bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Small Molecules Targeting the Intrinsically Disordered Structural Ensemble of α-Synuclein Protect Against Diverse α-Synuclein Mediated Dysfunctions
Authors: Tóth Gergely , Neumann Thomas , Berthet Amandine , Masliah Eliezer , Spencer Brian , Tao Jiahui , Jobling Michael F. , Gardai Shyra J. , Bertoncini Carlos W. , Cremades Nunilo , Bova Michael , Ballaron Stephen , Chen Xiao-Hua , Mao Wenxian , Nguyen Phuong , Tabios Mariano C. , Tambe Mitali A. , Rochet Jean-Christophe , Junker Hans-Dieter , Schwizer Daniel , Sekul Renate , Ott Inge , Anderson John P. , Szoke Balazs , Hoffman Wherly , Christodoulou John , Yednock Ted , Agard David A. , Schenk Dale , McConlogue Lisa 
Published: November 2019

AbstractThe over-expression and aggregation of α-synuclein (αSyn) are linked to the onset and pathology of Parkinson’s disease. Native monomeric αSyn exists in an intrinsically disordered ensemble of interconverting conformations, which has made its therapeutic targeting by small molecules highly challenging. Nonetheless, here we successfully target the monomeric structural ensemble of αSyn and thereby identify novel drug-like small molecules that impact multiple pathogenic processes. Using a surface plasmon resonance high-throughput screen, in which monomeric αSyn is incubated with microchips arrayed with tethered compounds, we identified novel αSyn interacting drug-like compounds. Because these small molecules could impact a variety of αSyn forms present in the ensemble, we tested representative hits for impact on multiple αSyn malfunctions in vitro and in cells including aggregation and perturbation of vesicular dynamics. We thereby identified a compound that inhibits αSyn misfolding and is neuroprotective, multiple compounds that restore phagocytosis impaired by αSyn overexpression, and a compound blocking cellular transmission of αSyn. Our studies demonstrate that drug-like small molecules that interact with native αSyn can impact a variety of its pathological processes. Thus, targeting the intrinsically disordered ensemble of αSyn offers a unique approach to the development of small molecule research tools and therapeutics for Parkinson’s disease.
Coincidence of photic zone euxinia and impoverishment of arthropods in the aftermath of the Frasnian-Famennian biotic crisis
Authors: Broda Krzysztof , Marynowski Leszek , Rakociński Michał , Zatoń Michał 
Published: November 2019

AbstractThe lowermost Famennian deposits of the Kowala quarry (Holy Cross Mountains, Poland) are becoming famous for their rich fossil content such as their abundant phosphatized arthropod remains (mostly thylacocephalans). Here, for the first time, palaeontological and geochemical data were integrated to document abundance and diversity patterns in the context of palaeoenvironmental changes. During deposition, the generally oxic to suboxic conditions were interrupted at least twice by the onset of photic zone euxinia (PZE). Previously, PZE was considered as essential in preserving phosphatised fossils from, e.g., the famous Gogo Formation, Australia. Here, we show, however, that during PZE, the abundance of arthropods drastically dropped. The phosphorous content during PZE was also very low in comparison to that from oxic-suboxic intervals where arthropods are the most abundant. As phosphorous is essential for phosphatisation but also tends to flux off the sediment during bottom water anoxia, we propose that the PZE in such a case does not promote the fossilisation of the arthropods but instead leads to their impoverishment and non-preservation. Thus, the PZE conditions with anoxic bottom waters cannot be presumed as universal for exceptional fossil preservation by phosphatisation, and caution must be paid when interpreting the fossil abundance on the background of redox conditions.
The impact of Climate Change on the Western Pacific Subtropical High and the related ozone pollution in Shanghai, China
Authors: Chang Luyu , Xu Jianming , Tie Xuexi , Gao Wei 
Published: November 2019

AbstractSevere ozone (O3) episodes occur frequently in Shanghai during late-summers. We define geopotential height averaged over the key area region (122.5°E-135°E, 27.5°N -35°N) at 500 hPa as a WPSH_SHO3 index which has high positive correlation with surface O3 concentration in Shanghai. In addition, the index has a significant long-term increasing trend during the recent 60 years. Analysis shows the meteorological conditions under the strong WPSH_SHO3 climate background (compared to the weak background) have several important anomalies: (1) A strong WPSH center occurs over the key area region. (2) The cloud cover is less, resulting in high solar radiation and low humidity, enhancing the photochemical reactions of O3. (3) The near-surface southwesterly winds are more frequent, enhancing the transport of upwind pollutants and O3 precursors from polluted regions to Shanghai and producing higher O3 chemical productions. This study suggests that the global climate change could lead to a stronger WPSH in the key region, enhancing ozone pollution in Shanghai. A global chemical/transport model (MOZART-4) is applied to show that the O3 concentrations can be 30 ppbv higher under a strong WPSH_SHO3 condition than a weak condition, indicating the important effect of the global climate change on local air pollution in Shanghai.
Different lasers reveal different skin microcirculatory flowmotion - data from the wavelet transform analysis of human hindlimb perfusion
Authors: Rodrigues L. Monteiro , Rocha Clemente , Ferreira Hugo , Silva Henrique 
Published: November 2019

AbstractLaser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG) are standard technologies to access microcirculatory function in vivo. However, different light frequencies mean different interaction with tissues, such that LDF and PPG flowmotion curves might have distinct meanings, particularly during adaptative (homeostatic) processes. Therefore, we analyzed LDF and PPG perfusion signals obtained in response to opposite challenges. Young healthy volunteers, both sexes, were assigned to Group 1 (n = 29), submitted to a normalized Swedish massage procedure in one lower limb, increasing perfusion, or Group 2 (n = 14), submitted to a hyperoxia challenge test, decreasing perfusion. LDF (Periflux 5000) and PPG (PLUX-Biosignals) green light sensors applied distally on both lower limbs recorded perfusion changes for each experimental protocol. Both techniques detected the perfusion increase with massage, and the perfusion decrease with hyperoxia, in both limbs. Further analysis with the wavelet transform (WT) revealed better depth-related discriminative ability for PPG (more superficial, less blood sampling) compared with LDF in both challenges. Spectral amplitude profiles consistently demonstrated better sensitivity for LDF, especially regarding the lowest frequency components. Strong correlations between components were not found. Therefore, LDF and PPG flowmotion curves are not equivalent, a relevant finding to better study microcirculatory physiology.
Genomic Patterns of Homozygosity in Chinese Local Cattle
Authors: Xu Lingyang , Zhao Guoyao , Yang Liu , Zhu Bo , Chen Yan , Zhang Lupei , Gao Xue , Gao Huijiang , Liu George E. , Li Junya 
Published: November 2019

AbstractGenome-wide single nucleotide polymorphism (SNP) arrays can be used to explore homozygosity segments, where two haplotypes inherited from the parents are identical. In this study, we identified a total of 27,358 runs of homozygosity (ROH) with an average of 153 ROH events per animal in Chinese local cattle. The sizes of ROH events varied considerably ranging from 0.5 to 66 Mb, with an average length of 1.22 Mb. The highest average proportion of the genome covered by ROH (~11.54% of the cattle genome) was found in Nanda cattle (NDC) from South China, whereas the lowest average proportion (~3.1%) was observed in Yanhuang cattle (YHC). The average estimated FROH ranged from 0.03 in YHC to 0.12 in NDC. For each of three ROH classes with different sizes (Small 0.5–1 Mb, Medium 1–5 Mb and Large >5 Mb), the numbers and total lengths of ROH per individual showed considerable differences across breeds. Moreover, we obtained 993 to 3603 ROH hotspots (which were defined where ROH frequency at a SNP within each breed exceeded the 1% threshold) among eight cattle breeds. Our results also revealed several candidate genes embedded with ROH hotspots which may be related to environmental conditions and local adaptation. In conclusion, we generated baselines for homozygosity patterns in diverse Chinese cattle breeds. Our results suggested that selection has, at least partially, played a role with other factors in shaping the genomic patterns of ROH in Chinese local cattle and might provide valuable insights for understanding the genetic basis of economic and adaptive traits.
Relativistic quantum heat engine from uncertainty relation standpoint
Authors: Chattopadhyay Pritam , Paul Goutam 
Published: November 2019

AbstractEstablished heat engines in quantum regime can be modeled with various quantum systems as working substances. For example, in the non-relativistic case, we can model the heat engine using infinite potential well as a working substance to evaluate the efficiency and work done of the engine. Here, we propose quantum heat engine with a relativistic particle confined in the one-dimensional potential well as working substance. The cycle comprises of two isothermal processes and two potential well processes of equal width, which forms the quantum counterpart of the known isochoric process in classical nature. For a concrete interpretation about the relation between the quantum observables with the physically measurable parameters (like the efficiency and work done), we develop a link between the thermodynamic variables and the uncertainty relation. We have used this model to explore the work extraction and the efficiency of the heat engine for a relativistic case from the standpoint of uncertainty relation, where the incompatible observables are the position and the momentum operators. We are able to determine the bounds (the upper and the lower bounds) of the efficiency of the heat engine through the thermal uncertainty relation.
VAR2CSA binding phenotype has ancient origin and arose before Plasmodium falciparum crossed to humans: implications in placental malaria vaccine design
Authors: Gangnard Stéphane , Chêne Arnaud , Dechavanne Sébastien , Srivastava Anand , Avril Marion , Smith Joseph D. , Gamain Benoît 
Published: November 2019

AbstractVAR2CSA is a leading candidate for developing a placental malaria (PM) vaccine that would protect pregnant women living in malaria endemic areas against placental infections and improve birth outcomes. Two VAR2CSA-based PM vaccines are currently under clinical trials, but it is still unclear if the use of a single VAR2CSA variant will be sufficient to induce a broad enough humoral response in humans to cross-react with genetically diverse parasite populations. Additional immuno-focusing vaccine strategies may therefore be required to identify functionally conserved antibody epitopes in VAR2CSA. We explored the possibility that conserved epitopes could exist between VAR2CSA from the chimpanzee parasite Plasmodium reichenowi and Plasmodium falciparum sequences. Making use of VAR2CSA recombinant proteins originating from both species, we showed that VAR2CSA from P. reichenowi (Pr-VAR2CSA) binds to the placental receptor CSA with high specificity and affinity. Antibodies raised against Pr-VAR2CSA were able to recognize native VAR2CSA from different P. falciparum genotypes and to inhibit the interaction between CSA and P. falciparum-infected erythrocytes expressing different VAR2CSA variants. Our work revealed the existence of cross-species inhibitory epitopes in VAR2CSA and calls for pre-clinical studies assessing the efficacy of novel VAR2CSA-based cross-species boosting regimens.
Functional tunability from a distance: Rheostat positions influence allosteric coupling between two distant binding sites
Authors: Wu Tiffany , Swint-Kruse Liskin , Fenton Aron W. 
Published: November 2019

AbstractFor protein mutagenesis, a common expectation is that important positions will behave like on/off “toggle” switches (i.e., a few substitutions act like wildtype, most abolish function). However, there exists another class of important positions that manifests a wide range of functional outcomes upon substitution: “rheostat” positions. Previously, we evaluated rheostat positions located near the allosteric binding sites for inhibitor alanine (Ala) and activator fructose-1,6-bisphosphate (Fru-1,6-BP) in human liver pyruvate kinase. When substituted with multiple amino acids, many positions demonstrated moderate rheostatic effects on allosteric coupling between effector binding and phosphoenolpyruvate (PEP) binding in the active site. Nonetheless, the combined outcomes of all positions sampled the full range of possible allosteric coupling (full tunability). However, that study only evaluated allosteric tunability of “local” positions, i.e., positions were located near the binding sites of the allosteric ligand being assessed. Here, we evaluated tunability of allosteric coupling when mutated sites were distant from the allosterically-coupled binding sites. Positions near the Ala binding site had rheostatic outcomes on allosteric coupling between Fru-1,6-BP and PEP binding. In contrast, positions in the Fru-1,6-BP site exhibited modest effects on coupling between Ala and PEP binding. Analyzed in aggregate, both PEP/Ala and PEP/Fru-1,6-BP coupling were again fully tunable by amino acid substitutions at this limited set of distant positions. Furthermore, some positions exhibited rheostatic control over multiple parameters and others exhibited rheostatic effects on one parameter and toggle control over a second. These findings highlight challenges in efforts to both predict/interpret mutational outcomes and engineer functions into proteins.
Comparison of pressure- and volume-controlled ventilation during laparoscopic colectomy in patients with colorectal cancer
Authors: Choi Sangbong , Yang So Young , Choi Geun Joo , Kim Beom Gyu , Kang Hyun 
Published: November 2019

AbstractThis study investigated the differences in airway mechanics and postoperative respiratory complications using two mechanical ventilation modalities and the relationship between biomarkers and postoperative respiratory complications in patients with colorectal cancer who underwent laparoscopic colectomy. Forty-six patients with colorectal cancer scheduled for laparoscopic colectomy were randomly allocated to receive mechanical ventilation using either volume-controlled ventilation (VCV) (n = 23) or pressure-controlled ventilation (PCV) (n = 23). Respiratory parameters were measured and plasma sRAGE and S100A12 were collected 20 minutes after the induction of anesthesia in the supine position without pneumoperitoneum (T1), 40 minutes after 30° Trendelenburg position with pneumoperitoneum (T2), at skin closure in the supine position (T3), and 24 hours after the operation (T4). The peak airway pressure (Ppeak) at T2 was lower in the PCV group than in the VCV group. The plateau airway pressures (Pplat) at T2 and T3 were higher in the VCV group than in the PCV group. Plasma levels of sRAGE at T2 and T3 were 1.6- and 1.4-fold higher in the VCV group than in the PCV group, while plasma S100A12 levels were 2.6- and 2.2-fold higher in the VCV group than in the PCV group, respectively. There were significant correlations between Ppeak and sRAGE, and between Ppeak and S100A12. There were also correlations between Pplat and sRAGE, and between Pplat and S100A12. sRAGE and S100A12 levels at T2 and T3 showed high sensitivity and specificity for postoperative respiratory complications. Postoperative respiratory complications were 3-fold higher in the VCV group than in the PCV group. In conclusion, during laparoscopic colectomy in patients with colorectal cancer, the peak airway pressure, the incidence of postoperative respiratory complications, and plasma sRAGE and S100A12 levels were lower in the PCV group than in the VCV group. Intra- and postoperative plasma sRAGE and S100A12 were useful for predicting the development of postoperative respiratory complications.
Association of longitudinal risk profile trajectory clusters with adipose tissue depots measured by magnetic resonance imaging
Authors: Rospleszcz Susanne , Lorbeer Roberto , Storz Corinna , Schlett Christopher L. , Meisinger Christa , Thorand Barbara , Rathmann Wolfgang , Bamberg Fabian , Lieb Wolfgang , Peters Annette 
Published: November 2019

AbstractThe objective of the study was to identify associations of longitudinal trajectories of traditional cardiometabolic risk factors with abdominal and ectopic adipose tissue depots measured by magnetic resonance imaging (MRI). We measured total abdominal, visceral, and subcutaneous adipose tissue in liter and intrahepatic, intrapancreatic and renal sinus fat as fat fractions by MRI in 325 individuals free of cardiovascular disease at Exam 3 of a population-based cohort. We related these MRI measurements at Exam 3 to longitudinal risk profile trajectory clusters, based on risk factor measurements from Exam 3, Exam 2 (seven years prior to MRI) and Exam 1 (14 years prior to MRI). Based on the levels and longitudinal trajectories of several risk factors (blood pressure, lipid profile, anthropometric measurements, HbA1c), we identified three different trajectory clusters. These clusters displayed a graded association with all adipose tissue traits after adjustment for potential confounders (e.g. visceral adipose tissue: βClusterII = 1.30 l, 95%-CI:[0.84 l;1.75 l], βClusterIII = 3.32 l[2.74 l;3.90 l]; intrahepatic: EstimateClusterII = 1.54[1.27,1.86], EstimateClusterIII = 2.48[1.93,3.16]. Associations remained statistically significant after additional adjustment for the risk factor levels at Exam 1 or Exam 3, respectively. Trajectory clusters provided additional information in explaining variation in the different fat compartments beyond risk factor profiles obtained at individual exams. In conclusion, sustained high risk factor levels and unfavorable trajectories are associated with high levels of adipose tissue; however, the association with cardiometabolic risk factors varies substantially between different ectopic adipose tissues. Trajectory clusters, covering longitudinal risk profiles, provide additional information beyond single-point risk profiles. This emphasizes the need to incorporate longitudinal information in cardiometabolic risk estimation.
Surface effects on the self equilibrium, self bending and symmetry lowering of nanofilms
Authors: Li Jiangang , Han Meiqin , Li Lingfang , Gao Zhixiang , Zhang Huili 
Published: November 2019

AbstractA continuum theoretical scheme for self equilibrium, self bending and symmetry lowering of nanofilms was obtained by considering surface elasticity, surface stress and the corresponding surface slice thickness. When surface stress and surface elasticity are both balance, the nanofilm is simply compressed (or expanded). When the surface stress or surface elasticity is imbalance, the nanofilm will bend. On the other hand, surface stress and surface elasticity imbalances induce a nanofilm to curl into a nanotube when the nanofilm is very thin. The surface stress and surface elasticity balances induce uniform in-plane strain (the overall film relaxation), while the vertical direction of the nanofilm relaxes reversely due to Poisson’s effect. And then, the crystal lattice constants of in-plane and vertical directions are different from each other, the ratio of these two lattice constants decrease with film thickness increase. Hence, the symmetry of the nanofilm is lowered by the overall film relaxation.
The Effect of Talker and Listener Depressive Symptoms on Speech Intelligibility
Authors: Yi Hoyoung , Smiljanic Rajka , Chandrasekaran Bharath 
Published: November 2019

Purpose
This study examined the effect of depressive symptoms on production and perception of conversational and clear speech (CS) sentences.

Method
Five talkers each with high-depressive (HD) and low-depressive (LD) symptoms read sentences in conversational and clear speaking style. Acoustic measures of speaking rate, mean fundamental frequency (F0; Hz), F0 range (Hz), and energy in the 1–3 kHz range (dB) were obtained. Thirty-two young adult participants (15 HD, 16 LD) heard these conversational and clear sentences mixed with energetic masking (speech-shaped noise) at −5 dB SPL signal-to-noise ratio. Another group of 39 young adult participants (18 HD, 19 LD) heard the same sentences mixed with informational masking (one-talker competing speech) at −12 dB SPL signal-to-noise ratio. The key word correct score was obtained.

Results
CS was characterized by a decreased speaking rate, increased F0 mean and range, and increased energy in the 1–3 kHz range. Talkers with HD symptoms produced these modifications significantly less compared to talkers with LD symptoms. When listening to speech in energetic masking (speech-shaped noise), listeners with both HD and LD symptoms benefited less from the CS produced by HD talkers. Listeners with HD symptoms performed significantly worse than listeners with LD symptoms when listening to speech in informational masking (one-talker competing speech).

Conclusions
Results provide evidence that depressive symptoms impact intelligibility and have the potential to aid in clinical decision making for individuals with depression.
Clusters and mirages: cataloguing stellar aggregates in the Milky Way
Authors: Cantat-Gaudin T. , Anders F. 
Published: November 2019

Context. Many of the open clusters listed in modern catalogues were initially reported by visual astronomers as apparent overdensities of bright stars. As observational techniques and analysis methods continue to improve, some of them have been shown to be chance alignments of stars and not true clusters. Recent publications making use of Gaia DR2 data have provided membership lists for over a thousand clusters, however, many nearby objects listed in the literature have so far evaded detection.
Aims. We aim to update the Gaia DR2 cluster census by performing membership determinations for known clusters that had been missed by previous studies and for recently-discovered clusters. We investigate a sub-set of non-detected clusters that, according to their literature parameters, should be easily visible in Gaia. Confirming or disproving the existence of old, inner-disc, high-altitude clusters is especially important as their survival or disruption is linked to the dynamical processes that drive the evolution of the Milky Way.
Methods. We employed the Gaia DR2 catalogue and a membership assignment procedure, as well as visual inspections of spatial, proper motion, and parallax distributions. We used membership lists provided by other authors when available.
Results. We derived membership lists for 150 objects, including ten that were already known prior to Gaia. We compiled a final list of members for 1481 clusters. Among the objects that we are still unable to identify with the Gaia data, we argue that many (mostly putatively old, relatively nearby, high-altitude objects) are not true clusters.
Conclusions. At present, the only confirmed cluster located further than 500 pc away from the Galactic plane within the Solar circle is NGC 6791. It is likely that the objects discussed in this study only represent a fraction of the non-physical groupings erroneously listed in the catalogues as genuine open clusters and that those lists need further cleaning.