julilili42/papers huggingface dataset:
p53 Regulates the Neuronal Intrinsic and Extrinsic Responses Affecting the Recovery of Motor Function following Spinal Cord Injury
2012-10-03

Following spinal trauma, the limited physiological axonal sprouting that contributes to partial recovery of function is dependent upon the intrinsic properties of neurons as well as the inhibitory glial environment. The transcription factor p53 is involved in DNA repair, cell cycle, cell survival, and axonal outgrowth, suggesting p53 as key modifier of axonal and glial responses influencing functional recovery following spinal injury. Indeed, in a spinal cord dorsal hemisection injury model, we observed a significant impairment in locomotor recovery in p53 −/− versus wild-type mice. p53 −/− spinal cords showed an increased number of activated microglia/macrophages and a larger scar at the lesion site. Loss- and gain-of-function experiments suggested p53 as a direct regulator of microglia/macrophages proliferation. At the axonal level, p53 −/− mice showed a more pronounced dieback of the corticospinal tract (CST) and a decreased sprouting capacity of both CST and spinal serotoninergic fibers. In vivo expression of p53 in the sensorimotor cortex rescued and enhanced the sprouting potential of the CST in p53 −/− mice, while, similarly, p53 expression in p53 −/− cultured cortical neurons rescued a defect in neurite outgrowth, suggesting a direct role for p53 in regulating the intrinsic sprouting ability of CNS neurons. In conclusion, we show that p53 plays an important regulatory role at both extrinsic and intrinsic levels affecting the recovery of motor function following spinal cord injury. Therefore, we propose p53 as a novel potential multilevel therapeutic target for spinal cord injury.
Signals from the Deep: Reach-Related Activity in the Human Superior Colliculus
2012-10-03

Neurophysiological studies in nonhuman species indicated that neurons in the superior colliculus (SC) are involved in the control of upper limb movements. These findings suggested that the SC represents a crucial hub in a general sensorimotor network, including skeletomotor as much as oculomotor functions. In contrast to the SC in the various animal models, the human SC is largely unknown territory. In particular, it is unknown whether findings of reach-related activity in the nonhuman SC can be extrapolated to humans. Using fMRI we found signal increases at superficial/intermediate and deep locations at the SC during the execution of arm movements. In contrast, signals related to saccade execution were confined to the superficial and intermediate locations. Although targets for reaching were presented in the left and right hemifields under central fixation, we found a lateralization of reach-related signals with respect to the active arm. In contrast, saccade-related activity was bilateral, in agreement with the bilateral target presentation and the resulting directions of saccades. Our results suggest that the human SC not only contributes to the coordination of eye movements and spatial shifts of attentions but also to the sensorimotor control of arm movements.
The Use of Primary Human Fibroblasts for Monitoring Mitochondrial Phenotypes in the Field of Parkinson's Disease
2012-10-03

Parkinson's disease (PD) is the second most common movement disorder and affects 1% of people over the age of 60 (1). Because ageing is the most important risk factor, cases of PD will increase during the next decades (2). Next to pathological protein folding and impaired protein degradation pathways, alterations of mitochondrial function and morphology were pointed out as further hallmark of neurodegeneration in PD (3-11). After years of research in murine and human cancer cells as in vitro models to dissect molecular pathways of Parkinsonism, the use of human fibroblasts from patients and appropriate controls as ex vivo models has become a valuable research tool, if potential caveats are considered. Other than immortalized, rather artificial cell models, primary fibroblasts from patients carrying disease-associated mutations apparently reflect important pathological features of the human disease. Here we delineate the procedure of taking skin biopsies, culturing human fibroblasts and using detailed protocols for essential microscopic techniques to define mitochondrial phenotypes. These were used to investigate different features associated with PD that are relevant to mitochondrial function and dynamics. Ex vivo, mitochondria can be analyzed in terms of their function, morphology, colocalization with lysosomes (the organelles degrading dysfunctional mitochondria) and degradation via the lysosomal pathway. These phenotypes are highly relevant for the identification of early signs of PD and may precede clinical motor symptoms in human disease-gene carriers. Hence, the assays presented here can be utilized as valuable tools to identify pathological features of neurodegeneration and help to define new therapeutic strategies in PD.
Resolving a mammal mystery: the identity of Paracoelops megalotis (Chiroptera: Hipposideridae)
2012-10-03

Paracoelops has been regarded as monotypic and an endemic bat genus of Vietnam. In the original description of 1947,P. megalotis was characterised by its exceptionally large ears and well developed interfemoral membrane without a tail.The status of this taxon remained uncertain since the species and genus descriptions were based on the single, badly dam-aged holotype. Recently, we re-examined the holotype and found discrepancies between its features and those describedin the diagnoses. Its measurements and characteristics are entirely identical to those of a small species of Hipposideros.Having compared its features with those of other hipposiderids, we show here that Paracoelops megalotis was incorrectly classified both in terms of genus and species and should be considered a synonym of Hipposideros pomona.
The Use of Primary Human Fibroblasts for Monitoring Mitochondrial Phenotypes in the Field of Parkinson's Disease
2012-10-03

Parkinson's disease (PD) is the second most common movement disorder and affects 1% of people over the age of 60 1. Because ageing is the most important risk factor, cases of PD will increase during the next decades 2. Next to pathological protein folding and impaired protein degradation pathways, alterations of mitochondrial function and morphology were pointed out as further hallmark of neurodegeneration in PD 3-11. After years of research in murine and human cancer cells as in vitro models to dissect molecular pathways of Parkinsonism, the use of human fibroblasts from patients and appropriate controls as ex vivo models has become a valuable research tool, if potential caveats are considered. Other than immortalized, rather artificial cell models, primary fibroblasts from patients carrying disease-associated mutations apparently reflect important pathological features of the human disease. Here we delineate the procedure of taking skin biopsies, culturing human fibroblasts and using detailed protocols for essential microscopic techniques to define mitochondrial phenotypes. These were used to investigate different features associated with PD that are relevant to mitochondrial function and dynamics. Ex vivo, mitochondria can be analyzed in terms of their function, morphology, colocalization with lysosomes (the organelles degrading dysfunctional mitochondria) and degradation via the lysosomal pathway. These phenotypes are highly relevant for the identification of early signs of PD and may precede clinical motor symptoms in human disease-gene carriers. Hence, the assays presented here can be utilized as valuable tools to identify pathological features of neurodegeneration and help to define new therapeutic strategies in PD.
An RNA–Deaminase Conjugate Selectively Repairs Point Mutations
2012-10-04

Checking for mistakes: By conjugating a catalytic domain with a guide RNA, deamination activity can be harnessed to repair a specific codon on mRNA. This method can be used for the highly selective repair of point mutations in mRNA by site-selective editing.
Unique genes identified in the epidemic extremely drug-resistant KPC-producing Klebsiella pneumoniae sequence type 258
2012-10-04

This study identifies unique genes in ST258 bacteria that may contribute to its epidemiological success as compared with other KPC-producing STs. Conservation of plasmid-encoded genes among ST258 isolates, despite plasmid variation, supports their importance in the success of this clone.
Spectral Discrimination of Cerebral Amyloid Lesions after Peripheral Application of Luminescent Conjugated Oligothiophenes
2012-10-04

In vivo imaging of pathological protein aggregates provides essential knowledge of the kinetics and implications of these lesions in the progression of proteopathies, such as Alzheimer disease. Luminescent conjugated oligothiophenes are amyloid-specific ligands that bind and spectrally distinguish different types of amyloid aggregates. Herein, we report that heptamer formyl thiophene acetic acid (hFTAA) passes the blood-brain barrier after systemic administration and specifically binds to extracellular β-amyloid deposits in the brain parenchyma (Aβ plaques) and in the vasculature (cerebral β-amyloid angiopathy) of β-amyloid precursor protein transgenic APP23 mice. Moreover, peripheral application of hFTAA also stained intracellular lesions of hyperphosphorylated Tau protein in P301S Tau transgenic mice. Spectral profiling of all three amyloid types was acquired ex vivo using two-photon excitation. hFTAA revealed a distinct shift in its emission spectra when bound to Aβ plaques versus Tau lesions. Furthermore, a spectral shift was observed for Aβ plaques versus cerebral β-amyloid angiopathy, indicating that different amyloid types and structural variances of a specific amyloid type can be distinguished. In conclusion, by adding spectral signatures to amyloid lesions, our results pave the way for a new area of in vivo amyloid imaging, allowing in vivo differentiation of amyloid (sub)types and monitoring changes of their structure/composition over time.
Reactivity of Borylenes toward Ethyne, Ethene, and Methane
2012-10-04

The electronic and geometric structure of various substituted borylenes BR (where R = H, F, Cl, Br, CH(3), Ph, NH(2), NHMe, and NMe(2)) in their lowest singlet and triplet electronic states was investigated by computational means using hybrid density functional (B3LYP) and second-order Møller-Plesset perturbation theories combined with 6-311+G** and cc-pVTZ basis sets. The reactivity of singlet borylenes towards prototypical saturated and unsaturated hydrocarbons was examined by the MP2 method in conjugation with the cc-pVTZ basis set and also by coupled cluster [CCSD(T)] computations in combination with the aug-cc-pVTZ basis set. To study the energetics and the mechanism of the addition reaction of borylenes to unsaturated CC bonds, ethyne and ethene are chosen as model compounds. The insertion reaction of borylene into a C-H bond of methane was also investigated. The addition reactions of borylenes to multiple C-C bonds are strongly exothermic. In case of the BH molecule the reactions proceed without barrier and are the most exothermic. For the insertion reaction of borylenes into methane, two approaches could be identified. Again, the smallest reaction barriers and highest reaction energies were computed for the BH insertion, while the highest barriers and the smallest exothermicities were obtained for the BF molecule. On the basis of frontier molecular orbital energies, barrier heights, reaction energies, and transition state geometries BH is the most electrophilic borylene, followed by BPh, while aminoborylenes and BF are the most nucleophilic ones among the investigated derivatives. Accordingly, reactions of BH have the smallest barriers (if there is one at all) and the largest reaction energies, while the reactions of BF have the highest barriers and the smallest reaction energies.
The bifunctional role of aconitase in S treptomyces viridochromogenes T ü494
2012-10-04

Summary In many organisms, aconitases have dual functions; they serve as enzymes in the tricarboxylic acid cycle and as regulators of iron metabolism. In this study we defined the role of the aconitase AcnA in S treptomyces viridochromogenes T ü494, the producer of the herbicide phosphinothricyl‐alanyl‐alanine, also known as phosphinothricin tripeptide or bialaphos. A mutant in which the aconitase gene acnA was disrupted showed severe defects in morphology and physiology, as it was unable to form any aerial mycelium, spores nor phosphinothricin tripeptide. AcnA belongs to the iron regulatory proteins ( IRP s). In addition to its catalytic function, AcnA plays a regulatory role by binding to iron responsive elements ( IRE s) located on the untranslated region of certain mRNA s. A mutation preventing the formation of the [4 Fe ‐4 S ] cluster of AcnA eliminated its catalytic activity, but did not inhibit RNA ‐binding ability. In silico analysis of the S . viridochromogenes genome revealed several IRE ‐like structures. One structure is located upstream of recA , which is involved in the bacterial SOS response, and another one was identified upstream of ftsZ , which is required for the onset of sporulation in streptomycetes. The functionality of different IRE structures was proven with gel shift assays and specific IRE consensus sequences were defined. Furthermore, RecA was shown to be upregulated on post‐transcriptional level under oxidative stress conditions in the wild‐type strain but not in the acnA mutant, suggesting a regulatory role of AcnA in oxidative stress response.
Assessing the plasmonics of gold nano-triangles with higher order laser modes
2012-10-04

Regular arrays of metallic nano-triangles – so called Fischer patterns – are fabricated by nano-sphere lithography. We studied such gold nano-triangle arrays on silicon or glass substrates. A series of different samples was investigated with a parabolic mirror based confocal microscope where the sample is scanned through the laser focus. By employing higher order laser modes (azimuthally and radially polarised laser beams), we can excite the Fischer patterns using either a pure in-plane (x,y) electric field or a strongly z-directional (optical axis of the optical microscope) electric field. We collected and evaluated the emitted luminescence and thereby investigated the respectively excited plasmonic modes. These varied considerably: firstly with the light polarisation in the focus, secondly with the aspect ratio of the triangles and thirdly with the employed substrate. Moreover, we obtained strongly enhanced Raman spectra of an adenine (sub-)monolayer on gold Fischer patterns on glass. We thus showed that gold Fischer patterns are promising surface-enhanced Raman scattering (SERS) substrates.
Tax Evasion and Tacit Collusion
2012-10-04

This article analyzes the interaction between tax evasion and tacit collusion. We show that the possibility of evading taxes generally influences the incentives to form a cartel. We establish that whether tax evasion increases or decreases the set of circumstances allowing stable collusion depends on (1) the relation between the benefits of tax evasion and legal after-tax profits and (2) effective enforcement of antitrust laws. In considering variations in tax enforcement and antitrust enforcement, we find that stricter tax enforcement may actually increase the level of tax evasion, as it may promote the cartelization of industries. In contrast, stricter antitrust enforcement lowers incentives for cartelization, thereby possibly reducing tax evasion at the same time.
Pyramid array substrates for biomedical studies
2012-10-04

Cellular reactions to structured surfaces are the subject of intense studies in biomedical research, e.g., for implant technology. Substrates with well-defined structures in relevant materials such as titanium (Ti) are required for these investigations. The pyramidal arrays presented here offer very sharp edges and tips, which appeared to be the main adhesion spots in our earlier cell-surface-interaction studies. Using an etch process based on anisotropic etching of silicon in alkaline solution, the shape of the pyramids is strictly determined by the crystal structure of silicon, while the height as well as the pitch of the pyramids can be precisely controlled and, therefore, be varied in a systematic fashion. Being made from silicon nitride with a thin cover layer of titanium, they offer mechanical stiffness, inertness to all chemicals used in the cell experiments, and a high degree of biocompatibility.
Proprioceptive Feedback and Brain Computer Interface (BCI) Based Neuroprostheses
2012-10-05

Brain computer interface (BCI) technology has been proposed for motor neurorehabilitation, motor replacement and assistive technologies. It is an open question whether proprioceptive feedback affects the regulation of brain oscillations and therefore BCI control. We developed a BCI coupled on-line with a robotic hand exoskeleton for flexing and extending the fingers. 24 healthy participants performed five different tasks of closing and opening the hand: (1) motor imagery of the hand movement without any overt movement and without feedback, (2) motor imagery with movement as online feedback (participants see and feel their hand, with the exoskeleton moving according to their brain signals, (3) passive (the orthosis passively opens and closes the hand without imagery) and (4) active (overt) movement of the hand and rest. Performance was defined as the difference in power of the sensorimotor rhythm during motor task and rest and calculated offline for different tasks. Participants were divided in three groups depending on the feedback receiving during task 2 (the other tasks were the same for all participants). Group 1 (n = 9) received contingent positive feedback (participants' sensorimotor rhythm (SMR) desynchronization was directly linked to hand orthosis movements), group 2 (n = 8) contingent "negative" feedback (participants' sensorimotor rhythm synchronization was directly linked to hand orthosis movements) and group 3 (n = 7) sham feedback (no link between brain oscillations and orthosis movements). We observed that proprioceptive feedback (feeling and seeing hand movements) improved BCI performance significantly. Furthermore, in the contingent positive group only a significant motor learning effect was observed enhancing SMR desynchronization during motor imagery without feedback in time. Furthermore, we observed a significantly stronger SMR desynchronization in the contingent positive group compared to the other groups during active and passive movements. To summarize, we demonstrated that the use of contingent positive proprioceptive feedback BCI enhanced SMR desynchronization during motor tasks.
Improved glycaemic control with vildagliptin added to insulin, with or without metformin, in patients with type 2 diabetes mellitus
2012-10-05

Aim The aim of this study is to assess the efficacy and safety of vildagliptin 50 mg bid as add‐on therapy to insulin in type 2 diabetes mellitus ( T2DM ). Methods This is a multicentre, double‐blind, placebo‐controlled, parallel group, clinical trial in T2DM patients inadequately controlled by stable insulin therapy, with or without metformin. Patients received treatment with vildagliptin 50 mg bid or placebo for 24 weeks. Results In all, 449 patients were randomized to vildagliptin (n = 228) or placebo (n = 221). After 24 weeks, the difference in adjusted mean change in haemoglobin A1c ( HbA1c ) between vildagliptin and placebo was −0.7 ± 0.1% (p &lt; 0.001) in the overall study population, −0.6 ± 0.1% (p &lt; 0.001) in the subgroup also receiving metformin and −0.8 ± 0.2% (p &lt; 0.001) in the subgroup without metformin. Vildagliptin therapy was well tolerated and had a similarly low incidence of hypoglycaemia compared with placebo (8.4 vs. 7.2%, p = 0.66) in spite of improved glycaemic control, and was not associated with weight gain. (+0.1 vs. −0.4 kg). Conclusions Vildagliptin 50 mg bid added to insulin significantly reduced HbA1c in patients with T2DM inadequately controlled by insulin, with or without metformin. Vildagliptin was well tolerated, with a safety profile similar to placebo. These results were achieved without weight gain or an increase in hypoglycaemia incidence or severity in spite of improved glycaemic control.
Utilization of Sialylated Glycans as Coreceptors Enhances the Neurovirulence of Serotype 3 Reovirus
2012-10-05

ABSTRACT Mammalian reoviruses display serotype-specific patterns of tropism and disease in the murine central nervous system (CNS) attributable to polymorphisms in viral attachment protein σ1. While all reovirus serotypes use junctional adhesion molecule-A as a cellular receptor, they differ in their utilization of carbohydrate coreceptors. This observation raises the possibility that carbohydrate binding by σ1 influences reovirus pathology in the CNS. In this study, we sought to define the function of carbohydrate binding in reovirus neuropathogenesis. Newborn mice were inoculated intramuscularly with wild-type strain type 3 Dearing (T3D) and T3D-σ1R202W, a point mutant T3D derivative that does not bind sialic acid (SA). Infected mice were monitored for survival, and viral loads at the sites of primary and secondary replication were quantified. Fewer mice inoculated with the wild-type virus survived in comparison to those inoculated with the mutant virus. The wild-type virus also produced higher titers in the spinal cord and brain at late times postinoculation but lower titers in the liver in comparison to those produced by the mutant virus. In addition, the wild-type virus was more virulent and produced higher titers in the brain than the mutant following intracranial inoculation. These animal infectivity studies suggest that T3D-σ1R202W harbors a defect in neural growth. Concordantly, compared with the wild-type virus, the mutant virus displayed a decreased capacity to infect and replicate in primary cultures of cortical neurons, a property dependent on cell surface SA. These results suggest that SA binding enhances the kinetics of reovirus replication in neural tissues and highlight a functional role for sialylated glycans as reovirus coreceptors in the CNS.
Role of Mie scattering in the seeding of matter-wave superradiance
2012-10-05

Matter-wave superradiance is based on the interplay between ultracold atoms\\ncoherently organized in momentum space and a backscattered wave. Here, we show\\nthat this mechanism may be triggered by Mie scattering from the atomic cloud.\\nWe show how the laser light populates the modes of the cloud, and thus imprints\\na phase gradient on the excited atomic dipoles. The interference with the atoms\\nin the ground state results in a grating, that in turn generates coherent\\nemission, contributing to the backward light wave onset. The atomic recoil\\n'halos' created by the scattered light exhibit a strong anisotropy, in contrast\\nto single-atom scattering.\\n