julilili42/papers huggingface dataset:
Gaze stabilisation behaviour is anisotropic across visual field locations in zebrafish
2019-09-04

Abstract Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs, measured the optokinetic response gain of immobilised zebrafish larvae, and related behaviour to previously published retinal photoreceptor densities. We measured tuning to steradian stimulus size and spatial frequency, and show it to be independent of visual field position. However, zebrafish react most strongly and consistently to lateral, nearly equatorial stimuli, consistent with previously reported higher spatial densities in the central retina of red, green and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance. Author summary The visual system of larval zebrafish mirrors many features present in the visual system of other vertebrates, including its ability to mediate optomotor and optokinetic behaviour. Although the presence of such behaviours and some of the underlying neural correlates have been firmly established, previous experiments did not consider the large visual field of zebrafish, which covers more than 160° for each eye. Given that different parts of the visual field likely carry unequal amount of behaviourally relevant information for the animal, this raises the question whether optic flow is integrated across the entire visual field or just parts of it, and how this shapes behaviour such as the optokinetic response. We constructed a spherical LED arena to present visual stimuli almost anywhere across their visual field, while tracking horizontal eye movements. By displaying moving gratings on this LED arena, we demonstrate that the optokinetic response, one of the most prominent visually induced behaviours of zebrafish, indeed strongly depends on stimulus location and stimulus size, as well as on other parameters such as the spatial and temporal frequency of the gratings. This location dependence is consistent with areas of high retinal photoreceptor densities, though evidence suggests further extraretinal processing.
Recruitment orders underlying binocular coordination of eye position and velocity in the larval zebrafish hindbrain
2019-09-04

Abstract Background The oculomotor integrator (OI) in the vertebrate hindbrain transforms eye velocity input into persistent position coding output, which plays a crucial role in retinal image stability. For a mechanistic understanding of the integrator function and eye position control, knowledge about the tuning of the OI and other oculomotor nuclei is needed. Zebrafish are increasingly used to study integrator function and sensorimotor circuits, yet the precise neuronal tuning to motor variables remains uncharacterized. Results Here, we recorded cellular calcium signals while evoking monocular and binocular optokinetic eye movements at different slow-phase eye velocities. Our analysis reveals the anatomical distributions of motoneurons and internuclear neurons in the nucleus abducens as well as those of oculomotor neurons in caudally adjacent hindbrain volumes. Each neuron is tuned to eye position and/or velocity to variable extents and is only activated after surpassing particular eye position and velocity thresholds. While the abducens (rhombomeres 5/6) mainly codes for eye position, in rhombomeres 7/8 a velocity-to-position coding gradient exists along the rostro-caudal axis, which likely corresponds to the velocity and position storage mechanisms. Position encoding neurons are recruited at eye position thresholds distributed across the behavioral dynamic range, while velocity encoding neurons have more centered firing thresholds for velocity. In the abducens, neurons coding exclusively for one eye intermingle with neurons coding for both eyes. Many of these binocular neurons are preferentially active during conjugate eye movements, which represents a functional diversification in the final common motor pathway. Conclusions We localized and functionally characterized the repertoire of oculomotor neurons in the zebrafish hindbrain. Our findings provide evidence for a mixed but task-specific binocular code and suggest that generation of persistent activity is organized along the rostro-caudal axis in the hindbrain.
Probing Majorana neutrinos with double-β decay
2019-09-05

Looking for an exotic decay Neutrinos—elementary fermionic particles with no electrical charge—defy the standard model of particle physics by having a tiny, but nonzero mass. One explanation for their properties is that they are Majorana fermions, which are particles equal to their antiparticles. If neutrinos were Majorana fermions, a process called neutrinoless double-β decay would become possible: an unstable nucleus could decay by turning two of its neutrons into protons with the emission of two electrons but no antineutrinos. The GERDA Collaboration searched for this decay in a particular isotope of germanium. Housed deep underground to reduce the background signal, the experiment did not detect the elusive process but did place improved boundaries on its half-life. Science , this issue p. 1445
Oxidative stress drives the selection of quorum sensing mutants in the Staphylococcus aureus population
2019-09-05

Significance The QS Agr system of the pathogen S. aureus is a social trait based on bacterial population density that orchestrates the expression of toxins crucial for virulence. Paradoxically, Agr-defective mutants are selected during infection. We studied the selection and fitness of agr mutants under infection-relevant conditions, such as antibiotic stress and hypoxia. Under aerobic growth, the Agr-controlled PSM toxins are produced. These are toxic for Staphylococci and select for agr mutants, which are nonproducers. Contrastingly, hypoxia favors QS maintenance and even allows hyperactivation of the system without imposing a fitness burden. We propose that changing oxygen environments encountered during infection not only alters the virulence potential, but also the course of microbial evolution of the S. aureus community.
Memorability of photographs in subjective cognitive decline and mild cognitive impairment: Implications for cognitive assessment
2019-09-05

Abstract Introduction Impaired long‐term memory is a defining feature of mild cognitive impairment (MCI). We tested whether this impairment is item specific, limited to some memoranda, whereas some remain consistently memorable. Methods We conducted item‐based analyses of long‐term visual recognition memory. Three hundred ninety‐four participants (healthy controls, subjective cognitive decline [SCD], and MCI) in the multicentric DZNE‐Longitudinal Cognitive Impairment and Dementia Study (DELCODE) were tested with images from a pool of 835 photographs. Results We observed consistent memorability for images in healthy controls, SCD, and MCI, predictable by a neural network trained on another healthy sample. Looking at memorability differences between groups, we identified images that could successfully categorize group membership with higher success and a substantial image reduction than the original image set. Discussion Individuals with SCD and MCI show consistent memorability for specific items, while other items show significant diagnosticity. Certain stimulus features could optimize diagnostic assessment, while others could support memory.
1:1 orbital resonance of circumbinary planets
2019-09-05

The recent detection of the third planet in Kepler-47 has shown that binary stars can host several planets in circumbinary orbits. To understand the evolution of these systems we have performed two-dimensional hydrodynamic simulations of the circumbinary disc with two embedded planets for several Kepler systems. In two cases, Kepler-47 and -413, the planets are captured in a 1:1 mean-motion resonance at the planet “parking position” near the inner edge of the disc. The orbits are fully aligned and have mean eccentricities of about 0.25 to 0.30; the planets are entangled in a horseshoe-type motion. Subsequent n-body simulations without the disc show that the configurations are stable. Our results point to the existence of a new class of stable resonant orbits around binary stars. It remains to be seen if such orbits exist in reality.
Acyldepsipeptide Probes Facilitate Specific Detection of Caseinolytic Protease P Independent of Its Oligomeric and Activity State
2019-09-05

Abstract Caseinolytic protease P (ClpP) is a tetradecameric peptidase that assembles with chaperones such as ClpX to gain proteolytic activity. Acyldepsipeptides (ADEPs) are small‐molecule mimics of ClpX that bind into hydrophobic pockets on the apical site of the complex, thereby activating ClpP. Detection of ClpP has so far been facilitated with active‐site‐directed probes which depend on the activity and oligomeric state of the complex. To expand the scope of ClpP labeling, we took a stepwise synthetic approach toward customized ADEP photoprobes. Structure–activity relationship studies with small fragments and ADEP derivatives paired with modeling studies revealed the design principles for suitable probe molecules. The derivatives were tested for activation of ClpP and subsequently applied in labeling studies of the wild‐type peptidase as well as enzymes bearing mutations at the active site and an oligomerization sensor. Satisfyingly, the ADEP photoprobes provided a labeling readout of ClpP independent of its activity and oligomeric state.
Senescence surveillance maintains genomic and functional differentiation in pre-malignant tumors
2019-09-05

Different animal models as well as histological studies using samples from cancer patients clearly showed that cellular senescence is a barrier against tumor progression. Yet, recent data question this concept suggesting that senescent cells may also promote tumor progression. By adopting a senescence-associated secretory phenotype, senescence signaling may even induce dedifferentiation and stemness. To investigate effects of cytokine-induced senescence (CIS) on tumor progression and differentiation, we used pre-malignant u00df-cancers from RIP-Tag2 mice that consecutively express three differentiation antigens: first synaptophysin, then insulin and last glucose transporter-2 (Glut-2). We show that T-helper-cell-mediated immunity prevented the transition of pre-cancerous adenomas into u00df-cancers by stabilizing their genome and u00df-cell functions. Thus, CIS prevented major genomic aberrations, i.e. chromosomal amplifications and losses, by a Stat1- and TNFR1-dependent mechanism. Tumor progression further caused a gradual loss of the functionally relevant differentiation markers insulin and Glut-2. CIS prevented this loss in vivo, again in a strictly cytokine signaling-dependent manner, and preserved the physiological islet functions of the pre-malignant cells ex vivo. Additional experiments revealed that treatment of isolated u00df-cancer cells with interferon-gamma and tumor necrosis factor retained the expression of u00df-cell differentiation markers also in vitro. Taken together, immunity-induced senescence surveillance protects against dedifferentiation of endocrine u00df-cancers thereby enabling the diseased mice to control glucose homeostasis.
Polygenic burden in focal and generalized epilepsies
2019-09-06

Abstract Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10−15; Cleveland: P = 2.85×10−4; Finnish-ancestry Epi25: P = 1.80×10−4) or population controls (Epi25: P = 2.35×10−70; Cleveland: P = 1.43×10−7; Finnish-ancestry Epi25: P = 3.11×10−4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10−4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10−19; Cleveland: P = 1.69×10−6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10−15; Cleveland: P = 1.39×10−2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls—in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.
World’s fastest brain-computer interface: Combining EEG2Code with deep learning
2019-09-06

We present a novel approach based on deep learning for decoding sensory information from non-invasively recorded Electroencephalograms (EEG). It can either be used in a passive Brain-Computer Interface (BCI) to predict properties of a visual stimulus the person is viewing, or it can be used to actively control a BCI application. Both scenarios were tested, whereby an average information transfer rate (ITR) of 701 bit/min was achieved for the passive BCI approach with the best subject achieving an online ITR of 1237 bit/min. Further, it allowed the discrimination of 500,000 different visual stimuli based on only 2 seconds of EEG data with an accuracy of up to 100%. When using the method for an asynchronous self-paced BCI for spelling, an average utility rate of 175 bit/min was achieved, which corresponds to an average of 35 error-free letters per minute. As the presented method extracts more than three times more information than the previously fastest approach, we suggest that EEG signals carry more information than generally assumed. Finally, we observed a ceiling effect such that information content in the EEG exceeds that required for BCI control, and therefore we discuss if BCI research has reached a point where the performance of non-invasive visual BCI control cannot be substantially improved anymore.
Critical Behavior of the Quantum Contact Process in One Dimension
2019-09-06

The contact process is a paradigmatic classical stochastic system displaying critical behavior even in one dimension. It features a nonequilibrium phase transition into an absorbing state that has been widely investigated and shown to belong to the directed percolation universality class. When the same process is considered in a quantum setting, much less is known. So far, mainly semiclassical studies have been conducted and the nature of the transition in low dimensions is still a matter of debate. Also, from a numerical point of view, from which the system may look fairly simple-especially in one dimension-results are lacking. In particular, the presence of the absorbing state poses a substantial challenge, which appears to affect the reliability of algorithms targeting directly the steady state. Here we perform real-time numerical simulations of the open dynamics of the quantum contact process and shed light on the existence and on the nature of an absorbing state phase transition in one dimension. We find evidence for the transition being continuous and provide first estimates for the critical exponents. Beyond the conceptual interest, the simplicity of the quantum contact process makes it an ideal benchmark problem for scrutinizing numerical methods for open quantum nonequilibrium systems.
Quantification of Motor Function in Huntington Disease Patients Using Wearable Sensor Devices
2019-09-06

Previous studies have demonstrated the feasibility and promise of wearable sensors as objective measures of motor impairment in Parkinson disease and essential tremor. However, there are few published studies that have examined such an application in Huntington disease (HD). This report provides an evaluation of the potential to objectively quantify chorea in HD patients using wearable sensor data. Data were derived from a substudy of the phase 2 Open-PRIDE-HD study, where 17 patients were screened and 15 patients enrolled in the substudy and ultimately 10 patients provided sufficient wearable sensor data. The substudy was designed to provide high-resolution data to inform design of predictive algorithms for chorea quantification. During the entire course of the 6-month study, in addition to chorea ratings from 18 in-clinic assessments, 890 home assessments, and 1,388 responses to daily reminders, 33,000 h of high-resolution accelerometer data were captured continuously from wearable smartwatches and smartphones. Despite its limited sample size, our study demonstrates that arm chorea can be characterized using accelerometer data during static assessments. Nonetheless, the small sample size limits the generalizability of the model. The sensor-based model can quantify the chorea level with high correlation to the chorea severity reported by both clinicians and patients. In addition, our analysis shows that the chorea digital signature varies between patients. This work suggests that digital wearable sensors have the potential to support clinical development of medications in patients with movement disorders, such as chorea. However, additional data would be needed from a larger number of HD patients with a full range of chorea severity (none to severe) with and without intervention to validate this potentially predictive technology.
Multi-wavelength variability of the young solar analog ι Horologii
2019-09-06

Context. Chromospheric activity cycles are common in late-type stars; however, only a handful of coronal activity cycles have been discovered. ι Hor is the most active and youngest star with known coronal cycles. It is also a young solar analog, and we are likely facing the earliest cycles in the evolution of solar-like stars, at an age (~600 Myr) when life appeared on Earth. Aims. Our aim is to confirm the ~1.6 yr coronal cycle and characterize its stability over time. We use X-ray observations of ι Hor to study the corona of a star representing the solar past through variability, thermal structure, and coronal abundances. Methods. We analyzed multi-wavelength observations of ι Hor using XMM-Newton , TESS, and HST data. We monitored ι Hor throughout almost seven years in X-rays and in two UV bands. The summed RGS and STIS spectra were used for a detailed thermal structure model, and the determination of coronal abundances. We studied rotation and flares in the TESS light curve. Results. We find a stable coronal cycle along four complete periods, more than covered in the Sun. There is no evidence for a second longer X-ray cycle. Coronal abundances are consistent with photospheric values, discarding any effects related to the first ionization potential. From the TESS light curve we derived the first photometric measurement of the rotation period (8.2 d). No flares were detected in the TESS light curve of ι Hor. We estimate the probability of having detected zero flares with TESS to be ~2%. Conclusions. We corroborate the presence of an activity cycle of ~1.6 yr in ι Hor in X-rays, more regular than its Ca II H&amp;K counterpart. A decoupling of the activity between the northern and southern hemispheres of the star might explain the disagreement. The inclination of the system would result in an irregular behavior in the chromospheric indicators. The more extended coronal material would be less sensitive to this effect.
Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS)—pilot evaluation of a simple point-of-care ultrasound protocol and short training program for detecting urinary tract morbidity in highly endemic settings
2019-09-06

Abstract Background Urogenital schistosomiasis (UGS) causes inflammation and fibrosis of the urinary tract. In resource-limited settings, affordable tools for morbidity assessment in clinical care are needed. Point-of-care ultrasound has not yet been validated for UGS-related pathology. Methods We developed a protocol for Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS), assessing pathology of the bladder wall, ureters and kidneys. Following standardized training, two clinicians performed FASUS on children and adults with hematuria in Lambaréné, Gabon. Recorded ultrasound clips were remotely reviewed by two ultrasound experts as a diagnostic reference. Results In 2015 and 2016, scans were performed in 118 patients. The image quality was sufficient in 90% of bladder views and more than 97% of kidney views. UGS-compatible pathology was detected in 51/118 (43%) by the operator and in 46/107 (43%) by the experts among baseline scans of sufficient quality. Inter-rater agreement between operators and experts was very good (κ &gt; 0.8) for hydronephrosis and good (κ &gt; 0.6) for bladder wall thickening. Conclusions FASUS is a promising clinical, point-of-care tool for detecting UGS-related urinary tract morbidity in symptomatic patients. Based on larger validation studies, appropriate diagnostic and therapeutic algorithms for the use of FASUS should be established.
Lipid Atlas of Keratinocytes and Betulin Effects on its Lipidome Profiled by Comprehensive UHPLC–MS/MS with Data Independent Acquisition Using Targeted Data Processing
2019-09-06

Abstract Betulin is a pentacyclic triterpene with demonstrated healing properties in mid‐dermal wounds. A few earlier studies have provided insights into the wound healing effects on the molecular level. However, there are still questions left on the molecular targets of betulin. Therefore, a pharmacolipidomics analysis of betulin is undertaken in human immortalized keratinocytes to monitor alterations in the lipid profiles induced by treatment with betulin. For this purpose, lipid extracts of keratinocytes treated with betulin and untreated controls are comprehensively analyzed by an untargeted UHPLC–ESI–QTOF‐MS/MS lipidomics profiling workflow using data‐independent acquisition. Targeted data processing allows the identification of 611 lipid species from 21 different lipid classes. Statistical analysis of the identified lipids shows significant changes in 440 lipid species that can be described as downregulation of cholesteryl esters and triacylglycerides and upregulation of glycerophospholipids, sphingolipids, and diacylglycerides. Additionally, some other signals corresponding to triterpenes are found in the betulin group and suggested that betulin is incorporated (in the membrane) and metabolized in keratinocytes.