julilili42/papers huggingface dataset:
Techniques for the analysis of protein-protein interactions in vivo
2016-04-25

Identifying key players and their interactions is fundamental for understanding biochemical mechanisms at the molecular level. The ever-increasing number of alternative ways to detect protein-protein interactions (PPIs) speaks volumes about the creativity of scientists in hunting for the optimal technique. PPIs derived from single experiments or high-throughput screens enable the decoding of binary interactions, the building of large-scale interaction maps of single organisms, and the establishment of cross-species networks. This review provides a historical view of the development of PPI technology over the past three decades, particularly focusing on in vivo PPI techniques that are inexpensive to perform and/or easy to implement in a state-of-the-art molecular biology laboratory. Special emphasis is given to their feasibility and application for plant biology as well as recent improvements or additions to these established techniques. The biology behind each method and its advantages and disadvantages are discussed in detail, as are the design, execution, and evaluation of PPI analysis. We also aim to raise awareness about the technological considerations and the inherent flaws of these methods, which may have an impact on the biological interpretation of PPIs. Ultimately, we hope this review serves as a useful reference when choosing the most suitable PPI technique.
Loss of functional OPA 1 unbalances redox state: implications in dominant optic atrophy pathogenesis
2016-04-25

Our study suggests that the pro-oxidative state induced by OPA1 loss may contribute to DOA pathogenesis and that differences in antioxidant defenses can explain the variability in expressivity. Furthermore, antioxidants may be used as therapy as they could prevent or delay DOA symptoms in patients.
The rate and potential relevance of new mutations in a colonizing plant lineage
2016-04-25

ABSTRACT By following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence of de novo mutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by “natural evolution experiments” that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plant Arabidopsis thaliana , and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions – the subset of mutations that survived natural selection and drift –, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17 th century, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.
Locally rare species influence grassland ecosystem multifunctionality
2016-04-26

Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity–multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
Shells of charge: a density functional theory for charged hard spheres
2016-04-26

A functional for the electrostatic excess free-energy for charged, hard sphere fluids is proposed. The functional is derived from two complementary, but equivalent, interpretations of the mean spherical approximation (MSA). The first combines fundamental measure theory (FMT) from hard-core interactions with the idea that MSA can be interpreted in terms of the interaction spherical shells of charge. This formulation gives the free-energy density as a function of weighted densities. When all the ions have the same size, the functional adopts an FMT-like form. The second in effect 'functionalizes' the derivation of MSA; that is, it generalizes the MSA as a functional-based version of MSA (fMSA). This formulation defines the free-energy density as a function of a position-dependent MSA screening parameter and the weighted densities of the FMT approach. This FMT/fMSA functional is shown to give accurate density profiles, as compared to Monte Carlo simulations, under a wide range of ion concentrations, size asymmetries, and valences.
RpiRc Is a Pleiotropic Effector of Virulence Determinant Synthesis and Attenuates Pathogenicity in Staphylococcus aureus
2016-04-26

ABSTRACT In Staphylococcus aureus , metabolism is intimately linked with virulence determinant biosynthesis, and several metabolite-responsive regulators have been reported to mediate this linkage. S. aureus possesses at least three members of the RpiR family of transcriptional regulators. Of the three RpiR homologs, RpiRc is a potential regulator of the pentose phosphate pathway, which also regulates RNAIII levels. RNAIII is the regulatory RNA of the agr quorum-sensing system that controls virulence determinant synthesis. The effect of RpiRc on RNAIII likely involves other regulators, as the regulators that bind the RNAIII promoter have been intensely studied. To determine which regulators might bridge the gap between RpiRc and RNAIII, sarA , sigB , mgrA , and acnA mutations were introduced into an rpiRc mutant background, and the effects on RNAIII were determined. Additionally, phenotypic and genotypic differences were examined in the single and double mutant strains, and the virulence of select strains was examined using two different murine infection models. The data suggest that RpiRc affects RNAIII transcription and the synthesis of virulence determinants in concert with σ B , SarA, and the bacterial metabolic status to negatively affect virulence.
German Center Subanalysis of the LEVANT 2 Global Randomized Study of the Lutonix Drug-Coated Balloon in the Treatment of Femoropopliteal Occlusive Disease
2016-04-26

Purpose: To report a subanalysis of the German centers enrolling patients in the prospective, global, multicenter, randomized LEVANT 2 pivotal trial ( ClinicalTrials.gov identifier NCT01412541) of the Lutonix drug-coated balloon (DCB) for the treatment of femoropopliteal occlusive disease. Methods: Among the 476 patients in LEVANT 2, 126 patients (mean age 67.1±9.6 years; 79 men) were enrolled at the 8 participating German sites between August 2011 and July 2012 and were randomized 2:1 to treatment with the Lutonix DCB (n=83) vs an uncoated balloon during percutaneous transluminal angioplasty (PTA, n=43). All patients had intermittent claudication or rest pain (Rutherford categories 2–4). Average lesion length was 58 mm and average treated length was 100 mm. Severe calcification was present in 11% of lesions, and 23% were total occlusions. The efficacy outcome was primary patency at 12 months, and the safety outcome was 12-month freedom from a composite of perioperative death, index limb–related death, amputation (below or above the ankle), and index limb revascularization. Secondary endpoints included target lesion revascularization (TLR), major adverse events, and functional outcomes. Results: Demographic, clinical, and lesion characteristics were matched between Lutonix DCB and PTA groups, as were the final percent diameter stenosis (19%) and procedure success (91%). By Kaplan-Meier analysis, the 12-month primary patency rate was 80% vs 58% (p=0.015) and the composite safety endpoint rate was 94% vs 72% (p=0.001), respectively. Freedom from TLR was higher for DCBs (96%) vs PTA (82%, p=0.012). Major adverse events were similar for both groups. The benefit favoring DCB over PTA was observed in German men and women. Compared to the non-German LEVANT 2 cohort, there was a shorter time between insertion and inflation of treatment balloons (21.8 vs 39.5 seconds, p&lt;0.001) in the German cohort. Balloons were inflated to higher pressures (9.0 vs 7.7 atm, p&lt;0.001) but for a shorter period of time (130 vs 167 seconds, p&lt;0.001), and although treated lesions in the German cohort had a higher baseline stenosis, final postprocedure diameter stenosis was lower (19% vs 22%, p=0.04) than in the non-German patients. Conclusion: Superiority of DCB over PTA in the German cohort of LEVANT 2 was demonstrated for primary patency, composite safety, and freedom from TLR. The benefit of DCB was also consistent for both genders. Geographic or regional differences in procedural variables may account for the different outcomes between the German and non-German cohorts.
Access to Base Adducts of Low‐Valent Organotin‐Hydride Compounds by Controlled, Stepwise Hydrogen Abstraction from a Tetravalent Organotin Trihydride
2016-04-26

Abstract Hydrogen can be selectively removed from organotin trihydrides to generate the corresponding organohydrostannylene intermediates. Depending on the size of the substituent and the mode of generation, the intermediates undergo further reactions. Herein, we report on the formation of a variety of organotin hydrides with tin in the oxidation states Sn II , Sn I –Sn III and Sn III –Sn III , all accessed by the controlled removal of hydrogen from the tetravalent Ar′Sn IV trihydride (Ar′=2,6‐dimesitylphenyl, mesityl=2,4,6‐trimethylphenyl).
Association of Plasma Aβ40 Peptides, But Not Aβ42, with Coronary Artery Disease and Diabetes Mellitus
2016-04-26

Our findings argue for an association of circulating plasma Aβ1 - 40 peptides with incident CAD and DM. Further investigations are needed to entangle the role of Aβ1 - 40 role in the pathophysiology of cardiovascular disease independent of its known role in Alzheimer's disease.
Density functional theory for polymeric systems in 2D
2016-04-26

We propose density functional theory for polymeric fluids in two dimensions. The approach is based on Wertheim's first order thermodynamic perturbation theory (TPT) and closely follows density functional theory for polymers proposed by Yu and Wu (2002 J. Chem. Phys. 117 2368). As a simple application we evaluate the density profiles of tangent hard-disk polymers at hard walls. The theoretical predictions are compared against the results of the Monte Carlo simulations. We find that for short chain lengths the theoretical density profiles are in an excellent agreement with the Monte Carlo data. The agreement is less satisfactory for longer chains. The performance of the theory can be improved by recasting the approach using the self-consistent field theory formalism. When the self-avoiding chain statistics is used, the theory yields a marked improvement in the low density limit. Further improvements for long chains could be reached by going beyond the first order of TPT.
Long-range weight functions in fundamental measure theory of the non-uniform hard-sphere fluid
2016-04-26

We introduce long-range weight functions to the framework of fundamental measure theory (FMT) of the non-uniform, single-component hard-sphere fluid. While the range of the usual weight functions is equal to the hard-sphere radius R, the modified weight functions have range 3R. Based on the augmented FMT, we calculate the radial distribution function g(r) up to second order in the density within Percus' test particle theory. Consistency of the compressibility and virial routes on this level allows us to determine the free parameter γ of the theory. As a side result, we obtain a value for the fourth virial coefficient B 4 which deviates by only 0.01% from the exact result. The augmented FMT is tested for the dense fluid by comparing results for g(r) calculated via the test particle route to existing results from molecular dynamics simulations. The agreement at large distances (r > 6R) is significantly improved when the FMT with long-range weight functions is used. In order to improve agreement close to contact (r = 2R) we construct a free energy which is based on the accurate Carnahan-Starling equation of state, rather than the Percus-Yevick compressibility equation underlying standard FMT.
A fundamental measure density functional for fluid and crystal phases of the Asakura–Oosawa model
2016-04-26

We investigate a density functional for the Asakura-Oosawa model of colloid-polymer mixtures, describing both fluid and crystal phases. It is derived by linearizing the two-component fundamental-measure hard sphere tensor functional in the second (polymer) component. We discuss the formulation of an effective density functional for colloids only. For small polymer-colloid size ratios the effective, polymer-induced potential between colloids is short-range attractive and of two-body form but we show that the effective density functional is not equivalent to standard mean-field approaches where attractions are taken into account by terms second order in the colloid density. We calculate numerically free energies and phase diagrams in good agreement with available simulations, furthermore we discuss the colloid and polymer distributions in the crystal and determine equilibrium vacancy concentrations. Numerical results reveal a fairly strong sensitivity to the specific type of underlying fundamental measure hard sphere functional which could aid further development of fundamental measure theory.
MALT: Fast alignment and analysis of metagenomic DNA sequence data applied to the Tyrolean Iceman
2016-04-27

Abstract Modern next generation sequencing technologies produce vast amounts of data in the context of large-scale metagenomic studies, in which complex microbial communities can be reconstructed to an unprecedented level of detail. Most prominent examples are human microbiome studies that correlate the bacterial taxonomic profile with specific physiological conditions or diseases. In order to perform these analyses high-throughput computational tools are needed that are able to process these data within a short time while preserving a high level of sensitivity and specificity. Here we present MALT ( ME GAN AL ignment T ool) a program for the ultrafast alignment and analysis of metagenomic DNA sequencing data. MALT processes hundreds of millions of sequencing reads within only a few hours. In addition to the alignment procedure MALT implements a taxonomic binning algorithm that is able to specifically assign reads to bacterial species. Its tight integration with the interactive metagenomic analysis software MEGAN allows for visualization and further analyses of results. We demonstrate MALT by its application to the metagenomic analysis of two ancient microbiomes from oral cavity and lung samples of the 5,300-year-old Tyrolean Iceman. Despite the strong environmental background, MALT is able to pick up the weak signal of the original microbiomes and identifies multiple species that are typical representatives of the respective host environment.
Neandertal versus Modern Human Dietary Responses to Climatic Fluctuations
2016-04-27

The Neandertal lineage developed successfully throughout western Eurasia and effectively survived the harsh and severely changing environments of the alternating glacial/interglacial cycles from the middle of the Pleistocene until Marine Isotope Stage 3. Yet, towards the end of this stage, at the time of deteriorating climatic conditions that eventually led to the Last Glacial Maximum, and soon after modern humans entered western Eurasia, the Neandertals disappeared. Western Eurasia was by then exclusively occupied by modern humans. We use occlusal molar microwear texture analysis to examine aspects of diet in western Eurasian Paleolithic hominins in relation to fluctuations in food supplies that resulted from the oscillating climatic conditions of the Pleistocene. There is demonstrable evidence for differences in behavior that distinguish Upper Paleolithic humans from members of the Neandertal lineage. Specifically, whereas the Neandertals altered their diets in response to changing paleoecological conditions, the diets of Upper Paleolithic humans seem to have been less affected by slight changes in vegetation/climatic conditions but were linked to changes in their technological complexes. The results of this study also indicate differences in resource exploitation strategies between these two hominin groups. We argue that these differences in subsistence strategies, if they had already been established at the time of the first contact between these two hominin taxa, may have given modern humans an advantage over the Neandertals, and may have contributed to the persistence of our species despite habitat-related changes in food availabilities associated with climate fluctuations.
The Severe Respiratory Insufficiency Questionnaire for Subjects With COPD With Long-Term Oxygen Therapy
2016-04-27

The SRI showed high reliability and validity in subjects with COPD receiving LTOT. Subjects receiving LTOT had lower SRI scores, indicating a poorer HRQOL compared with subjects with established NIV and LTOT.
Evaluation of semi-arid arable soil heavy metal pollution by magnetic susceptibility in the Linfen basin of China
2016-04-27

The values of magnetic susceptibility and Cu, Zn, Ni, Pb, Cr, Cd concentrations of 70 topsoil samples were analyzed and assessed for soil contamination in the Linfen basin of China. The contamination factor (CF) and pollution load index (PLI) were used to assess the degree of heavy metal pollution. All heavy metal concentrations in the soil were greater than the background values of Shanxi agricultural soils. PLI values ranged from 1.27 to 2.18 indicating significant soil contamination. Principal component analyses and correlation analyses were adopted for data treatment to identify heavy metal sources. Cu, Zn, Ni, and Pb were responsible for 31.2% of the total variance suggesting that these elements mainly originated from agrochemistry and atmospheric deposition. A positive correlation of magnetic susceptibility with Cu and PLI were observed in cultivated soils. This study shows that magnetic susceptibility measurements can be used as a technique in which different types of soil pollution can be distinguished and can also be used to rapidly monitor anomalies in areas that might require expensive and time consuming detailed chemical analyses.
A study for testing the Kerr metric with AGN iron line eclipses
2016-04-27

Recently, two of us have studied iron line reverberation mapping to test black hole candidates, showing that the time information in reverberation mapping can better constrain the Kerr metric than the time-integrated approach. Motivated by this finding, here we explore the constraining power of another time-dependent measurement: an AGN iron line eclipse. An obscuring cloud passes between the AGN and the distant observer, covering different parts of the accretion disk at different times. Similar to the reverberation measurement, an eclipse might help to better identify the relativistic effects affecting the X-ray photons. However, this is not what we find. In our study, we employ the Johannsen-Psaltis parametrisation, but we argue that our conclusions hold in a large class of non-Kerr metrics. We explain our results pointing out an important difference between reverberation and eclipse measurements.
Morningness–eveningness and amplitude – development and validation of an improved composite scale to measure circadian preference and stability (MESSi)
2016-04-28

Measuring morningness-eveningness is an important aspect of individual differences because it is associated with many aspects of personality and health. The present study outlines recent advancements in the field of measurement and proposes an improved assessment of morningness-eveningness, such as the measurement of circadian amplitude, updating and reflecting new item developments, addressing the clock time based measures, the morning-biased items and the aspect of uni versus multidimensionality. Four studies have been carried out in Germany to present a novel development (with a total sample of N = 1181). In study I, the exploratory factor analysis (EFA) revealed three dimensions, one of morningness, one of eveningness and one of amplitude/stability. Then, items were reduced to present a clearer factor structure by removing ambiguous items. In the second study, a shortened questionnaire was applied, with 15 items (5 per construct), but Confirmatory Factor Analysis (CFA) did not provide acceptable fit indices. Refining items were made in study III, which again showed a clearer factor structure in EFA, and subsequently, in study IV, the refined set of 15 items provided a good fit of a CFA. The final questionnaire was tested for validity by applying clock times, personality questions and alertness ratings. Thus, this newly developed questionnaire contains three distinct dimensions. To reflect the new content, the scale is labelled morningness-eveningness-stability-scale improved (MESSi).
Recent advances in understanding psoriasis
2016-04-28

<ns4:p>T helper (Th) cells producing interleukin (IL)-17, IL-22, and tumor necrosis factor (TNF) form the key T cell population driving psoriasis pathogenesis. They orchestrate the inflammation in the skin that results in the proliferation of keratinocytes and endothelial cells. Besides Th17 cells, other immune cells that are capable of producing IL-17-associated cytokines participate in psoriatic inflammation. Recent advances in psoriasis research improved our understanding of the cellular and molecular players that are involved in Th17 pathology and inflammatory pathways in the skin. The inflammation-driving actions of TNF in psoriasis are already well known and antibodies against TNF are successful in the treatment of Th17-mediated psoriatic skin inflammation. A further key cytokine with potent IL-17-/IL-22-promoting properties is IL-23. Therapeutics directly neutralizing IL-23 or IL-17 itself are now extending the therapeutic spectrum of antipsoriatic agents and further developments are on the way. The enormous progress in psoriasis research allows us to control this Th17-mediated inflammatory skin disease in many patients.</ns4:p>