. UPDs are rare events of chromosomal malsegregation and describe the condition of two homologous chromosomes or homologous chromosomal segments that were inherited from one parent. The occurrence of UPD can be of major clinical relevance. Though high-throughput molecular screening techniques are widely used, detection of UPDs and especially the subclassification remains complex. We developed UPDtool to detect and classify UPDs from SNP microarray data of parent–child trios. The algorithm was tested using five positive controls including both iso- and heterodisomic segmental UPDs and 30 trios from the HapMap project as negative controls. With UPDtool, we were able to correctly identify all occurrences of non-mosaic UPD within our positive controls, whereas no occurrence of UPD was found within our negative controls. In addition, the chromosomal breakage points could be determined more precisely than by microsatellite analysis. Our results were compared with both the gold standard, microsatellite analysis and SNPtrio, another program available for UPD detection. UPDtool is platform independent, light weight and flexible. Because of its simple input format, UPDtool may also be used with other high-throughput technologies (e.g. next-generation sequencing). Availability and implementation: UPDtool executables, documentation and examples can be downloaded from http://www.uni-tuebingen.de/uni/thk/de/f-genomik-software.html. Contact: christopher.schroeder@med.uni-tuebingen.de Supplementary information: Supplementary data are available at Bioinformatics online.
Interplay of pH and Binding of Multivalent Metal Ions: Charge Inversion and Reentrant Condensation in Protein Solutions
2013-04-15

Tuning of protein surface charge is a fundamental mechanism in biological systems. Protein charge is regulated in a physiological context by pH and interaction with counterions. We report on charge inversion and the related reentrant condensation in solutions of globular proteins with different multivalent metal cations. In particular, we focus on the changes in phase behavior and charge regulation due to pH effects caused by hydrolysis of metal ions. For several proteins and metal salts, charge inversion as measured by electrophoretic light scattering is found to be a universal phenomenon, the extent of which is dependent on the specific protein-salt combination. Reentrant phase diagrams show a much narrower phase-separated regime for acidic salts such as AlCl3 and FeCl3 compared to neutral salts such as YCl3 or LaCl3. The differences between acidic and neutral salts can be explained by the interplay of pH effects and binding of the multivalent counterions. The experimental findings are reproduced with good agreement by an analytical model for protein charging taking into account ion condensation, metal ion hydrolysis, and interaction with charged amino acid side chains on the protein surface. Finally, the relationship of charge inversion and reentrant condensation is discussed, suggesting that pH variation in combination with multivalent cations provides control over both attractive and repulsive interactions between proteins.
Phosphastannirane: A Phosphorus/Tin(II) Lewis Pair that Undergoes Alkyne and Alkene Addition
2013-04-15

Bermuda triangle: The first molecule containing a cyclic three-membered SnCP ring has been synthesized and characterized. This SnIIP Lewis pair reacts at room temperature with alkynes and pentene to give the five-membered cyclic addition products. In the case of pentene, this reaction is reversible at room temperature. Trip=2,4,6-iPr3C6H2. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Impaired Identification of Threat-Related Social Information in Male Delinquents With Antisocial Personality Disorder
2013-04-15

The present study aimed to investigate the identification of threat-related facial expressions in aggressive individuals with antisocial personality disorder (ASPD). Thirty-two male delinquents and matched healthy controls were presented with a series of animated morph-clips that gradually display the onset and development of angry, fearful, and happy facial expressions. ASPD subjects required significantly higher levels of emotional intensity to correctly identify the onset of an angry facial expression as compared to control participants. In contrast, recognition of fearful and happy expressions was unimpaired. These findings suggest a specific deficit in the identification of hostile facial expressions in ASPD populations.
Teaching Neuro Images : MRI guides genetics
2013-04-15

A 12-year-old German girl presented with progressive spastic-ataxic gait and impaired fine motor skills starting from early childhood. MRI revealed striking T2-signal abnormalities in the cerebral and cerebellar white matter, pyramidal tracts and dorsal columns of the spinal cord, as well as lactate elevation in magnetic resonance spectroscopy, indicating leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) (figure). Sequencing of DARS2 1 revealed compound heterozygous frame shift and premature stop mutations (established c.228-11C>G, novel c.617_663del).
Molecular Imaging of Expression of Vascular Endothelial Growth Factor a (VEGF A) in Femoral Bone Grafts Transplanted into Living Mice
2013-04-15

The biology of cells transplanted with bone grafts is incompletely understood. Focusing on the early angiogenic response postgrafting, we report a mouse femur graft model in which grafts were derived from mice transgenic for a firefly luciferase (FLuc) bioluminescence reporter gene driven by a promoter for the angiogenic signaling molecule vascular endothelial growth factor (VEGF). Upon transplantation into wild-type (wt) mice, in vivo bioluminescence imaging (BLI) permitted longitudinal visualization and measurements of VEGF promoter activity in the transplanted graft cells and demonstrated a lag period of 7 days posttransplantation prior to robust induction of the promoter. To determine cellular mediators of VEGF induction in graft bone, primary graft-derived osteoblastic cells (GDOsts) were characterized. In vitro BLI on GDOsts showed hypoxia-induced VEGF expression and that this induction depended on PI3K signaling and, to a lesser degree, on the MEK pathway. This transcriptional regulation correlated with VEGF protein production and was validated in GDOsts seeded on demineralized bone matrix (DBM), a bone graft substitute material. Together, combined imaging of VEGF expression in living animals and in live cells provided clues about the regulation of VEGF in cells post-bone grafting. These data are particularly significant toward the development of future smart bone graft substitutes.
Biopolymers from Animals
2013-04-15

This chapter contains sections titled: Introduction Chitin and Hyaluronic Acid in the Living World Milestones in Chitin History From Trehalose to Chitin Chitin Synthase Regulation of Chitin Synthesis in Fungi Organization of Chitin in the Fungal Cell Wall Organization of Chitin in the Arthropod Cuticle Chitin-Organizing Factors Secretion and Cuticle Formation Transcriptional Regulation of Cuticle Production Chitin Synthesis Inhibitors Noncuticular Chitin in Insects Chitin as a Structural Element Application of Chitin Conclusion References
Correction: Spastic Paraplegia Mutation N256S in the Neuronal Microtubule Motor KIF5A Disrupts Axonal Transport in a Drosophila HSP Model
2013-04-15

Hereditary spastic paraplegias (HSPs) comprise a group of genetically heterogeneous neurodegenerative disorders characterized by spastic weakness of the lower extremities.We have generated a Drosophila model for HSP type 10 (SPG10), caused by mutations in KIF5A.KIF5A encodes the heavy chain of kinesin-1, a neuronal microtubule motor.Our results imply that SPG10 is not caused by haploinsufficiency but by the loss of endogenous kinesin-1 function due to a selective dominant-negative action of mutant KIF5A on kinesin-1 complexes.We have not found any evidence for an additional, more generalized toxicity of mutant Kinesin heavy chain (Khc) or the affected kinesin-1 complexes.Ectopic expression of Drosophila Khc carrying a human SPG10-associated mutation (N256S) is sufficient to disturb axonal transport and to induce motoneuron disease in Drosophila.Neurofilaments, which have been recently implicated in SPG10 disease manifestation, are absent in arthropods.Impairments in the transport of kinesin-1 cargos different from neurofilaments are thus sufficient to cause HSP-like pathological changes such as axonal swellings, altered structure and function of synapses, behavioral deficits, and increased mortality.
Global Dynamics of theEscherichia coliProteome and Phosphoproteome During Growth in Minimal Medium
2013-04-16

Recent phosphoproteomics studies have generated relatively large data sets of bacterial proteins phosphorylated on serine, threonine, and tyrosine, implicating this type of phosphorylation in the regulation of vital processes of a bacterial cell; however, most phosphoproteomics studies in bacteria were so far qualitative. Here we applied stable isotope labeling by amino acids in cell culture (SILAC) to perform a quantitative analysis of proteome and phosphoproteome dynamics of Escherichia coli during five distinct phases of growth in the minimal medium. Combining two triple-SILAC experiments, we detected a total of 2118 proteins and quantified relative dynamics of 1984 proteins in all measured phases of growth, including 570 proteins associated with cell wall and membrane. In the phosphoproteomic experiment, we detected 150 Ser/Thr/Tyr phosphorylation events, of which 108 were localized to a specific amino acid residue and 76 were quantified in all phases of growth. Clustering analysis of SILAC ratios revealed distinct sets of coregulated proteins for each analyzed phase of growth and overrepresentation of membrane proteins in transition between exponential and stationary phases. The proteomics data indicated that proteins related to stress response typically associated with the stationary phase, including RpoS-dependent proteins, had increasing levels already during earlier phases of growth. Application of SILAC enabled us to measure median occupancies of phosphorylation sites, which were generally low (<12%). Interestingly, the phosphoproteome analysis showed a global increase of protein phosphorylation levels in the late stationary phase, pointing to a likely role of this modification in later phases of growth.
From Soluble Aβ to Progressive Aβ Aggregation: Could Prion‐Like Templated Misfolding Play a Role?
2013-04-16

Abstract Accumulation, aggregation and deposition of A β peptides are pathological hallmarks in the brains of individuals affected by A lzheimer's disease ( AD ) or by cerebral β‐amyloid angiopathy ( A β‐ CAA ). While A β is a peptide of yet largely unknown function, it is constantly produced in the human brain where it normally remains in a soluble state. However, A β peptides are aggregation prone by their intrinsic ability to adopt alternative conformations rich in β‐sheet structure that aggregate into oligomeric as well as fibrillar formations. This transition from soluble to aggregated state has been hypothesized to initiate the pathological cascade and is therefore subject to intensive research. Mounting evidence suggests prion‐like templated misfolding as the biochemical phenomenon responsible for promoting progressive A β aggregation. Here, we review studies in vitro and in vivo that suggest that cerebral A β aggregation may indeed progress via prion‐like templated misfolding. The implications of these findings are discussed with respect to understanding initiation and progression of the disease and to developing therapeutics.
Interdisciplinary Climate Change Collaborations Are Essential for Early‐Career Scientists
2013-04-16

Climate change research is an interdisciplinary field, and understanding its social, political, and environmental implications requires integration across fields of research where different tools may be used to address common concerns [ Baerwald , 2010]. One of the many advantages of interdisciplinary approaches is that they open communication between complementary fields, filling knowledge gaps and facilitating progression within both individual fields and the broader field of climate change research [ Ludwig et al ., 2011].
On the Usage of Linear Regression Models to Reconstruct Limb Kinematics from Low Frequency EEG Signals
2013-04-17

Several works have reported on the reconstruction of 2D/3D limb kinematics from low-frequency EEG signals using linear regression models based on positive correlation values between the recorded and the reconstructed trajectories. This paper describes the mathematical properties of the linear model and the correlation evaluation metric that may lead to a misinterpretation of the results of this type of decoders. Firstly, the use of a linear regression model to adjust the two temporal signals (EEG and velocity profiles) implies that the relevant component of the signal used for decoding (EEG) has to be in the same frequency range as the signal to be decoded (velocity profiles). Secondly, the use of a correlation to evaluate the fitting of two trajectories could lead to overly-optimistic results as this metric is invariant to scale. Also, the correlation has a non-linear nature that leads to higher values for sinus/cosinus-like signals at low frequencies. Analysis of these properties on the reconstruction results was carried out through an experiment performed in line with previous studies, where healthy participants executed predefined reaching movements of the hand in 3D space. While the correlations of limb velocity profiles reconstructed from low-frequency EEG were comparable to studies in this domain, a systematic statistical analysis revealed that these results were not above the chance level. The empirical chance level was estimated using random assignments of recorded velocity profiles and EEG signals, as well as combinations of randomly generated synthetic EEG with recorded velocity profiles and recorded EEG with randomly generated synthetic velocity profiles. The analysis shows that the positive correlation results in this experiment cannot be used as an indicator of successful trajectory reconstruction based on a neural correlate. Several directions are herein discussed to address the misinterpretation of results as well as the implications on previous invasive and non-invasive works.
Malignant astrocytomas of elderly patients lack favorable molecular markers: an analysis of the NOA-08 study collective
2013-04-17

Despite an age-independent stable frequency of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation, tumors in this age group largely lack prognostically favorable markers established in younger glioblastoma patients, which likely contributes to the overall worse prognosis of elderly patients. However, the survival differences hint at fundamental further differences among malignant gliomas of different age groups.