julilili42/papers huggingface dataset:
Overcoming the divide between ataxias and spastic paraplegias: Shared phenotypes, genes, and pathways
2017-02-14

ABSTRACT Autosomal‐dominant spinocerebellar ataxias, autosomal‐recessive spinocerebellar ataxias, and hereditary spastic paraplegias have traditionally been designated in separate clinicogenetic disease classifications. This classification system still largely frames clinical thinking and genetic workup in clinical practice. Yet, with the advent of next‐generation sequencing, phenotypically unbiased studies have revealed the limitations of this classification system. Various genes (eg, SPG7, SYNE1, PNPLA6 ) traditionally rooted in either the ataxia or hereditary spastic paraplegia classification system have now been shown to cause ataxia on the one end of the disease continuum and hereditary spastic paraplegia on the other. Other genes such as GBA2 and KIF1C were almost simultaneously published as both a hereditary spastic paraplegia and an ataxia gene. The variability and fluidity of observed phenotypes along the ataxia‐spasticity spectrum warrants a rethinking of the traditional classification system. We propose to replace this divisive diagnosis‐driven ataxia and hereditary spastic paraplegia classification system by a descriptive, unbiased approach of modular phenotyping . This approach is also open to expansion of the phenotype beyond ataxia and spasticity, which often occur as part of broader multisystem neuronal dysfunction. The concept of a continuous ataxia‐spasticity disease spectrum is further supported by ataxias and hereditary spastic paraplegias sharing not only overlapping phenotypes and underlying genes, but also common cellular pathways and disease mechanisms. This suggests a shared vulnerability of cerebellar and corticospinal neurons for common pathophysiological processes. It might be this mechanistic overlap that drives their clinical overlap. A mechanistically inspired classification system will help to pave the way for mechanism‐based strategies for drug development. © 2017 International Parkinson and Movement Disorder Society
Anomalously old biotite40Ar/39Ar ages in the NW Himalaya
2017-02-14

Biotite &lt;sup&gt;40&lt;/sup&gt;Ar/&lt;sup&gt;39&lt;/sup&gt;Ar ages older than corresponding muscovite &lt;sup&gt;40&lt;/sup&gt;Ar/&lt;sup&gt;39&lt;/sup&gt;Ar ages, contrary to the diffusion properties of these minerals, are common in the Himalaya and other metamorphic regions. In these cases, biotite &lt;sup&gt;40&lt;/sup&gt;Ar/&lt;sup&gt;39&lt;/sup&gt;Ar ages are commonly dismissed as “too old” on account of “excess Ar.” We present 32 step-heating &lt;sup&gt;40&lt;/sup&gt;Ar/&lt;sup&gt;39&lt;/sup&gt;Ar ages from 17 samples from central Himachal Pradesh Himalaya, India. In almost all cases, the biotite ages are older than predicted from cooling histories. We document host-rock lithology and chemical composition, mica microstructures, biotite chemical composition, and chlorite and muscovite components of biotite separates to demonstrate that these factors do not offer an explanation for the anomalously old biotite &lt;sup&gt;40&lt;/sup&gt;Ar/&lt;sup&gt;39&lt;/sup&gt;Ar ages. We discuss possible mechanisms that may account for extraneous Ar (inherited or excess Ar) in these samples. The most likely cause for “too-old” biotite is excess Ar, i.e., &lt;sup&gt;40&lt;/sup&gt;Ar that is separated from its parent K. We suggest that this contamination resulted from one or several of the following mechanisms: (1) &lt;sup&gt;40&lt;/sup&gt;Ar was released during Cenozoic prograde metamorphism; (2) &lt;sup&gt;40&lt;/sup&gt;Ar transport was restricted due to a temporarily dry intergranular medium; (3) &lt;sup&gt;40&lt;/sup&gt;Ar was released from melt into a hydrous fluid phase during melt crystallization. Samples from the Main Central Thrust shear zone may be affected by a different mechanism of excess-Ar accumulation, possibly linked to later-stage fluid circulation within the shear zone and chloritization. Different Ar diffusivities and/or solubilities in biotite and muscovite may explain why biotite is more commonly affected by excess Ar than muscovite.
Nitrate capture and slow release in biochar amended compost and soil
2017-02-15

Slow release of nitrate by charred organic matter used as a soil amendment (i.e. biochar) was recently suggested as potential mechanism of nutrient delivery to plants which may explain some agronomic benefits of biochar. So far, isolated soil-aged and composted biochar particles were shown to release considerable amounts of nitrate only in extended (>1 h) extractions ("slow release"). In this study, we quantified nitrate and ammonium release by biochar-amended soil and compost during up to 167 h of repeated extractions in up to six consecutive steps to determine the effect of biochar on the overall mineral nitrogen retention. We used composts produced from mixed manures amended with three contrasting biochars prior to aerobic composting and a loamy soil that was amended with biochar three years prior to analysis and compared both to non-biochar amended controls. Composts were extracted with 2 M KCl at 22°C and 65°C, after sterilization, after treatment with H2O2, after removing biochar particles or without any modification. Soils were extracted with 2 M KCl at 22°C. Ammonium was continuously released during the extractions, independent of biochar amendment and is probably the result of abiotic ammonification. For the pure compost, nitrate extraction was complete after 1 h, while from biochar-amended composts, up to 30% of total nitrate extracted was only released during subsequent extraction steps. The loamy soil released 70% of its total nitrate amount in subsequent extractions, the biochar-amended soil 58%. However, biochar amendment doubled the amount of total extractable nitrate. Thus, biochar nitrate capture can be a relevant contribution to the overall nitrate retention in agroecosystems. Our results also indicate that the total nitrate amount in biochar amended soils and composts may frequently be underestimated. Furthermore, biochars could prevent nitrate loss from agroecosystems and may be developed into slow-release fertilizers to reduce global N fertilizer demands.
Chasing discs around O-type (proto)stars: Evidence from ALMA observations
2017-02-15

Context. Circumstellar discs around massive stars could mediate the accretion onto the star from the infalling envelope, and could minimize the effects of radiation pressure. Despite such a crucial role, only a few convincing candidates have been provided for discs around deeply embedded O-type (proto)stars. Aims: In order to establish whether disc-mediated accretion is the formation mechanism for the most massive stars, we have searched for circumstellar, rotating discs around a limited sample of six luminous (&gt;105L⊙) young stellar objects. These objects were selected on the basis of their IR and radio properties in order to maximize the likelihood of association with disc+jet systems. Methods: We used ALMA with 0.̋2 resolution to observe a large number of molecular lines typical of hot molecular cores. In this paper we limit our analysis to two disc tracers (methyl cyanide, CH3CN, and its isotopologue, 13CH3CN), and an outflow tracer (silicon monoxide, SiO). Results: We reveal many cores, although their number depends dramatically on the target. We focus on the cores that present prominent molecular line emission. In six of these a velocity gradient is seen across the core,three of which show evidence of Keplerian-like rotation. The SiO data reveal clear but poorly collimated bipolar outflow signatures towards two objects only. This can be explained if real jets are rare (perhaps short-lived) in very massive objects and/or if stellar multiplicity significantly affects the outflow structure.For all cores with velocity gradients, the velocity field is analysed through position-velocity plots to establish whether the gas is undergoing rotation with νrot ∝ R- α, as expected for Keplerian-like discs. Conclusions: Our results suggest that in three objects we are observing rotation in circumstellar discs, with three more tentative cases, and one core where no evidence for rotation is found. In all cases but one, we find that the gas mass is less than the mass of any embedded O-type star, consistent with the (putative) discs undergoing Keplerian-like rotation. With the caveat of low number statistics, we conclude that the disc detection rate could be sensitive to the evolutionary stage of the young stellar object. In young, deeply embedded sources, the evidence for discs could be weak because of confusion with the surrounding envelope, while in the most evolved sources the molecular component of the disc could have already been dispersed. Only in those objects that are at an intermediate stage of the evolution would the molecular disc be sufficiently prominent and relatively less embedded to be detectable by mm/submm observations.
Renal cystic disease and associated ciliopathies
2017-02-15

Purpose of review To review disorders that are associated with renal cystic disease during prenatal life and to highlight the strong association between renal cystic disease and ciliopathies. Recent findings There are numerous causative genes for ciliopathies that can present with cystic kidney disease. In the group of single gene ciliopathies, autosomal dominant polycystic kidney disease is by far the most prevalent one. Other examples are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet–Biedl syndrome, Meckel–Gruber syndrome, Joubert syndrome and related disorders as well as X-linked orofaciodigital syndrome type 1, respectively. The prevalence of these inherited disorders sums up to about in 1 : 2000 people. These disorders with their hepatorenal fibrocystic character should be classified as multisystem diseases. Summary Understanding of the origin of renal cystic disease and associated disorders is important to make the appropriate prenatal diagnosis and for counseling affected parents. In the future, understanding of the pathophysiology may help to develop new treatment strategies.
Naturalistic path integration of Cataglyphis desert ants on an air-cushioned lightweight spherical treadmill
2017-02-15

ABSTRACT Air-cushioned spheres are widely used as treadmills to study behavioural and neurophysiological questions in numerous species. We describe an improved spherical treadmill design that reliably registers the path and walking behaviour of an animal walking on top of the sphere. The simple and robust set-up consists of a very light hollowed styrofoam ball supported by an air stream in a hollow half sphere and can be used indoors and outdoors. Two optical mouse sensors provided with lenses of 4.6 mm focal length detect the motion of the sphere with a temporal resolution of more than 200 frames s−1 and a spatial resolution of less than 0.2 mm. The treadmill can be used in an open- or closed-loop configuration with respect to yaw of the animal. The tethering allows animals to freely adjust their body posture and in the closed-loop configuration to quickly rotate around their yaw axis with their own moment of inertia. In this account, we present the first evidence of naturalistic homing navigation on a spherical treadmill for two species of Cataglyphis desert ants. We were able to evaluate with good precision the walking speed and angular orientation at any time. During homing the ants showed a significant difference in walking speed between the approach and search phases; moreover, they slowed down significantly as soon as they reached zero vector state, the fictive nest position.
A combinatorial approach to identify calpain cleavage sites in the Machado-Joseph disease protein ataxin-3
2017-02-15

Ataxin-3, the disease protein in Machado-Joseph disease, is known to be proteolytically modified by various enzymes including two major families of proteases, caspases and calpains. This processing results in the generation of toxic fragments of the polyglutamine-expanded protein. Although various approaches were undertaken to identify cleavage sites within ataxin-3 and to evaluate the impact of fragments on the molecular pathogenesis of Machado-Joseph disease, calpain-mediated cleavage of the disease protein and the localization of cleavage sites remained unclear. Here, we report on the first precise localization of calpain cleavage sites in ataxin-3 and on the characterization of the resulting breakdown products. After confirming the occurrence of calpain-derived fragmentation of ataxin-3 in patient-derived cell lines and post-mortem brain tissue, we combined in silico prediction tools, western blot analysis, mass spectrometry, and peptide overlay assays to identify calpain cleavage sites. We found that ataxin-3 is primarily cleaved at two sites, namely at amino acid positions D208 and S256 and mutating amino acids at both cleavage sites to tryptophan nearly abolished ataxin-3 fragmentation. Furthermore, analysis of calpain cleavage-derived fragments showed distinct aggregation propensities and toxicities of C-terminal polyglutamine-containing breakdown products. Our data elucidate the important role of ataxin-3 proteolysis in the pathogenesis of Machado-Joseph disease and further emphasize the relevance of targeting this disease pathway as a treatment strategy in neurodegenerative disorders.
Synchronous spikes are necessary but not sufficient for a synchrony code in populations of spiking neurons
2017-02-15

Significance Populations of sensory neurons convey information about the outside world to the brain. Postsynaptic neurons may read out their total activity or, alternatively, by focusing only on synchronous activity, they might extract specific features from the same sensory information. But does synchronous activity always encode special features of the stimulus? This question was experimentally addressed in in vivo recordings from two closely related populations of electrosensory neurons of a weakly electric fish. Despite having similar amounts of synchronous activity, only in one population of neurons did synchronous spikes carry specific information about the stimulus. A detailed spectral analysis reveals that too low levels of intrinsic noise paired with too little frequency locking of the neural oscillator destroys a synchrony code.
From Problem to Opportunity?: An Analytical Framework for Vagueness and Ambiguity in International Law
2017-02-15

As law hinges on the imprecise instrument that is language, legal norms or legally relevant acts, accordingly, often may be vague or ambiguous. International law is no exception in this regard. However, in international legal thinking on the interpretation of international norms or acts, vagueness and ambiguity (VaA) are usually perceived as a problem, an obscurity to be resolved. This contribution intends to take a fresh look at vagueness and ambiguity in this latter context. It will present an analytical framework systematizing five different categories of looking at VaA in interpreting international law and thereupon employ these categories to scrutinize, in descending order of abstraction, VaA’s implications vis-a-vis several issues of international legal thinking, including the exercise of authority and international adjudication. Thereby it seeks to demonstrate the benefits of moving vagueness and ambiguity from the periphery to the centre of international legal thinking on interpretation.
Feasibility of accelerated simultaneous multislice diffusion‐weighted MRI of the prostate
2017-02-15

Purpose To assess the feasibility of simultaneous multislice (SMS) single‐shot echo‐planar‐imaging (EPI) for accelerated diffusion‐weighted imaging (DWI) of the prostate. Materials and Methods For phantom measurements a dedicated DWI phantom with different sucrose concentrations was used. In addition, 10 volunteers and 16 patients with suspected prostate cancer were examined for in vivo measurements. All examinations were performed with a 3T magnetic resonance imaging (MRI) system. A prototype simultaneous multislice EPI sequence (DW‐EPI SMS ; acquisition time 3:14 min) was acquired and compared to a single‐shot EPI sequence (DW‐EPI SS ; acquisition time 6:12 min) serving as a standard of reference. Different image quality parameters of EPI SMS were assessed qualitatively (overall image quality, anatomic differentiability, lesion conspicuity, image noise, distortion; two independent readers; 5‐point Likert‐scale [5 = excellent]) and quantitatively (ADC‐values by calculating interclass correlation [ICC] and Bland–Altman limits of agreement [LoA] as measures for reproducibility) and compared to DW‐EPI SS . Results DW‐EPI SMS allowed for a substantially reduced acquisition time as compared to DW‐EPI SS ( ̃50%). Bland–Altman plots revealed robust measurement repeatability for DW‐EPI SMS in the phantom study. Overall image quality did not significantly differ between DW‐EPI SMS and DW‐EPI SS (b1500 images P = 0.5; ADC maps P = 0.7). Only in b1500 DW images was subjective image noise rated significantly higher in DW‐EPI SS than in DW‐EPI SMS ( P = 0.006). Quantitative analysis of ADC‐values revealed not significant differences between DW‐EPI SMS and DW‐EPI SS ( P = 0.7) and high measures for reproducibility ICC ≥0.96. Conclusion Simultaneous multislice DWI is feasible for accelerated prostate MRI allowing for a substantially reduced examination time with similar image quality and ADC‐values as compared to a standard of reference DWI sequence. Level of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1507–1515.
Taxonomical study on a sample of land and freshwater snails from caves in central Brazil, with description of a new species
2017-02-15

A sample of land and freshwater snails, mainly pulmonates, was recently collected in caves in Goiás and Bahia states, Brazil. Twenty-one species were found in the material. The following species are reported for the first time for Goiás state: Cecilioides consobrina (Ferussaciidae), Dysopeas muibum and Stenogyra octogyra (Subulinidae), Entodina jekylli and Prohappia besckei (Scolodontidae; also reported for the first time for Bahia state), Pupisoma dioscoricola (Valloniidae). A new species from Goiás is described herein: Gastrocopta sharae sp. n. (Gastrocoptidae). The new records and species addressed here constitute important findings, helping to fill distributional gaps and improving the knowledge of the local molluscan fauna, an essential step for future conservation efforts.
How to Study Consciousness in Consumer Research, A Commentary on Williams and Poehlman
2017-02-15

Consumer research can benefit greatly from more insight into unconscious processes underlying behavior. Williams and Poehlman's effort at more clearly conceptualizing consciousness and call for more research provides a welcome stimulus in this regard. At the same time, providing evidence for unconscious causation is fraught with methodological difficulties. We outline why it is vital to uphold standards of evidence for claims regarding unconscious processes, as it is precisely a lack of rigor on this front that has generated a countermovement by researchers skeptical of dual-process models in general and unconscious processes in particular. We contend that the skeptics have offered valid causes for concern, which we leverage to formulate six concrete recommendations for future research on consciousness. Researchers should (1) specify the process level at which they claim evidence for unconscious processes, (2) not confuse unconscious influences with unconscious processes, (3) carefully choose between different operational definitions of awareness, (4) maximally satisfy four criteria for awareness measures, and (5) complement measurement with experimental manipulations of awareness. Finally, we recommend to (6) refrain from hard claims about unconscious causation that transcend the limitations of the evidence, recognizing that consciousness is a continuous construct.
Monitoring and analysis of the change process in curriculum mapping compared to the National Competency-based Learning Objective Catalogue for Undergraduate Medical Education (NKLM) at four medical faculties. Part II: Key factors for motivating the faculty during the process
2017-02-15

Objective: After adoption of the National Competency-based Learning Objectives Catalogue in Medicine [Nationaler Kompetenzbasierter Lernzielkatalog Medizin, [link:NKLM*http://www.nklm.de]], the German medical faculties are asked to test the learning obejctives recorded in it and evaluate them critically. The faculties require curricular transparency for competence-oriented transition of present curricula, which is best achieved by systematic curriculum mapping in comparison to the NKLM. Based on this inventory, curricula can be further developed target-oriented. Considerable resistance has to be expected when a complex existing curriculum is to be mapped for the first time and a faculty must be convinced of its usefulness. Headed by Tübingen, the faculties of Freiburg, Heidelberg, Mannheim and Tübingen rose to this task. This two-part article analyses and summarises how NKLM curriculum mapping was successful at the locations despite resistance. Part I presented the resources and structures that supported implementation. Part II focuses on factors that motivate individuals and groups of persons to cooperate in the faculties. Method: Both parts used the same method. In short, the joint project was systematically planned following the steps of project and change management and adjusted in the course of the process. From the beginning of the project, a Grounded-Theory approach was used to systematically collect detailed information on measures and developments at the faculties, to continually analyse them and to draw final conclusions. Results: At all sites, faculties, teachers, students and administrative staff were not per se willing to deal with the NKLM and its contents, and even less to map their present curricula. Analysis of the development reflected a number of factors that had either a negative effect on the willingness to cooperate when missing, or a positive one when present. These were: clear top-down and bottom-up management; continuous information of the faculty; user-oriented support in the mapping process by reduction of the mapping categories, portioning and condensation of the NKLM via student pre-mapping (blueprint) and visibility of growing consent. Apart from that, there were a series of frequent questions, objections and concerns that could be countered strategically and by argumentation. They particularly referred to relevance, benefit, feasibility and effort of curriculum mapping. Conclusion: An overview of beneficial framework conditions, strategies and results from different points of view is achieved and interrelations are made visible. Based on literature results, the motivating factors as well as their implementation and effects in the faculties involved are critically reflected on. Recommendations can be derived that can support other faculties in practice.