julilili42/papers huggingface dataset:
An Interaction Network of RNA-Binding Proteins Involved in Drosophila Oogenesis
2020-06-17

During <i>Drosophila</i> oogenesis, the localization and translational regulation of maternal transcripts relies on RNA-binding proteins (RBPs). Many of these RBPs localize several mRNAs and may have additional direct interaction partners to regulate their functions. Using immunoprecipitation from whole <i>Drosophila</i> ovaries coupled to mass spectrometry, we examined protein-protein associations of 6 GFP-tagged RBPs expressed at physiological levels. Analysis of the interaction network and further validation in human cells allowed us to identify 26 previously unknown associations, besides recovering several well characterized interactions. We identified interactions between RBPs and several splicing factors, providing links between nuclear and cytoplasmic events of mRNA regulation. Additionally, components of the translational and RNA decay machineries were selectively co-purified with some baits, suggesting a mechanism for how RBPs may regulate maternal transcripts. Given the evolutionary conservation of the studied RBPs, the interaction network presented here provides the foundation for future functional and structural studies of mRNA localization across metazoans.
Against Repurposing Methadone for Glioblastoma Therapy
2020-06-17

Methadone, which is used as maintenance medication for outpatient treatment of opioid dependence or as an analgesic drug, has been suggested by preclinical in vitro and mouse studies to induce cell death and sensitivity to chemo- or radiotherapy in leukemia, glioblastoma, and carcinoma cells. These data together with episodical public reports on long-term surviving cancer patients who use methadone led to a hype of methadone as an anti-cancer drug in social and public media. However, clinical evidence for a tumoricidal effect of methadone is missing and prospective clinical trials, except in colorectal cancer, are not envisaged because of the limited preclinical data available. The present article reviews the pharmacokinetics, potential molecular targets, as well as the evidence for a tumoricidal effect of methadone in view of the therapeutically achievable doses in the brain. Moreover, it provides original in vitro data showing that methadone at clinically relevant concentrations fails to impair clonogenicity or radioresistance of glioblastoma cells.
Metalated Porphyrin Stable Free Radicals: Exploration of Electron Spin Communication and Dynamics
2020-06-17

Switchable coupling between two qubits is important for quantum information science (QIS). As a proof of concept, a series of mesosubstituted porphyrins have been synthesized with a (2,2,6,6-tetramethylpiperidin-1-yl)oxyl stable free radical (SFR) appended and metalated with Cu(II), Ni(II), and Zn(II) in order to explore the interaction between the SFR doublet state and metalloporphyrin. The spin state of the porphyrin varies upon metal insertion, where Zn(II) is a diamagnetic metal, Cu(II) is paramagnetic, and Ni(II) can be switched from a diamagnetic square-planar structure to a paramagnetic octahedral state by complexation with a solvent (i.e., pyridine or tetrahydrofuran). Time-resolved electron paramagnetic resonance (EPR) measurements reveal that upon photoexcitation, the Zn(II) and free-base porphyrin species demonstrate different magnetic exchange regimes between the porphyrin triplet excited states and the SFR doublet state, with the Zn derivative populating a quartet state (i.e., moderate magnetic exchange), whereas the free-base derivative remains a triplet (i.e., weak magnetic exchange). Transient absorption measurements corroborate the TREPR results, demonstrating a 66% increase in the singlet excited-state decay rate due to enhanced intersystem crossing for the Zn(II) derivative in comparison to a modest 14% enhancement for the free-base porphyrin. These results enable the realization of a switchable qubit coupler, depending upon Zn metal insertion to the free-base porphyrin, which has potential QIS applications.
Electroencephalography of completely locked-in state patients with amyotrophic lateral sclerosis
2020-06-17

The data set includes raw EEG data for 10 completely locked-in state (CLIS) patients with amyotrophic lateral sclerosis (ALS) and 6 healthy participants. The EEG data were recorded during resting state and the reference was right mastoid. This data was used in the publication https://doi.org/10.1016/j.neures.2020.01.013.
Comparing Effectiveness of HRV-Biofeedback and Mindfulness for Workplace Stress Reduction: A Randomized Controlled Trial
2020-06-18

Abstract Psychophysiological disorders due to work-related stress continue to be highly costly for health systems and approaches for cost-effective and easily accessible interventions are much needed. Both heart rate variability-biofeedback (HRV-Bfb) and mindfulness-based interventions (MBI) have been empirically shown to reduce stress. This study compares these two interventions in the work context to a wait-list-control-group (WLC). In this three-armed randomized controlled trial (RCT), 69 healthy adults employed in the same organization were randomized to participate in HRV-Bfb, MBI or the WLC. Participants were assessed for psychophysiological parameters of stress (stress perception, coping, HRV parameters and cortisol) and stress related symptoms (depressive symptoms, psychological wellbeing, mindfulness and self-compassion). Participants trained using either HRV-Bfb or MBI for 6 weeks on a daily basis. Outcomes were assessed at baseline, after the intervention and at follow-up 12 weeks later. Results did not show any statistically significant differences between HRV-Bfb and MBI groups, and neither of the intervention groups (IGs) differed from the WLC. Findings suggest an overall reduction in stress for all groups, including the WLC, with mostly small to medium effect sizes. However, it is important to note that participants with higher baseline stress levels might benefit more from mindfulness and biofeedback-based stress reduction interventions. The results have to be interpreted with caution due to the relatively small sample size. MBI might have a slightly stronger effect on stress reduction in comparison to HRV-Bfb, as suggested by the effect sizes. This study highlights issues and challenges of the implementation of such interventions in corporate health management.
Genetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research
2020-06-18

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD.
Structural Correlates of CA2 and CA3 Pyramidal Cell Activity in Freely-Moving Mice
2020-06-18

Plasticity within hippocampal circuits is essential for memory functions. The hippocampal CA2/CA3 region is thought to be able to rapidly store incoming information by plastic modifications of synaptic weights within its recurrent network. High-frequency spike-bursts are believed to be essential for this process, by serving as triggers for synaptic plasticity. Given the diversity of CA2/CA3 pyramidal neurons, it is currently unknown whether and how burst activity, assessed <i>in vivo</i> during natural behavior, relates to principal cell heterogeneity. To explore this issue, we juxtacellularly recorded the activity of single CA2/CA3 neurons from freely-moving male mice, exploring a familiar environment. In line with previous work, we found that spatial and temporal activity patterns of pyramidal neurons correlated with their topographical position. Morphometric analysis revealed that neurons with a higher proportion of distal dendritic length displayed a higher tendency to fire spike-bursts. We propose that the dendritic architecture of pyramidal neurons might determine burst-firing by setting the relative amount of distal excitatory inputs from the entorhinal cortex.<b>SIGNIFICANCE STATEMENT</b> High-frequency spike-bursts are thought to serve fundamental computational roles within neural circuits. Within hippocampal circuits, spike-bursts are believed to serve as potent instructive signals, which increase the efficiency of information transfer and induce rapid modifications of synaptic efficacies. In the present study, by juxtacellularly recording and labeling single CA2/CA3 neurons in freely-moving mice, we explored whether and how burst propensity relates to pyramidal cell heterogeneity. We provide evidence that, within the CA2/CA3 region, neurons with higher proportion of distal dendritic length display a higher tendency to fire spike-bursts. Thus, the relative amount of entorhinal inputs, arriving onto the distal dendrites, might determine the burst propensity of individual CA2/CA3 neurons <i>in vivo</i> during natural behavior.
Cancer surveillance and distress among adult pathogenic TP53 germline variant carriers in Germany: A multicenter feasibility and acceptance survey
2020-06-18

Background Li‐Fraumeni syndrome (LFS) is a high‐risk cancer predisposition syndrome caused by pathogenic germline variants of TP53 . Cancer surveillance has noted a significant survival advantage in individuals with LFS; however, little is known about the feasibility, acceptance, and psychosocial effects of such a program. Methods Pathogenic TP53 germline variant carriers completed a 7‐part questionnaire evaluating sociodemographics, cancer history, surveillance participation, reasons for nonadherence, worries, and distress adapted from the Cancer Worry Scale. Counselees' common concerns and suggestions were assessed in MAXQDA Analytics Pro 12. Results Forty‐nine participants (46 females and 3 males), aged 40.0 ± 12.6 years, formed the study population; 43 (88%) had a personal cancer history (including multiple cancers in 10 [20%]). Forty‐three individuals participated (88%) in surveillance during the study or formerly. Willingness to undergo surveillance was influenced by satisfaction with genetic testing and counseling ( P = .019 [Fisher‐Yates test]) but not by sociodemographics, cancer history, or distress level. Almost one‐third of the participants reported logistical difficulties in implementing surveillance because of the high frequency of medical visits, scheduling difficulties, and the travel distance to their surveillance providers. Self‐reported distress and perceived emotional burden for family members and partners were moderate (median for self‐reported distress, 3.3; median for perceived emotional burden, 3.0). For both, the interquartile range was moderate to very high (2.7‐3.7 and 3.0‐3.7, respectively). Conclusions Individuals with LFS require efficient counseling as well as an accessible, well‐organized, interdisciplinary, standardized surveillance program to increase adherence and psychological coping.
Pandemics' historical role in creating inequality
2020-06-18

In her News Feature "An unequal blow" (15 May, p. 700), L. Wade explores how past pandemics disproportionately affected marginalized groups. It is important to recognize that in addition to exacerbating marginalization, pandemics set the stage for inequalities that have persisted for centuries (1). Historically, pathogens introduced by European conquistadors and colonists contributed to Indigenous population collapses throughout the Americas, facilitating colonial exploitation (2). Abrupt declines in the health and size of Indigenous populations, socio-cultural dislocation, and opportunistic grabs for resources became a strategy used by successive colonial governments (3). As scientists, we have a role in dismantling this colonial playbook to prevent coronavirus disease 2019 (COVID-19) from further marginalizing Indigenous communities.
Pyogenic Liver Abscesses Caused by Acute Appendicitis: Frequency and Diagnostic and Therapeutic Recommendations
2020-06-18

<b><i>Background:</i></b> Pyogenic liver abscesses (PLA) are caused by biliary diseases or hematogenous spreading of mostly intra-abdominal infections. Liver abscesses resulted in hematogenous spreading of infections via the portal vein, such as abscesses caused by acute appendicitis. Pyogenic liver abscesses associated with appendicitis have rarely been described in the literature, especially in adults. The standard therapeutic procedures for liver abscesses are broad-spectrum antibiotic therapy and percutaneous drainage. Surgery for liver abscesses is required in cases of unsuccessful processes. <b><i>Patients and Methods:</i></b> A retrospective analysis of patients with liver abscesses between January 2005 and June 2013 was performed. Parameters investigated included demographics, etiologies of abscesses, treatment modalities, and germ spectrum including antibiotic profile. Five cases of PLA caused by appendicitis were reviewed in detail. <b><i>Results:</i></b> During the study period, 49 patients with PLA and 1,986 patients with acute appendicitis were treated in our hospital. Twenty-one patients with PLA were treated with antibiotic agents and computed tomography (CT)-guided drainage. Liver resections were necessary in 29 of the patients with PLA. In five patients with PLA, abscesses were caused by an acute appendicitis (9.4% of all PLA, 0.25% of all appendicitis operations). Diagnosis of appendicitis as cause of PLA was made during surgery for liver resections in three patients. Previous imaging was not clear in all cases of PLA caused by appendicitis. The most common pre-operative symptoms in patients with PLA caused by appendicitis were fever and right upper quadrant tenderness. <b><i>Discussion:</i></b> Pyogenic liver abscesses caused by acute appendicitis are rare. In the study period of eight and one-half years nearly 2,000 cases of acute appendicitis were treated and five of these patients developed liver abscesses (0.25%). Pyogenic liver abscesses should be considered in patients with unusual high infectious parameters, septic symptoms, and detection of unknown liver lesions.
Genomic Insights into Two Novel Fe(II)-Oxidizing Zetaproteobacteria Isolates Reveal Lifestyle Adaption to Coastal Marine Sediments
2020-06-18

Until recently, the importance and relevance of Zetaproteobacteria were mainly thought to be restricted to high-Fe(II) environments, such as deep-sea hydrothermal vents. The two novel Mariprofundus isolates presented here originate from typical low-Fe(II) coastal marine sediments. As well as being low in Fe(II), these environments are often subjected to fluctuating O 2 concentrations and regular mixing by wave action and bioturbation. The discovery of two novel isolates highlights the importance of these organisms in such environments, as Fe(II) oxidation has been shown to impact nutrients and trace metals. Genome analysis of these two strains further supported their lifestyle adaptation and therefore their potential preference for coastal marine sediments, as genes necessary for surviving dynamic O 2 concentrations and oxidative stress were identified. Furthermore, our analyses also expand our understanding of the poorly understood Fe(II) oxidation pathways used by neutrophilic, microaerophilic Fe(II) oxidizers.
Refining the Multiple Streams Framework’s Integration Concept: Renewable Energy Policy and Ecological Modernization in Germany and Japan in Comparative Perspective
2020-06-18

The article proposes one of the first quantitative operationalizations of the Multiple Streams Framework's (MSF) concept of policy community integration, which determines the gestation process of policy ideas in the policy stream. It argues that operationalization by the Gini coefficient of nodal degree and by Freeman's segregation score enables us to indicate better the type of a policy community (less integrated, or more integrated), and thus, to assume the trajectory of the gestation process. The findings suggest that Policy Network Analysis offers a more progressive operationalization of the integration concept and helps to compare policy communities.
The structure of autocatalytic networks, with application to early biochemistry
2020-06-18

Abstract Metabolism across all known living systems combines two key features. First, all of the molecules that are required are either available in the environment or can be built up from available resources via other reactions within the system. Second, the reactions proceed in a fast and synchronised fashion via catalysts that are also produced within the system. Building on early work by Stuart Kauffman, a precise mathematical model for describing such self-sustaining autocatalytic systems (RAF theory) has been developed to explore the origins and organisation of living systems within a general formal framework. In this paper, we develop this theory further by establishing new relationships between classes of RAFs and related classes of networks, and developing new algorithms to investigate and visualise RAF structures in detail. We illustrate our results by showing how it reveals further details into the structure of archaeal and bacterial metabolism near the origin of life, and provide techniques to study and visualise the core aspects of primitive biochemistry.
The failure of B cells to induce non-canonicalMYD88splice variants correlates with lymphomagenesis via sustained NF-κB signaling
2020-06-18

Abstract Gain-of-function mutations of the TLR adaptor and oncoprotein MyD88 drive B cell lymphomagenesis via sustained NF-κB activation. In myeloid cells, sustained TLR activation and NF-κB activation lead to the induction of inhibitory MYD88 splice variants that restrain prolonged NF-κB activation. We therefore sought to investigate whether such a negative feedback loop exists in B cells. Analyzing MYD88 splice variants in normal B cells and different primary B cell malignancies, we observed that MYD88 splice variants in transformed B cells are dominated by the canonical, strongly NF-κB-activating isoform of MYD88 and contain at least three novel, so far uncharacterized signaling-competent splice isoforms. TLR stimulation in B cells unexpectedly reinforces splicing of NF-κB-promoting, canonical isoforms rather than the ‘MyD88s’, a negative regulatory isoform that is typically induced by TLRs in myeloid cells. This suggests that an essential negative feedback loop restricting TLR signaling in myeloid cells at the level of alternative splicing, is missing in B cells, rendering B cells vulnerable to sustained NF-κB activation and eventual lymphomagenesis. Our results uncover MYD88 alternative splicing as an unappreciated promoter of B cell lymphomagenesis and provide a rationale why oncogenic MYD88 mutations are exclusively found in B cells.
Mechanical Circulatory Support for Cardiovascular Complications in a Young COVID-19 Patient
2020-06-18

The current coronavirus (COVID-19) pandemic is associated with severe pulmonary and cardiovascular complications. This report describes a young patient with COVID-19 without any comorbidity presenting with severe cardiovascular complications, manifesting with pulmonary embolism, embolic stroke, and right heart failure. Management with short-term mechanical circulatory support, including different cannulation strategies, resulted in a successful outcome despite his critical cardiovascular status.
The display makes a difference: A mobile eye tracking study on the perception of art before and after a museum’s rearrangement
2020-06-19

There is increasing awareness that the perception of art is affected by the way it is presented. In 2018, the Austrian Gallery Belvedere redisplayed its permanent collection. Our multi-disciplinary team seized this opportunity to investigate the viewing behavior of specific artworks both before and after the museum’s rearrangement. In contrast to previous mobile eye tracking (MET) studies in museums, this study benefits from the comparison of two realistic display conditions (without any research interference), an unconstrained study design (working with regular museum visitors), and a large data sample (comprising 259 participants). We employed a mixed-method approach that combined mobile eye tracking, subjective mapping (a drawing task in conjunction with an open interview), and a questionnaire in order to relate gaze patterns to processes of meaning-making. Our results show that the new display made a difference in that it 1) generally increased the viewing times of the artworks; 2) clearly extended the reading times of labels; and 3) deepened visitors’ engagement with the artworks in their exhibition reflections. In contrast, interest in specific artworks and art form preferences proved to be robust and independent of presentation modes.
Carotid endarterectomy versus conservative management of the asymptomatic carotid stenosis before coronary artery bypass grafting: a retrospective study
2020-06-19

Abstract Background Our retrospective single-center study aimed to evaluate the safety of the carotid endarterectomy (CEA) in comparison to patients with untreated asymptomatic carotid stenosis ≥60% before CABG. Methods This single-center retrospective study included 174 patients with asymptomatic unilateral carotid stenosis treated between 2004 and 2017 with CABG. Thereof 106 patients had CEA before cardiac surgery either by a simultaneous ( n = 62) or staged ( n = 44) approach. Patients with untreated carotid stenosis served as control (no-CEA group; n = 68). Results The mean stenosis grade was higher in the CEA group (CEA 83% (±1), no-CEA 71% (±1) p &lt; 0.0001). The overall stroke rate was 5/174 (3%) and was due to a high incidence of stroke in the no-CEA group (CEA: 0/106 (0%); No-CEA 5/68 (7%) p = 0.0083). The overall mortality was 1% and comparable between the groups (CEA: 2/106 (2%); No-CEA 0/68 (0%) p = 0.5211). Stroke related mortality was not observed. The groups were similar regarding the incidence of myocardial infarction ( p = 1.0), atrial fibrillation ( p = 0.1931), delirium ( p = 0.2106) and IMC/ICU stay ( p = 0.1542). No significant difference in the subgroup analysis was found between the simultaneous and staged approach regarding the myocardial infarction ( simultaneous : 1/62 (1%); staged: 1/44 (1%); p = 1.0). Conclusions CEA performed as a staged procedure in local anesthesia or a simultaneous procedure in general anesthesia, may reduce the stroke risk prior to CABG.