bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathomechanisms of ALS8: altered autophagy and defective RNA binding protein (RBP) homeostasis due to the VAPB P56S mutation
Authors: Tripathi Priyanka , Guo Haihong , Dreser Alice , Yamoah Alfred , Sechi Antonio , Jesse Christopher Marvin , Katona Istvan , Doukas Panagiotis , Nikolin Stefan , Ernst Sabrina , Aronica Eleonora , Glaß Hannes , Hermann Andreas , Steinbusch Harry , Feller Alfred C. , Bergmann Markus , Jaarsma Dick , Weis Joachim , Goswami Anand 
Published: May 2021

AbstractMutations in RNA binding proteins (RBPs) and in genes regulating autophagy are frequent causes of familial amyotrophic lateral sclerosis (fALS). The P56S mutation in vesicle-associated membrane protein-associated protein B (VAPB) leads to fALS (ALS8) and spinal muscular atrophy (SMA). While VAPB is primarily involved in the unfolded protein response (UPR), vesicular trafficking and in initial steps of the autophagy pathway, the effect of mutant P56S-VAPB on autophagy regulation in connection with RBP homeostasis has not been explored yet. Examining the muscle biopsy of our index ALS8 patient of European origin revealed globular accumulations of VAPB aggregates co-localised with autophagy markers LC3 and p62 in partially atrophic and atrophic muscle fibres. In line with this skin fibroblasts obtained from the same patient showed accumulation of P56S-VAPB aggregates together with LC3 and p62. Detailed investigations of autophagic flux in cell culture models revealed that P56S-VAPB alters both initial and late steps of the autophagy pathway. Accordingly, electron microscopy complemented with live cell imaging highlighted the impaired fusion of accumulated autophagosomes with lysosomes in cells expressing P56S-VAPB. Consistent with these observations, neuropathological studies of brain and spinal cord of P56S-VAPB transgenic mice revealed signs of neurodegeneration associated with altered protein quality control and defective autophagy. Autophagy and RBP homeostasis are interdependent, as demonstrated by the cytoplasmic mis-localisation of several RBPs including pTDP-43, FUS, Matrin 3 which often sequestered with P56S-VAPB aggregates both in cell culture and in the muscle biopsy of the ALS8 patient. Further confirming the notion that aggregation of the RBPs proceeds through the stress granule (SG) pathway, we found persistent G3BP- and TIAR1-positive SGs in P56S-VAPB expressing cells as well as in the ALS8 patient muscle biopsy. We conclude that P56S-VAPB-ALS8 involves a cohesive pathomechanism of aberrant RBP homeostasis together with dysfunctional autophagy.
Mutations inhibiting KDM4B drive ALT activation in ATRX-mutated glioblastomas
Authors: Udugama M. , Hii L. , Garvie A. , Cervini M. , Vinod B. , Chan F.-L. , Das P. P. , Mann J. R. , Collas P. , Voon H. P. J. , Wong L. H. 
Published: May 2021

AbstractAlternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers. ALT cancers are strongly associated with inactivating mutations in ATRX; yet loss of ATRX alone is insufficient to trigger ALT, suggesting that additional cooperating factors are involved. We identify H3.3G34R and IDH1/2 mutations as two such factors in ATRX-mutated glioblastomas. Both mutations are capable of inactivating histone demethylases, and we identify KDM4B as the key demethylase inactivated in ALT. Mouse embryonic stem cells inactivated for ATRX, TP53, TERT and KDM4B (KDM4B knockout or H3.3G34R) show characteristic features of ALT. Conversely, KDM4B over-expression in ALT cancer cells abrogates ALT-associated features. In this work, we demonstrate that inactivation of KDM4B, through H3.3G34R or IDH1/2 mutations, acts in tandem with ATRX mutations to promote ALT in glioblastomas.
Systematic inference and comparison of multi-scale chromatin sub-compartments connects spatial organization to cell phenotypes
Authors: Liu Yuanlong , Nanni Luca , Sungalee Stephanie , Zufferey Marie , Tavernari Daniele , Mina Marco , Ceri Stefano , Oricchio Elisa , Ciriello Giovanni 
Published: May 2021

AbstractChromatin compartmentalization reflects biological activity. However, inference of chromatin sub-compartments and compartment domains from chromosome conformation capture (Hi-C) experiments is limited by data resolution. As a result, these have been characterized only in a few cell types and systematic comparisons across multiple tissues and conditions are missing. Here, we present Calder, an algorithmic approach that enables the identification of multi-scale sub-compartments at variable data resolution. Calder allows to infer and compare chromatin sub-compartments and compartment domains in >100 cell lines. Our results reveal sub-compartments enriched for poised chromatin states and undergoing spatial repositioning during lineage differentiation and oncogenic transformation.
Discontinuous epidemic transition due to limited testing
Authors: Scarselli Davide , Budanur Nazmi Burak , Timme Marc , Hof Björn 
Published: May 2021

AbstractHigh impact epidemics constitute one of the largest threats humanity is facing in the 21st century. In the absence of pharmaceutical interventions, physical distancing together with testing, contact tracing and quarantining are crucial in slowing down epidemic dynamics. Yet, here we show that if testing capacities are limited, containment may fail dramatically because such combined countermeasures drastically change the rules of the epidemic transition: Instead of continuous, the response to countermeasures becomes discontinuous. Rather than following the conventional exponential growth, the outbreak that is initially strongly suppressed eventually accelerates and scales faster than exponential during an explosive growth period. As a consequence, containment measures either suffice to stop the outbreak at low total case numbers or fail catastrophically if marginally too weak, thus implying large uncertainties in reliably estimating overall epidemic dynamics, both during initial phases and during second wave scenarios.
Emerging concepts in intestinal immune control of obesity-related metabolic disease
Authors: Khan Saad , Luck Helen , Winer Shawn , Winer Daniel A. 
Published: May 2021

AbstractThe intestinal immune system is an important modulator of glucose homeostasis and obesity-associated insulin resistance. Dietary factors, the intestinal microbiota and their metabolites shape intestinal immunity during obesity. The intestinal immune system in turn affects processes such as intestinal permeability, immune cell trafficking, and intestinal hormone availability, impacting systemic insulin resistance. Understanding these pathways might identify mechanisms underlying treatments for insulin resistance, such as metformin and bariatric surgery, or aid in developing new therapies and vaccination approaches. Here, we highlight evolving concepts centered on intestinal immunity, diet, and the microbiota to provide a working model of obesity-related metabolic disease.
Magnetization control by angular momentum transfer from surface acoustic wave to ferromagnetic spin moments
Authors: Sasaki R. , Nii Y. , Onose Y. 
Published: May 2021

AbstractInterconversion between electron spin and other forms of angular momentum is useful for spin-based information processing. Well-studied examples of this are the conversion of photon angular momentum and rotation into ferromagnetic moment. Recently, several theoretical studies have suggested that the circular vibration of atoms work as phonon angular momentum; however, conversion between phonon angular momentum and spin-moment has yet to be demonstrated. Here, we demonstrate that the phonon angular momentum of surface acoustic wave can control the magnetization of a ferromagnetic Ni film by means of the phononic-to-electronic conversion of angular momentum in a Ni/LiNbO3 hybrid device. The result clearly shows that the phonon angular momentum is useful for increasing the functionality of spintronic devices.
Breathing-driven prefrontal oscillations regulate maintenance of conditioned-fear evoked freezing independently of initiation
Authors: Bagur Sophie , Lefort Julie M. , Lacroix Marie M. , de Lavilléon Gaëtan , Herry Cyril , Chouvaeff Mathilde , Billand Clara , Geoffroy Hélène , Benchenane Karim 
Published: May 2021

AbstractBrain–body interactions are thought to be essential in emotions but their physiological basis remains poorly understood. In mice, regular 4 Hz breathing appears during freezing after cue-fear conditioning. Here we show that the olfactory bulb (OB) transmits this rhythm to the dorsomedial prefrontal cortex (dmPFC) where it organizes neural activity. Reduction of the respiratory-related 4 Hz oscillation, via bulbectomy or optogenetic perturbation of the OB, reduces freezing. Behavioural modelling shows that this is due to a specific reduction in freezing maintenance without impacting its initiation, thus dissociating these two phenomena. dmPFC LFP and firing patterns support the region’s specific function in freezing maintenance. In particular, population analysis reveals that network activity tracks 4 Hz power dynamics during freezing and reaches a stable state at 4 Hz peak that lasts until freezing termination. These results provide a potential mechanism and a functional role for bodily feedback in emotions and therefore shed light on the historical James–Cannon debate.
Oriented arrangement of simple monomers enabled by confinement: towards living supramolecular polymerization
Authors: Zong Yingtong , Xu Si-Min , Shi Wenying , Lu Chao 
Published: May 2021

AbstractThe living supramolecular polymerization technique provides an exciting research avenue. However, in comparison with the thermodynamic spontaneous nucleation, using simple monomers to realize living supramolecular polymerization is hardly possible from an energy principle. This is because the activation barrier of kinetically trapped simple monomer (nucleation step) is insufficiently high to control the kinetics of subsequent elongation. Here, with the benefit of the confinement from the layered double hydroxide (LDH) nanomaterial, various simple monomers, (such as benzene, naphthalene and pyrene derivatives) successfully form living supramolecular polymer (LSP) with length control and narrow dispersity. The degree of polymerization can reach ~6000. Kinetics studies reveal LDH overcomes a huge energy barrier to inhibit undesired spontaneous nucleation of monomers and disassembly of metastable states. The universality of this strategy will usher exploration into other multifunctional molecules and promote the development of functional LSP.
Deforestation reduces rainfall and agricultural revenues in the Brazilian Amazon
Authors: Leite-Filho Argemiro Teixeira , Soares-Filho Britaldo Silveira , Davis Juliana Leroy , Abrahão Gabriel Medeiros , Börner Jan 
Published: May 2021

AbstractIt has been suggested that rainfall in the Amazon decreases if forest loss exceeds some threshold, but the specific value of this threshold remains uncertain. Here, we investigate the relationship between historical deforestation and rainfall at different geographical scales across the Southern Brazilian Amazon (SBA). We also assess impacts of deforestation policy scenarios on the region’s agriculture. Forest loss of up to 55–60% within 28 km grid cells enhances rainfall, but further deforestation reduces rainfall precipitously. This threshold is lower at larger scales (45–50% at 56 km and 25–30% at 112 km grid cells), while rainfall decreases linearly within 224 km grid cells. Widespread deforestation results in a hydrological and economic negative-sum game, because lower rainfall and agricultural productivity at larger scales outdo local gains. Under a weak governance scenario, SBA may lose 56% of its forests by 2050. Reducing deforestation prevents agricultural losses in SBA up to US$ 1 billion annually.
A rich catalog of C–C bonded species formed in CO2 reduction on a plasmonic photocatalyst
Authors: Devasia Dinumol , Wilson Andrew J. , Heo Jaeyoung , Mohan Varun , Jain Prashant K. 
Published: May 2021

AbstractThe understanding and rational design of heterogeneous catalysts for complex reactions, such as CO2 reduction, requires knowledge of elementary steps and chemical species prevalent on the catalyst surface under operating conditions. Using in situ nanoscale surface-enhanced Raman scattering, we probe the surface of a Ag nanoparticle during plasmon-excitation-driven CO2 reduction in water. Enabled by the high spatiotemporal resolution and surface sensitivity of our method, we detect a rich array of C1–C4 species formed on the photocatalytically active surface. The abundance of multi-carbon compounds, such as butanol, suggests the favorability of kinetically challenging C–C coupling on the photoexcited Ag surface. Another advance of this work is the use of isotope labeling in nanoscale probing, which allows confirmation that detected species are the intermediates and products of the catalytic reaction rather than spurious contaminants. The surface chemical knowledge made accessible by our approach will inform the modeling and engineering of catalysts.
Overtemperature-protection intelligent molecular chiroptical photoswitches
Authors: Yao Jiabin , Wu Wanhua , Xiao Chao , Su Dan , Zhong Zhihui , Mori Tadashi , Yang Cheng 
Published: May 2021

AbstractStimuli-responsive intelligent molecular machines/devices are of current research interest due to their potential application in minimized devices. Constructing molecular machines/devices capable of accomplishing complex missions is challenging, demanding coalescence of various functions into one molecule. Here we report the construction of intelligent molecular chiroptical photoswitches based on azobenzene-fused bicyclic pillar[n]arene derivatives, which we defined as molecular universal joints (MUJs). The Z/E photoisomerization of the azobenzene moiety of MUJs induces rolling in/out conformational switching of the azobenzene-bearing side-ring and consequently leads to planar chirality switching of MUJs. Meanwhile, temperature variation was demonstrated to also cause conformational/chiroptical inversion due to the significant entropy change during the ring-flipping. As a result, photo-induced chiroptical switching could be prohibited when the temperature exceeded an upper limit, demonstrating an intelligent molecular photoswitch having over-temperature protection function, which is in stark contrast to the low-temperature-gating effect commonly encountered.
Outpatient prescribing pattern for acute bronchitis in primary healthcare settings in China
Authors: Fu Mengyuan , Wushouer Haishaerjiang , Hu Lin , Li Nan , Guan Xiaodong , Shi Luwen , Ross-Degnan Dennis 
Published: May 2021

AbstractInappropriate prescribing for acute bronchitis in primary healthcare settings (PHSs) is commonly seen worldwide. Here we describe the prescribing patterns and antibiotic use for acute bronchitis in PHSs across China. We conduct a nationwide cross-sectional survey to collect outpatient prescriptions from PHSs in 2017. Patients diagnosed with acute bronchitis without other infections are eligible for this study. Generalized estimating equations are used for analysis. Overall, 10,678 prescriptions for acute bronchitis from 214 institutions are included. The antibiotic prescription rate is 44.5% for total prescriptions, and differs significantly by region and urban/rural status (p < 0.05). Among all single-antibiotic prescriptions, 91.5% are broad-spectrum. Two-thirds of the prescriptions contain medicines for symptom management. The overall guideline compliance rate of acute bronchitis treatment for adults is 31.0%. Prescribing antibiotics, especially broad-spectrum ones, for acute bronchitis is commonly observed in Chinese PHSs. Targeted interventions are urgently needed for Chinese primary clinicians, especially in western rural areas.
Vibratory behaviour produces different vibration patterns in presence of reproductives in a subterranean termite species
Authors: Pailler Louis , Desvignes Samuel , Ruhland Fanny , Pineirua Miguel , Lucas Christophe 
Published: May 2021

AbstractVibratory behaviours are widespread in social insects, but the produced vibrations remain poorly explored. Communication using vibrations is an efficient way to transmit information in subterranean environments where visual and odorant signals are less efficient. In termites, different vibratory behaviours are performed in different contexts like reproductive regulation and alarm signalling, but only few studies explored the structure of the produced vibrations (i.e., duration, number of pulses, amplitude). Here, we described several types of vibrations produced by a vibratory behaviour widespread in termites (body-shaking), which can be transmitted through the substrate and detected by other colony members. We analysed the structures of the emitted vibrations and the occurrence of the body-shaking events in presence/absence of reproductives and/or in presence/absence of a stress stimuli (flashlight) in the subterranean termiteReticulitermes flavipes. Interestingly, only the presence of the reproductives did influence the number of pulses and the duration of the emitted vibrations. Moreover, the first part of the emitted vibrations seems to be enough to encode reproductive information, but other parts might hold other type of information. Body-shaking occurrence did increase in presence of reproductives but only briefly under a flashlight. These results show that vibratory cues are complex in termites and their diversity might encode a plurality of social cues.
Markedly poor physical functioning status of people experiencing homelessness admitted to an acute hospital setting
Authors: Kiernan S. , Ní Cheallaigh C. , Murphy N. , Dowds J. , Broderick J. 
Published: May 2021

AbstractAdults who are homeless experience poor health and frequently require hospital in-patient care but the physical functioning ability of this group is rarely considered. The objective of this study was to evaluate a broad range of physical functioning variables to enable better future planning of targeted health and accommodation services for this group. This cross-sectional, observational study was conducted in a large acute hospital in Dublin, Ireland. A comprehensive ward-based test battery evaluated physical functioning in 65 in-patients registered as homeless with an age range of 23–80 years. Less than 10% (n = 5) were > 70 years. 58/65 (83%) of participants had mobility limitations and 35/65 (54%) reported at least one fall in the previous six months. Only 25/66 (35%) were able to walk for 6 min and 20/65 (31%) were able to climb one flight of stairs. 45/63 (70%) of participants were pre-frail or frail. Muscular mass was normal in the majority of participants but grip strength was low. This study revealed hospital in-patients registered as homeless displayed particularly poor physical functioning levels and mobility regardless of age. Health and housing services should address the unmet physical functioning needs of this vulnerable group.
Salivary caffeine in Parkinson’s disease
Authors: Leodori Giorgio , De Bartolo Maria Ilenia , Belvisi Daniele , Ciogli Alessia , Fabbrini Andrea , Costanzo Matteo , Manetto Simone , Conte Antonella , Villani Claudio , Fabbrini Giovanni , Berardelli Alfredo 
Published: May 2021

AbstractWe aimed to investigate salivary caffeine content, caffeine absorption and metabolism in Parkinson’s disease (PD) and verify whether salivary caffeine can be used as a biomarker of PD. We enrolled 98 PD patients and 92 healthy subjects. Caffeine and its major metabolite, paraxanthine, were measured in saliva samples collected before and 4 h after the oral intake of caffeine (100 mg). We measured caffeine absorption as the normalized increase in caffeine levels, and caffeine metabolism as the paraxanthine/caffeine ratio. The Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the Hoehn & Yahr, the presence of motor complications, and levodopa equivalent dose (LED) were assessed and correlated with caffeine levels, absorption, and metabolism. The effects of demographic and environmental features possibly influencing caffeine levels were also investigated. Caffeine levels were decreased in patients with moderate/advanced PD, while caffeine levels were normal in patients with early and de-novo PD, unrelated to caffeine intake. Caffeine absorption and metabolism were normal in PD. Decreased salivary caffeine levels in PD were associated with higher disease severity, longer duration, and the presence of motor complications, no significant association was found with LED. Salivary caffeine decrease correlates with PD progression.
Effects of cadmium stress on growth and physiological characteristics of sassafras seedlings
Authors: Zhao Hongyi , Guan Juelan , Liang Qing , Zhang Xueyuan , Hu Hongling , Zhang Jian 
Published: May 2021

AbstractThe effects of cadmium stress on the growth and physiological characteristics of Sassafras tzumu Hemsl. were studied in pot experiments. Five Cd levels were tested [CT(Control Treatment) : 0 mg/kg, Cd5: 5 mg/kg, Cd20: 20 mg/kg, Cd50: 50 mg/kg, and Cd100: 100 mg/kg]. The growth and physiological characteristics of the sassafras seedlings in each level were measured. The results showed that soil Cd had negative influences on sassafras growth and reduced the net growth of plant height and the biomass of leaf, branch and root. Significant reductions were recorded in root biomass by 18.18%(Cd5), 27.35%(Cd20), 27.57%(Cd50) and 28.95%(Cd100). The contents of hydrogen peroxide decreased first then increased while malondialdehyde showed the opposite trend with increasing cadmium concentration. Decreases were found in hydrogen peroxide contents by 10.96%(Cd5), 11.82%(Cd20) and 7.02%(Cd50); increases were found in malondialdehyde contents by 15.47%(Cd5), 16.07%(Cd20) and 7.85%(Cd50), indicating that cadmium stress had a certain effect on the peroxidation of the inner cell membranes in the seedlings that resulted in damage to the cell membrane structure. Superoxide dismutase activity decreased among treatments by 17.05%(Cd5), 10,68%(Cd20), 20.85%(Cd50) and 8.91%(Cd100), while peroxidase activity increased steadily with increasing cadmium concentration; these results suggest that peroxidase is likely the main protective enzyme involved in the reactive oxygen removal system in sassafras seedlings. Upward trends were observed in proline content by 90.76%(Cd5), 74.36%(Cd20), 99.73%(Cd50) and 126.01%(Cd100). The increase in proline content with increasing cadmium concentration indicated that cadmium stress induced proline synthesis to resist osmotic stress in the seedlings. Compared to that in CT, the soluble sugar content declined under the different treatments by 32.84%(Cd5), 5.85%(Cd20), 25.55%(Cd50) and 38.69%(Cd100). Increases were observed in the soluble protein content by 2.34%(Cd5), 21.36%(Cd20), 53.15%(Cd50) and 24.22%(Cd100). At different levels of cadmium stress, the chlorophyll content in the seedlings first increased and then decreased, and it was higher in the Cd5 and Cd20 treatments than that in the CT treatment. These results reflected that cadmium had photosynthesis-promoting effects at low concentrations and photosynthesis-suppressing effects at high concentrations. The photosynthetic gas exchange parameters and photosynthetic light-response parameters showed downward trends with increasing cadmium concentration compared with those in CT; these results reflected the negative effects of cadmium stress on photosynthesis in sassafras seedlings.