julilili42/papers huggingface dataset:
Targeting intracellular signaling as an antiviral strategy: aerosolized LASAG for the treatment of influenza in hospitalized patients
2018-03-05

Influenza has been a long-running health problem and novel antiviral drugs are urgently needed. In pre-clinical studies, we demonstrated broad antiviral activity of D, L-lysine-acetylsalicylate glycine (LASAG) against influenza virus (IV) in cell culture and protection against lethal challenge in mice. LASAG is a compound with a new antiviral mode of action. It inhibits the NF-κB signal transduction module that is essential for IV replication. Our goal was to determine whether aerosolized LASAG would also show a therapeutic benefit in hospitalized patients suffering from severe influenza. The primary endpoint was time to alleviation of clinical influenza symptoms. The primary analysis was based on the modified intention-to-treat (MITT) population. This included all patients with confirmed influenza virus infection who received at least one treatment. The per protocol (PP) analysis set included all subjects from the MITT population who underwent at least 13 inhalations. In the MITT group, 48 (41.7%) participants (29 LASAG; 19 placebo) had severe influenza. The mean time to symptom alleviation was 56.2 h in the placebo group and 43.0 h in the LASAG group. The PP set consisted of 41 patients (24 LASAG; 17 placebo). The mean time to symptom alleviation in the LASAG group (38.3 h; P = 0.0365) was lower than that in the placebo group (56.2 h). In conclusion, LASAG improved the time to alleviation of influenza symptoms in hospitalized patients. The present phase II proof-of-concept (PoC) study demonstrates that targeting an intra-cellular signaling pathway using aerosolized LASAG improves the time to symptom alleviation compared to standard treatment.
Costs and benefits of admixture between foreign genotypes and local populations in the field
2018-03-05

Abstract Admixture is the hybridization between populations within one species. It can increase plant fitness and population viability by alleviating inbreeding depression and increasing genetic diversity. However, populations are often adapted to their local environments and admixture with distant populations could break down local adaptation by diluting the locally adapted genomes. Thus, admixed genotypes might be selected against and be outcompeted by locally adapted genotypes in the local environments. To investigate the costs and benefits of admixture, we compared the performance of admixed and within‐population F1 and F2 generations of the European plant Lythrum salicaria in a reciprocal transplant experiment at three European field sites over a 2‐year period. Despite strong differences between site and plant populations for most of the measured traits, including herbivory, we found limited evidence for local adaptation. The effects of admixture depended on experimental site and plant population, and were positive for some traits. Plant growth and fruit production of some populations increased in admixed offspring and this was strongest with larger parental distances. These effects were only detected in two of our three sites. Our results show that, in the absence of local adaptation, admixture may boost plant performance, and that this is particularly apparent in stressful environments. We suggest that admixture between foreign and local genotypes can potentially be considered in nature conservation to restore populations and/or increase population viability, especially in small inbred or maladapted populations.
Oxic Fe(III) reduction could have generated Fe(II) in the photic zone of Precambrian seawater
2018-03-05

Abstract Many marine Precambrian iron formations (IF) record deep anoxic seawater enriched in Fe(II) (i.e. ferruginous) overlain by mildly oxygenated surface water. This is reflected by iron-rich sediments forming in deep basins, and relatively iron-poor sediments forming in shallow, sunlit waters. Such an iron gradient is often interpreted as a redox interface where dissolved Fe(II) was oxidized and precipitated as Fe(III)-bearing minerals. As such, sedimentary iron enrichments are proxy to the progressive oxidation of the oceans through geological time. However, this interpretation is founded on the assumption that Fe(II) could not persist within an oxygenated water column. Here, we cultivated cyanobacteria in an illuminated column supplied with Fe(II)-rich seawater medium in a laboratory-scale analog of a continental margin supporting IF deposition. We first observed Fe(II) oxidation with oxygen, then biologically-mediated reduction of Fe(III) (oxyhydr)oxides, which maintained a pool of Fe(II) in the presence of oxygen. Such steady-state iron redox cycling may have maintained dissolved, and hence mobile Fe(II) in oxygenated seawater above ferruginous deep basins such as those inferred for many Precambrian IF.
Safety of intranasal human insulin: A review
2018-03-06

Aims To conduct a review in order to assess the safety of intranasal human insulin in clinical studies as well as the temporal stability of nasal insulin sprays. Material and methods An electronic search was performed using MEDLINE. We selected original research on intranasal human insulin without further additives in humans. The studies included could be of any design as long as they used human intranasal insulin as their study product. All outcomes and adverse side effects were extracted. Results A total of 38 studies in 1092 individuals receiving acute human intranasal insulin treatment and 18 studies in 832 individuals receiving human intranasal insulin treatment lasting between 21 days and 9.7 years were identified. No cases of symptomatic hypoglycaemia or severe adverse events (AEs) were reported. Transient local side effects in the nasal area were frequently experienced after intranasal insulin and placebo spray, while other AEs were less commonly reported. There were no reports of participants being excluded as a result of AEs. No instances of temporal stability of nasal insulin were reported in the literature. Tests on insulin that had been repacked into spray flasks showed that it had a chemical stability of up to 57 days. Conclusions Our retrospective review of published studies on intranasal insulin did not reveal any safety concerns; however, there were insufficient data to ensure the long‐term safety of this method of chronic insulin administration. Improved insulin preparations that cause less nasal irritation would be desirable for future treatment.
Amniotic Membrane Transplantation in Reconstructive and Regenerative Ophthalmology
2018-03-06

BACKGROUND The goal of this study was to investigate numbers, indications, surgical techniques, and experiences of amniotic membrane transplantation at the University Eye Hospital Tübingen over the last 16 years. MATERIAL AND METHODS Data from all amniotic membrane transplantations from January 2001 to December 2016 were retrospectively analyzed. Data was accessed from the electronic database and the annual reports of the Eye Bank at the University Eye Hospital Tübingen. RESULTS A total of 771 amniotic membrane transplantations were performed between 2001 and 2016 at the University Eye Hospital Tübingen. The mean number of amniotic membrane transplantations was 48 per year (range: 7-81). Overall, the mean number of amniotic membrane transplantations more than doubled, from 31 amniotic membrane transplantations per year during the first 8-year period to 66 amniotic membrane transplantations per year during the second 8-year period (p<0.0001). The most common surgical indications for amniotic membrane transplantation were corneal ulcers and persistent corneal epithelial defects. The inlay, overlay, and sandwich technique became the favored surgical methods for various disorders of the ocular surface. CONCLUSIONS Our study showed a significant increase of amniotic membrane transplantations from 2001 to 2016. This increase is likely influenced by the introduction of different surgical amniotic membrane transplantation techniques, the rising knowledge about containing growth factors, neurotrophins and cytokines, and the demographic change with aging of the population.
Label-free high-speed wide-field imaging of single microtubules using interference reflection microscopy
2018-03-06

Summary When studying microtubules in vitro, label free imaging of single microtubules is necessary when the quantity of purified tubulin is too low for efficient fluorescent labeling or there is concern that labelling will disrupt its function. Commonly used techniques for observing unlabeled microtubules, such as video enhanced differential interference contrast, dark-field and more recently laser-based interferometric scattering microscopy, suffer from a number of drawbacks. The contrast of differential interference contrast images depends on the orientation of the microtubules, dark-field is highly sensitive to impurities and optical misalignments, and interferometric scattering has a limited field of view. In addition, all of these techniques require costly optical components such as Nomarski prisms, dark-field condensers, lasers and laser scanners. Here we show that single microtubules can be imaged at high speed and with high contrast using interference reflection microscopy without the aforementioned drawbacks. Interference reflection microscopy is simple to implement, requiring only the incorporation of a 50/50 mirror instead of a dichroic in a fluorescence microscope, and with appropriate microscope settings has similar signal-to-noise ratio to differential interference contrast and fluorescence. We demonstrated the utility of interference reflection microscopy by high speed imaging and tracking of dynamic microtubules at 100 frames per second. In conclusion, the image quality of interference reflection microscopy is similar to or exceeds that of all other techniques and, with minimal microscope modification, can be used to study the dynamics of unlabeled microtubules.
Preparation and purification of organic samples for selenium isotope studies
2018-03-06

Selenium (Se) is an important micronutrient but also a strong toxin with a narrow tolerance range for many organisms. As such, a globally heterogeneous Se distribution in soils is responsible for various disease patterns (i.e. Se excess and deficiency) and environmental problems, whereby plants play a key role for the Se entrance into the biosphere. Selenium isotope variations were proved to be a powerful tracer for redox processes and are therefore promising for the exploration of the species dependent Se metabolism in plants and the Se cycling within the Critical Zone. Plant cultivation setups enable systematic controlled investigations, but samples derived from them–plant tissue and phytoagar–are particularly challenging and require specific preparation and purification steps to ensure precise and valid Se isotope analytics performed with HG-MC-ICP-MS. In this study, different methods for the entire process from solid tissue preparation to Se isotope measurements were tested, optimized and validated. A particular microwave digestion procedure for plant tissue and a vacuum filtration method for phytoagar led to full Se recoveries, whereby unfavorable organic residues were reduced to a minimum. Three purification methods predominantly described in the literature were systematically tested with pure Se solution, high concentrated multi-element standard solution as well as plant and phytoagar as target matrices. All these methods efficiently remove critical matrix elements, but differ in Se recovery and organic residues. Validation tests doping Se-free plant material and phytoagar with a reference material of known Se isotope composition revealed the high impact of organic residues on the accuracy of MC-ICP-MS measurements. Only the purification method with no detectable organic residues, hydride generation and trapping, results in valid mass bias correction for plant samples with an average deviation to true δ82/76Se values of 0.2 ‰ and a reproducibility (2 SD) of ± 0.2 ‰. For phytoagar this test yields a higher deviation of 1.1 ‰ from the true value and a 2 SD of ± 0.1 ‰. The application of the developed methods to cultivated plants shows sufficient accuracy and precision and is a promising approach to resolve plant internal Se isotope fractionations, for which respective δ82/76Se values of +2.3 to +3.5 ‰ for selenate and +1.2 to +1.9 ‰ for selenite were obtained.
Oxytocin and Eating Disorders: A Narrative Review on Emerging Findings and Perspectives
2018-03-07

We propose a framework of oxytocin's role and its therapeutic potential in eating disorders that aims at integrating social and metabolic aspects of its pharmacological profile, and ponder perspectives and limitations of oxytocin use in the clinical setting.
Generation of iPSCs carrying a common LRRK2 risk allele for in vitro modeling of idiopathic Parkinson's disease
2018-03-07

Induced pluripotent stem cells (iPSCs) have recapitulated several aspects of Parkinson's disease (PD), but most iPSCs are derived from familial cases, which account for only about 15% of patients. Thus, while the emphasis has justifiably been on using iPSCs to model rare familial cases, models for the most common forms of PD are critically lacking. Here, we report the generation of an iPSC-based model of idiopathic PD (iPD) with or without RS1491923, which is a common risk variant in the LRRK2 locus. Consistent with GWA studies, we found large variability in our datasets. However, iPSC-derived neurons carrying the risk allele emerged for displaying subtle disturbances of cellular degradative systems, in line with familial PD models. We also observed that treatment with the LRRK2 inhibitor CZC-25146 slightly reduced a marker of aSYN pathology in all iPD lines. Future iPSC-based studies may need to be structured similarly to large GWA studies in order to obtain relevant statistical power. However, results from this pilot study suggest that iPSC-based modeling represents an attractive way to investigate idiopathic diseases.
CNS progression during vinblastine or targeted therapies for high‐risk relapsed ALK‐positive anaplastic large cell lymphoma: A case series
2018-03-07

Abstract Vinblastine and targeted therapies induce remissions in patients with relapsed or progressive anaplastic lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALCL). Central nervous system (CNS) prophylaxis often is not included during re‐induction in CNS‐negative relapse patients. We report on five patients with progressive or early relapsed ALK‐positive ALCL who developed CNS progression during re‐induction with vinblastine, crizotinib, or brentuximab vedotin given for bridging to allogeneic blood stem cell transplantation. These observations suggest that CNS prophylaxis should be considered in ALCL patients suffering progression during initial therapy who receive re‐induction using agents with limited CNS penetration.
Generation of Annelated Dicarbenes and Their Alkali-Metal Chelate Complexes in Solution: Equilibrium between Hetero- and Homoleptic NHC Lithium Complexes
2018-03-07

Attempts to generate the free bis(N-heterocyclic carbene) vegiR (R = nPr, tBu; vegiR = 2,7-dihydro-2,7-dialkyldiimidazo[1,5-b:5′,1′-f]pyridazine-1,8-diylidene) from its imidazolium salts 1 with alkali-metal bases resulted exclusively in the formation of the respective lithium, sodium, and potassium complexes 2–4 due to the strongly chelating properties of the dicarbene. DFT calculations reveal pronounced dispersion interactions in the case of N-tert-butyl substituents as the reason for the formation of the homoleptic lithium species 2b-H in solution. The dynamic behavior of the lithium complexes in equilibrium was studied by NMR techniques. Attempts to liberate the free carbenes by addition of the respective crown ethers failed for the lithium and sodium complexes. Deprotonation of the imidazolium salts 1a,b with the strong metal-free phosphazene base P4-tBu ({(Me2N)3PN}3PNtBu) generated successfully the free dicarbenes vegiR (5) and monocarbene 6b in solution.
Home Dental Bleaching Monitored With Microelectronic Sensors to Record the Wearing Times of an Acetate Tray/Bleaching Product
2018-03-07

SUMMARY The present case study quantifies the clinical wearing time of an acetate tray/bleaching product during home dental bleaching. The patient was instructed to use a 10% carbamide peroxide gel for 6-8 hours each day for 20 days. The wearing time of the tray was measured by a microsensor from TheraMon microelectronic system (Sales Agency Gschladt, Hargelsberg, Austria) completely embedded in the tray so that the clinician would be informed as to the precise time the tray was placed in the mouth. Evaluation of the daily printout during dental bleaching demonstrated that the patient did not correctly follow the clinician's instructions as to the wearing time of the tray. Recording the wearing time of dental bleaching agents can be beneficial for both dental professional and patient to obtain a more effective treatment according to the patient's needs and expectations.
Draft Genome Sequence and Annotation of the Phytopathogenic Ralstonia pickettii (Previously Burkholderia glumae) Strain ICMP-8657
2018-03-07

ABSTRACT Strain ICMP-8657 was formerly taxonomically classified as Burkholderia glumae and reported to be the producer of an antibacterial pyrazole derivative. Here, we report the draft genome sequence of ICMP-8657, which failed to demonstrate the biosynthetic capacity to produce the stated antibacterial compound, leading to its taxonomic reclassification as Ralstonia pickettii ICMP-8657.
Layer 3 dynamically coordinates columnar activity according to spatial context
2018-03-07

Abstract Spatial integration is a fundamental, context-dependent neural operation that involves extensive neural circuits across cortical layers of V1. To better understand how spatial integration is dynamically coordinated across layers we recorded single- and multi-unit activity and local field potentials across V1 layers of awake mice, and used dynamic Bayesian model comparisons to identify when laminar activity and inter-laminar functional interactions showed surround suppression, the hallmark of spatial integration. We found that surround suppression is strongest in layer 3 (L3) and L4 activity, showing rapidly sharpening receptive fields and increasing suppression strength. Importantly, we also found that specific directed functional connections were strongest for intermediate stimulus sizes and suppressed for larger ones, particularly for the L3-&gt;L5 and L3-&gt;L1 connections. Taken together, the results shed light on the different functional roles of cortical layers in spatial integration and show how L3 dynamically coordinates activity across a cortical column depending on spatial context.
LED-based interference-reflection microscopy combined with optical tweezers for quantitative three-dimensional single microtubule imaging
2018-03-07

Abstract Optical tweezers combined with various microscopy techniques are a versatile tool for single-molecule force spectroscopy. However, some combinations may compromise measurements. Here, we combined optical tweezers with total-internal-reflection-fluorescence (TIRF) and interference-reflection microscopy (IRM). Using a light-emitting diode (LED) for IRM illumination, we show that single microtubules can be resolved with high contrast. Furthermore, we converted the IRM interference pattern of an upward bent microtubule to its three-dimensional (3D) profile calibrated against the optical tweezers and evanescent TIRF field. In general, LED-based IRM is a powerful method for high-resolution 3D microscopy. OCIS codes (180.3170) Interference microscopy; (120.4570) Optical design of instruments (350.4855); Optical tweezers or optical manipulation.
Addressing the contribution of climate and vegetation cover on hillslope denudation, Chilean Coastal Cordillera (26°–38°S)
2018-03-08

The Earth surface is modulated by interactions among tectonics, climate, and biota. The influence of each of these factors on hillslope denudation rates is difficult to disentangle. The Chilean Coastal Cordillera offers a strong climate and vegetation gradient from arid and unvegetated in the North to humid and vegetated in the South. A similar (convergent) plate tectonic boundary lies to the West of the Coastal Cordillera. We present eight depth profiles analyzed for in situ-produced cosmogenic Be-10 in four study areas. These profiles reveal denudation rates of soil-mantled hillslopes and the depth of mobile layers. Depth profiles were investigated from both S- and N-facing mid-slope positions. Results indicate the depth of the mobile layers in the four study areas increase from N to S in latitude. When mixing is present in the mobile layers they are completely mixed. In the S- and N-facing hillslopes of each study area, mid-slope positions do not show a systematic change in depth of the mobile layers nor in denudation rates based on cosmogenic depth profiles. From N to S in latitude, modelled denudation rates of hillslopes increase from similar to 0.46 to similar to 5.65 cm/kyr and then decrease to similar to 3.22 cm/kyr in the southernmost, highest vegetation cover, study area. Calculated turnover times of soils decrease from 30 to similar to 11 kyr and then increase to similar to 22 kyr. In this work, the increasing denudation rates are attributed to increasing mean annual precipitation from N to S. However, despite the ongoing increase in precipitation from N to S, the denudation rate in the southernmost location does not continue to increase due to the protective nature of increasing vegetation cover. This indicates a vegetation induced non-linear relationship with denudation rates. (C) 2018 Elsevier B.V. All rights reserved.
Human V4 Activity Patterns Predict Behavioral Performance in Imagery of Object Color
2018-03-08

Color is special among basic visual features in that it can form a defining part of objects that are engrained in our memory. Whereas most neuroimaging research on human color vision has focused on responses related to external stimulation, the present study investigated how sensory-driven color vision is linked to subjective color perception induced by object imagery. We recorded fMRI activity in male and female volunteers during viewing of abstract color stimuli that were red, green, or yellow in half of the runs. In the other half we asked them to produce mental images of colored, meaningful objects (such as tomato, grapes, banana) corresponding to the same three color categories. Although physically presented color could be decoded from all retinotopically mapped visual areas, only hV4 allowed predicting colors of imagined objects when classifiers were trained on responses to physical colors. Importantly, only neural signal in hV4 was predictive of behavioral performance in the color judgment task on a trial-by-trial basis. The commonality between neural representations of sensory-driven and imagined object color and the behavioral link to neural representations in hV4 identifies area hV4 as a perceptual hub linking externally triggered color vision with color in self-generated object imagery. SIGNIFICANCE STATEMENT Humans experience color not only when visually exploring the outside world, but also in the absence of visual input, for example when remembering, dreaming, and during imagery. It is not known where neural codes for sensory-driven and internally generated hue converge. In the current study we evoked matching subjective color percepts, one driven by physically presented color stimuli, the other by internally generated color imagery. This allowed us to identify area hV4 as the only site where neural codes of corresponding subjective color perception converged regardless of its origin. Color codes in hV4 also predicted behavioral performance in an imagery task, suggesting it forms a perceptual hub for color perception.