julilili42/papers huggingface dataset:
Neurodegenerative Diseases: Expanding the Prion Concept
2015-04-04

The prion paradigm has emerged as a unifying molecular principle for the pathogenesis of many age-related neurodegenerative diseases. This paradigm holds that a fundamental cause of specific disorders is the misfolding and seeded aggregation of certain proteins. The concept arose from the discovery that devastating brain diseases called spongiform encephalopathies are transmissible to new hosts by agents consisting solely of a misfolded protein, now known as the prion protein. Accordingly, “prion” was defined as a “proteinaceous infectious particle.” As the concept has expanded to include other diseases, many of which are not infectious by any conventional definition, the designation of prions as infectious agents has become problematic. We propose to define prions as “proteinaceous nucleating particles” to highlight the molecular action of the agents, lessen unwarranted apprehension about the transmissibility of noninfectious proteopathies, and promote the wider acceptance of this revolutionary paradigm by the biomedical community.
Triple‐quantum‐filtered sodium imaging at 9.4 Tesla
2015-04-04

Purpose Efficient acquisition of triple‐quantum‐filtered (TQF) sodium images at ultra‐high field (UHF) strength. Methods A three‐pulse preparation and a stack of double‐spirals were used for the acquisition of TQF images at 9.4 Tesla. The flip angles of the TQ preparation were smoothly reduced toward the edge of k‐space along the partition‐encoding direction. In doing so, the specific absorption rate could be reduced while preserving the maximal signal intensity for the partitions most relevant for image contrast in the center of k‐space. Simulations, phantom and in vivo measurements were used to demonstrate the usefulness of the proposed method. Results A higher sensitivity (∼20%) was achieved compared to the standard acquisition without flip angle apodization. Signals from free sodium ions were successfully suppressed irrespective of the amount of apodization used. B 0 corrected TQF images with a nominal resolution of 5 × 5 × 5 mm 3 and an acceptable signal‐to‐noise ratio could be acquired in vivo within 21 min. Conclusion Conventional TQF in combination with flip angle apodization permits to exploit more efficiently the increased sensitivity available at 9.4T. Magn Reson Med 75:1278–1289, 2016. © 2015 Wiley Periodicals, Inc.
Immune evasion in cancer: Mechanistic basis and therapeutic strategies
2015-04-05

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.
Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation
2015-04-05

Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases.
Safety testing and operational procedures for self‐developed radiofrequency coils
2015-04-06

The development of novel radiofrequency (RF) coils for human ultrahigh‐field (≥7 T), non‐proton and body applications is an active field of research in many MR groups. Any RF coil must meet the strict requirements for safe application on humans with respect to mechanical and electrical safety, as well as the specific absorption rate (SAR) limits. For this purpose, regulations such as the International Electrotechnical Commission (IEC) standard for medical electrical equipment, vendor‐suggested test specifications for third party coils and custom‐developed test procedures exist. However, for higher frequencies and shorter wavelengths in ultrahigh‐field MR, the RF fields may become extremely inhomogeneous in biological tissue and the risk of localized areas with elevated power deposition increases, which is usually not considered by existing safety testing and operational procedures. In addition, important aspects, such as risk analysis and comprehensive electrical performance and safety tests, are often neglected. In this article, we describe the guidelines used in our institution for electrical and mechanical safety tests, SAR simulation and verification, risk analysis and operational procedures, including coil documentation, user training and regular quality assurance testing, which help to recognize and eliminate safety issues during coil design and operation. Although the procedure is generally applicable to all field strengths, specific requirements with regard to SAR‐related safety and electrical performance at ultrahigh‐field are considered. The protocol describes an internal procedure and does not reflect consensus among a large number of research groups, but rather aims to stimulate further discussion related to minimum coil safety standards. Furthermore, it may help other research groups to establish their own procedures. Copyright © 2015 John Wiley &amp; Sons, Ltd.
Alpha-Synuclein Levels in Blood Plasma Decline with Healthy Aging
2015-04-06

There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.
Preference for Cute Infants Does Not Depend on Their Ethnicity or Species: Evidence from Hypothetical Adoption and Donation Paradigms
2015-04-06

Results of previous work suggest a preference of adult observers for cute compared to less cute infants. In Study 1 we investigated whether the preference for cute infants depends on the ethnicity and species of the infant. We simultaneously presented two faces (one cute and one less cute) and asked Caucasian participants to choose the infant to whom they would rather give a toy (Task 1) and which infant they would rather adopt (Task 2). The infants were Caucasian or African human babies or dog puppies. For all face categories and in both tasks we found a strong preference for cute infants. A possible reason for preferring cute infants may be that cute infants look healthier than less cute infants. To investigate whether cuteness is associated with the assessment of health we conducted Study 2. Faces of Caucasian and African infants and dog puppies were rated for cuteness and health. The findings revealed a significant relationship between health and cuteness evaluation across all stimuli. We suggest that one reason why cute infants are preferred might be because they are perceived as being healthier.
Specific synaptopathies diversify brain responses and hearing disorders: you lose the gain from early life
2015-04-06

Before hearing onset, inner hair cell (IHC) maturation proceeds under the influence of spontaneous Ca(2+) action potentials (APs). The temporal signature of the IHC Ca(2+) AP is modified through an efferent cholinergic feedback from the medial olivocochlear bundle (MOC) and drives the IHC pre- and post-synapse phenotype towards low spontaneous (spike) rate (SR), high-threshold characteristics. With sensory experience, the IHC pre- and post-synapse phenotype matures towards the instruction of low-SR, high-threshold and of high-SR, low-threshold auditory fiber characteristics. Corticosteroid feedback together with local brain-derived nerve growth factor (BDNF) and catecholaminergic neurotransmitters (dopamine) might be essential for this developmental step. In this review, we address the question of whether the control of low-SR and high-SR fiber characteristics is linked to various degrees of vulnerability of auditory fibers in the mature system. In particular, we examine several IHC synaptopathies in the context of various hearing disorders and exemplified shortfalls before and after hearing onset.
Boucher Neuhäuser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism - two novel cases and a review of 40 cases from the literature (P2.110)
2015-04-06

Objective: The combination of progressive cerebellar degeneration, hypogonadotropic hypogonadism and chorioretinal dystrophy defines the rare Boucher-Neuhäuser Syndrome (BNS), which has recently been linked to autosomal recessive mutations in the PNPLA6 gene in four index patients. Background: Here we present two novel index patients with BNS, providing both clinical information and genetic testing. In addition, the literature of previously published BNS cases is reviewed. Methods: Detailed neurological, ophthalmological and endocrinological assessment was performed in both index cases. A targeted high-throughput approach was used to search for PNPLA6 mutations. The spectrum of clinical presentations and phenotype evolution of BNS based on our two index cases and a MEDLINE search for publications related to BNS was then summarized. Results: We identified 4 recessive PNPLA6 mutations as the genetic cause in our two index cases, highlighting PNPLA6 as the major gene leading to BNS. The literature search identified 40 cases that fulfilled the clinical criteria for BNS. Both our two index patients and the previously published cases propose that the clinical presentation of BNS is variable regarding disease severity, age (range=1-40y) and clinical symptoms (cerebellar ataxia=38[percnt]; vision loss=36[percnt]; delayed puberty=26[percnt]) at disease onset. On brain MRI relatively selective atrophy of the superior and dorsal parts of the cerebellar vermis along with atrophy of the cerebellar hemispheres was found in a substantial fraction of BNS cases. Conclusions: Albeit defined clinically by the combination of spinocerebellar ataxia, chorioretinal degeneration and hypogonadotropic hypogonadism, BNS varies substantially in disease onset, clinical presentation and progression. Thus, a thorough assessment for ophthalmological, neurological and endocrinological changes in patients presenting with one of the key features is recommended. With PNPLA6 likely causing the large majority of BNS cases, future identification of the underlying gene defect will be facilitated.
Rapidly rotating neutron stars inR-squared gravity
2015-04-07

theories of gravity are one of the most popular alternative explanations for dark energy and therefore studying the possible astrophysical implications of these theories is an important task. In the present paper we make a substantial advance in this direction by considering rapidly rotating neutron stars in gravity. The results are obtained numerically and the method we use is non-perturbative and self-consistent. The neutron star properties, such as mass, radius and moment of inertia, are studied in detail and the results show that rotation magnifies the deviations from general relativity and the maximum mass and moment of inertia can reach very high values. This observation is similar to previous studies of rapidly rotating neutron stars in other alternative theories of gravity, such as the scalar-tensor theories, and it can potentially lead to strong astrophysical manifestations.
Heart rate variability parameters and fetal movement complement fetal behavioral states detection via magnetography to monitor neurovegetative development
2015-04-07

Fetal behavioral states are defined by fetal movement and heart rate variability (HRV). At 32 weeks of gestational age (GA) the distinction of four fetal behavioral states represented by combinations of quiet or active sleep or awakeness is possible. Prior to 32 weeks, only periods of fetal activity and quiesence can be distinguished. The increasing synchronization of fetal movement and HRV reflects the development of the autonomic nervous system (ANS) control. Fetal magnetocardiography (fMCG) detects fetal heart activity at high temporal resolution, enabling the calculation of HRV parameters. This study combined the criteria of fetal movement with the HRV analysis to complete the criteria for fetal state detection. HRV parameters were calculated including the standard deviation of the normal-to-normal R-R interval (SDNN), the mean square of successive differences of the R-R intervals (RMSSD, SDNN/RMSSD ratio, and permutation entropy (PE) to gain information about the developing influence of the ANS within each fetal state. In this study, 55 magnetocardiograms from healthy fetuses of 24-41 weeks' GA were recorded for up to 45 min using a fetal biomagnetometer. Fetal states were classified based on HRV and movement detection. HRV parameters were calculated for each state. Before GA 32 weeks, 58.4% quiescence and 41.6% activity cycles were observed. Later, 24% quiet sleep state (1F), 65.4% active sleep state (2F), and 10.6% active awake state (4F) were observed. SDNN increased over gestation. Changes of HRV parameters between the fetal behavioral states, especially between 1F and 4F, were statistically significant. Increasing fetal activity was confirmed by a decrease in PE complexity measures. The fHRV parameters support the differentiation between states and indicate the development of autonomous nervous control of heart rate function.
CCR4+Regulatory T Cells Accumulate in the Very Elderly and Correlate With Superior 8-Year Survival
2015-04-07

CD4(+) regulatory T cells (Tregs) are a distinct population of T cells involved in maintaining peripheral tolerance to self-antigens. Several studies have shown increased frequency and number of Tregs in the elderly. Whether such an increase has any clinical relevance has not been addressed. Here, we have analyzed circulating Tregs in 114 donors between the ages of 18 and 89 years and assessed their implications for survival of the very elderly. In line with previously published data, we observed higher proportions of Tregs in the elderly. Expression of chemokine receptor 4 (CCR4) by Tregs has been shown to characterize antigen-primed activated Tregs with immediate suppressive function. Thus we further analyzed Tregs expressing or lacking this chemokine receptor. There were more CCR4(+) and CCR4(-) Tregs in the elderly than the young. Finally, using a subset of 48 elderly donors participating in the Leiden 85-plus study we documented that people with greater median frequencies of CCR4(+) Tregs enjoyed a better 8-year survival rate than those with lower frequencies of these cells. Our data, demonstrating for the first time a positive correlation between increased frequency of Tregs and survival in the elderly, imply an increasing importance of controlling inappropriate immune responses and inflammation as we grew old.
Attracted to power: challenge/threat and promotion/prevention focus differentially predict the attractiveness of group power
2015-04-07

Depending on their motivation, individuals prefer different group contexts for social interactions. The present research sought to provide more insight into this relationship. More specifically, we tested how challenge/threat and a promotion/prevention focus predict attraction to groups with high- or low-power. As such, we examined differential outcomes of threat and prevention focus as well as challenge and promotion focus that have often been regarded as closely related. According to regulatory focus, individuals should prefer groups that they expect to “feel right” for them to join: Low-power groups should be more attractive in a prevention (than a promotion) focus, as these groups suggest security-oriented strategies, which fit a prevention focus. High-power groups should be more attractive in a promotion (rather than a prevention) focus, as these groups are associated with promotion strategies fitting a promotion focus (Sassenberg et al., 2007). In contrast, under threat (vs. challenge), groups that allow individuals to restore their (perceived) lack of control should be preferred: Low-power groups should be less attractive under threat (than challenge) because they provide low resources which threatened individuals already perceive as insufficient and high-power groups might be more attractive under threat (than under challenge), because their high resources allow individuals to restore control. Two experiments (N = 140) supported these predictions. The attractiveness of a group often depends on the motivation to engage in what fits (i.e., prefer a group that feels right in the light of one’s regulatory focus). However, under threat the striving to restore control (i.e., prefer a group allowing them to change the status quo under threat vs. challenge) overrides the fit effect, which may in turn guide individuals’ behavior in social interactions.
Banking Globalization
2015-04-07

Abstract The 2007–09 financial crisis has renewed interest in the causes of consequences of international bank mergers. While it is too early to assess the effects of recent developments on financial markets, there is a rich literature on international mergers and acquisitions in banking, which this chapter surveys. We focus on three main questions. First, what are the determinants of cross-border acquisitions of commercial banks? Second, do cross-border acquisitions affect the efficiency of banks? Third, what are the risk effects of international bank acquisitions? We begin with a brief summary of the stylized facts, and we conclude with implications for policymakers.
Secondary Mineral Formation During Ferrihydrite Reduction byShewanella oneidensisMR-1 Depends on Incubation Vessel Orientation and Resulting Gradients of Cells, Fe2+and Fe Minerals
2015-04-08

In previous studies on microbial ferric iron (Fe(III)) reduction varying results regarding reduction rates and secondary mineral formation have been reported for almost identical conditions regarding temperature, pH, medium composition, Fe(III) mineral identity and bulk iron concentration. Here we show that in addition to physico-chemical parameters also geometric aspects, i.e., incubation orientation and dimension of cultivation vessels, influence the reduction rates and mineralogy. We incubated the Fe(III)-reducer Shewanella oneidensis MR-1 in test tubes at ferrihydrite (FH) concentrations of 1.3–50 mM either in vertical or horizontal orientation. Cells and minerals formed a pellet at the bottom of the tubes with different thicknesses at the same initial FH concentration depending on the incubation orientation. In vertically incubated tubes thick FH pellets were present at the bottom of the tubes and magnetite was formed in all setups with ≥2.5 mM initial FH. In tubes that were incubated horizontally no magnetite was formed in presence of <5 mM initial FH. Spatially resolved analysis of the supernatant and mineral sediment including voltammetric microelectrodes, Xray diffraction and Mössbauer spectroscopy revealed strong gradients of Fe2+ in both the aqueous supernatant and mineral pellets, whereas a heterogeneous distribution of cells and minerals in the sediment pellet was detected. The highest cell density and, consequently, the initiation of FH reduction was found at the mineral-supernatant interface. This study demonstrates that small changes in incubation conditions can significantly influence and even change the experimental results of geomicrobiological experiments.
Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition
2015-04-08

Abstract Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterized high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas datasets were also used to assess the correlation between gene expression, patient survival, and tumor classification. In a multivariate analysis, high GAB2 expression was associated with improved overall and progression-free survival (P = 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy number gain were enriched in the AOCS C4 subgroup. High GAB2 expression correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF-04691502 and could be used as a genomic marker for identifying patients who will respond to treatments inhibiting PI3K signaling. Mol Cancer Ther; 14(6); 1495–503. ©2015 AACR.