bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure and dynamics of an α-fucosidase reveal a mechanism for highly efficient IgG transfucosylation
Authors: Klontz Erik H. , Li Chao , Kihn Kyle , Fields James K. , Beckett Dorothy , Snyder Greg A. , Wintrode Patrick L. , Deredge Daniel , Wang Lai-Xi , Sundberg Eric J.
Published: December 2020

Fucosylation is important for the function of many proteins with biotechnical and medical applications. Alpha-fucosidases comprise a large enzyme family that recognizes fucosylated substrates with diverse α-linkages on these proteins.Lactobacillus caseiproduces an α-fucosidase, called AlfC, with specificity towards α(1,6)-fucose, the only linkage found in humanN-glycan core fucosylation. AlfC and certain point mutants thereof have been used to add and remove fucose from monoclonal antibodyN-glycans, with significant impacts on their effector functions. Despite the potential uses for AlfC, little is known about its mechanism. Here, we present crystal structures of AlfC, combined with mutational and kinetic analyses, hydrogen–deuterium exchange mass spectrometry, molecular dynamic simulations, and transfucosylation experiments to define the molecular mechanisms of the activities of AlfC and its transfucosidase mutants. Our results indicate that AlfC creates an aromatic subsite adjacent to the active site that specifically accommodates GlcNAc in α(1,6)-linkages, suggest that enzymatic activity is controlled by distinct open and closed conformations of an active-site loop, with certain mutations shifting the equilibrium towards open conformations to promote transfucosylation over hydrolysis, and provide a potentially generalizable framework for the rational creation of AlfC transfucosidase mutants.
Heat Shock Factor 1-dependent extracellular matrix remodeling mediates the transition from chronic intestinal inflammation to colon cancer
Authors: Levi-Galibov Oshrat , Lavon Hagar , Wassermann-Dozorets Rina , Pevsner-Fischer Meirav , Mayer Shimrit , Wershof Esther , Stein Yaniv , Brown Lauren E. , Zhang Wenhan , Friedman Gil , Nevo Reinat , Golani Ofra , Katz Lior H. , Yaeger Rona , Laish Ido , Porco John A. , Sahai Erik , Shouval Dror S. , Kelsen David , Scherz-Shouval Ruth
Published: December 2020

In the colon, long-term exposure to chronic inflammation drives colitis-associated colon cancer (CAC) in patients with inflammatory bowel disease. While the causal and clinical links are well established, molecular understanding of how chronic inflammation leads to the development of colon cancer is lacking. Here we deconstruct the evolving microenvironment of CAC by measuring proteomic changes and extracellular matrix (ECM) organization over time in a mouse model of CAC. We detect early changes in ECM structure and composition, and report a crucial role for the transcriptional regulator heat shock factor 1 (HSF1) in orchestrating these events. Loss of HSF1 abrogates ECM assembly by colon fibroblasts in cell-culture, prevents inflammation-induced ECM remodeling in mice and inhibits progression to CAC. Establishing relevance to human disease, we find high activation of stromal HSF1 in CAC patients, and detect the HSF1-dependent proteomic ECM signature in human colorectal cancer. Thus, HSF1-dependent ECM remodeling plays a crucial role in mediating inflammation-driven colon cancer.
Benzene- and pyridine-incorporated octaphyrins with different coordination modes toward two PdII centers
Authors: Liu Le , Hu Zhiwen , Zhang Fenni , Liu Yang , Xu Ling , Zhou Mingbo , Tanaka Takayuki , Osuka Atsuhiro , Song Jianxin
Published: December 2020

Expanded porphyrins have received considerable attention due to their unique optical, electrochemical and coordination properties. Here, we report benzene- and pyridine-incorporated octaphyrins(1.1.0.0.1.1.0.0), which are synthesized through Suzuki-Miyaura coupling of α,α′-diboryltripyrrane with m-dibromobenzene and 2,6-dibromopyridine, respectively, and subsequent oxidation with 2,3-dicyano-5,6-dichlorobenzoquinone. Both octaphyrins are nonaromatic and take on dumbbell structures. Upon treatment with Pd(OOCCH3)2, the benzene-incorporated one gives a Ci symmetric NNNC coordinated bis-PdII complex but the pyridine incorporated one gives Ci and Cs symmetric NNNC coordinated bis-PdII complexes along with an NNNN coordinated bis-PdII complex bearing a transannular C–C bond between the pyrrole α-positions. In addition, these two pyridine-containing NNNC PdII complexes undergo trifluoroacetic acid-induced clean interconversion.
Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells
Authors: Tremblay Cedric S. , Chiu Sung Kai , Saw Jesslyn , McCalmont Hannah , Litalien Veronique , Boyle Jacqueline , Sonderegger Stefan E. , Chau Ngoc , Evans Kathryn , Cerruti Loretta , Salmon Jessica M. , McCluskey Adam , Lock Richard B. , Robinson Phillip J. , Jane Stephen M. , Curtis David J.
Published: December 2020

Intensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance.
Morphological evolution of Pt-modified nanoporous gold after thermal coarsening in reductive and oxidative environments
Authors: El-Zoka A. A. , Langelier B. , Botton G. A. , Newman R. C.
Published: December 2020

Nanoporous gold made by dealloying AgAuPt (NPG-Pt) has been shown to exhibit several interesting catalytic properties, tied to its exceptionally high surface area; however, structural degradation may occur owing to thermal coarsening. To understand the effect of atmosphere chemistry on thermal coarsening and degradation, and means of limiting it, this study focuses on the high-resolution characterization of NPG-Pt layers coarsened in reductive Ar-H2 atmosphere, and in oxidative air. Atom probe tomography (APT) analysis is performed on NPG-Pt, coarsened separately in either Ar-H2 or air, to characterize the atomic-scale chemical changes in the nanoligaments and to develop a mechanistic view of the inherent processes. A tendency of Ag to segregate to the surface during coarsening is found to lead to complete elimination of the nanoligament core-shell structures in both cases. Large Pt segregates form during coarsening in Ar-H2, but under the surface of the ligaments, having relatively little effect on the coarsening rate. The oxygen-induced segregation of Pt was observed to cause the inhibition of thermal coarsening after minor loss in surface area-to-volume ratio. Findings in this paper help in understanding further the thermal coarsening of heterogeneous nanomaterials made by dealloying, and the pertinent factors that come into play in different chemical environments.
Cerebrospinal fluid glutamate changes in functional movement disorders
Authors: Demartini Benedetta , Invernizzi Roberto William , Campiglio Laura , Bocci Tommaso , D’Arrigo Andrea , Arighi Andrea , Sciacca Francesca , Galimberti Daniela , Scarpini Elio , Gambini Orsola , Priori Alberto
Published: December 2020

The aim of this study was to assess cerebrospinal fluid (CSF) concentrations of specific amino acids using a high-performance liquid chromatography system in a sample of patients with functional movement disorders (FMDs) and in a sample of controls. CSF levels of glutamate were significantly lower in patients with FMD than in controls. This finding argues in favor of glutamatergic dysfunction in the pathophysiology of FMD.
Verification of a resetting protocol for an uncontrolled superconducting qubit
Authors: Gong Ming , Xu Feihu , Li Zheng-Da , Wang Zizhu , Zhang Yu-Zhe , Wu Yulin , Li Shaowei , Zhao Youwei , Wang Shiyu , Zha Chen , Deng Hui , Yan Zhiguang , Rong Hao , Liang Futian , Lin Jin , Xu Yu , Guo Cheng , Sun Lihua , Clark Juno , Peng Cheng-Zhi , Chen Yu-Ao , Zhu Xiaobo , Pan Jian-Wei
Published: December 2020

Quantum resetting protocols allow a quantum system to be sent to a state in the past by making it interact with quantum probes when neither the free evolution of the system nor the interaction is controlled. We experimentally verify the simplest non-trivial case of a quantum resetting protocol, known as the

$${{\mathcal{W}}}_{4}$$

W

4

protocol, with five superconducting qubits, testing it with different types of free evolutions and target–probe interactions. After projection, we obtained a reset state fidelity as high as 0.951, and the process fidelity was found to be 0.792. We also implemented 100 randomly chosen interactions and demonstrated an average success probability of 0.323 for

$$\left|1\right\rangle$$

1

and 0.292 for

$$\left|-\right\rangle$$

−

, and experimentally confirmed the nonzero probability of success for unknown interactions; the numerical simulated values are about 0.3. Our experiment shows that the simplest quantum resetting protocol can be implemented with current technologies, making such protocols a valuable tool in the eternal fight against unwanted evolution in quantum systems.
MnBi2Te4-family intrinsic magnetic topological materials
Authors: He Ke
Published: December 2020

MnBi2Te4 and its derivative compounds have received focused research interests recently for their inherent magnetic order and the rich, robust and tunable topological phases hosted in them. Here, I briefly introduce MnBi2Te4-family intrinsic magnetic topological materials—the electronic and magnetic properties, the topological phase diagrams and the research progress made on them in the past years. I try to present a simple picture to understand their rich electronic, magnetic and topological properties, and a concise guide to engineer them for intended topological phases and the quantum anomalous Hall effect at higher temperature.
ClimateEU, scale-free climate normals, historical time series, and future projections for Europe
Authors: Marchi Maurizio , Castellanos-Acuña Dante , Hamann Andreas , Wang Tongli , Ray Duncan , Menzel Annette
Published: December 2020

Interpolated climate data have become essential for regional or local climate change impact assessments and the development of climate change adaptation strategies. Here, we contribute an accessible, comprehensive database of interpolated climate data for Europe that includes monthly, annual, decadal, and 30-year normal climate data for the last 119 years (1901 to 2019) as well as multi-model CMIP5 climate change projections for the 21st century. The database also includes variables relevant for ecological research and infrastructure planning, comprising more than 20,000 climate grids that can be queried with a provided ClimateEU software package. In addition, 1 km and 2.5 km resolution gridded data generated by the software are available for download. The quality of ClimateEU estimates was evaluated against weather station data for a representative subset of climate variables. Dynamic environmental lapse rate algorithms employed by the software to generate scale-free climate variables for specific locations lead to improvements of 10 to 50% in accuracy compared to gridded data. We conclude with a discussion of applications and limitations of this database.
Altered regional homogeneity and functional brain networks in Type 2 diabetes with and without mild cognitive impairment
Authors: Xiong Ying , Chen Xiaodan , Zhao Xu , Fan Yang , Zhang Qiang , Zhu Wenzhen
Published: December 2020

Patients with Type-2 Diabetes Mellitus (T2DM) have a considerably higher risk of developing mild cognitive impairment (MCI) and dementia. The initial symptoms are very insidious at onset. We investigated the alterations in spontaneous brain activity and network connectivity through regional homogeneity (ReHo) and graph theoretical network analyses, respectively, of resting-state functional Magnetic Resonance Imaging (rs-fMRI) in T2DM patients with and without MCI, so as to facilitate early diagnose. Twenty-five T2DM patients with MCI (DM-MCI), 25 T2DM patients with normal cognition (DM-NC), 27 healthy controls were enrolled. Whole-brain ReHo values were calculated and topological properties of functional networks were analyzed. The DM-MCI group exhibited decreased ReHo in the left inferior/middle occipital gyrus and right inferior temporal gyrus, and increased ReHo in frontal gyrus compared to the DM-NCs. Significant correlations were found between ReHo values and clinical measurements. The DM-MCI group illustrated greater clustering coefficient/local efficiency and altered nodal characteristics (efficiency, degree and betweenness), which increased in certain occipital, temporal and parietal regions but decreased in the right inferior temporal gyrus, compared to the DM-NCs. The altered ReHo and impaired network organization may underlie the impaired cognitive functions in T2DM and suggesting a compensation mechanism. These rs-fMRI measures have the potential as biomarkers of disease progression in diabetic encephalopathy.
Deciphering the mechanoresponsive role of β-catenin in keratoconus epithelium
Authors: Amit Chatterjee , Padmanabhan Prema , Narayanan Janakiraman
Published: December 2020

Keratoconus (KC) is a corneal dystrophy characterized by progressive ectasia that leads to severe visual impairment and remains one of the leading indications for corneal transplantation. The etiology is believed to be multifactorial and alterations have been documented in the biomechanical, biochemical and ultrastructural characteristics of the cornea. While the exact site of disease origin is still debated, changes in the corneal epithelium are believed to occur even before the disease is clinically manifested. In this study we investigate the possible role of β-catenin as mechanotransducer in KC corneal epithelium. The sheets of corneal epithelium removed from keratoconic eyes when they underwent collagen crosslinking as a therapeutic procedure were used for this study. The healthy corneal epithelium of patients undergoing Laser Refractive Surgery for the correction of their refractive error, served as controls. Immunoblotting and tissue immunofluorescence studies were performed on KC epithelium to analyse the expression and localization of β-catenin, E-cadherin, ZO1, α-catenin, Cyclin D1, α-actinin, RhoA, and Rac123. Co-immunoprecipitation of β-catenin followed by mass spectrometry of KC epithelium was performed to identify its interacting partners. This was further validated by using epithelial tissues grown on scaffolds of different stiffness. Histology data reported breaks in the Bowman’s layer in KC patients. We hypothesize that these breaks expose the epithelium to the keratoconic corneal stroma, which, is known to have a decreased elastic modulus and that β-catenin acts as a mechanotransducer that induces structural changes such as loss of polarity (Syntaxin3) and barrier function (ZO1) through membrane delocalization. The results of our study strongly suggest that β-catenin could be a putative mechanotransducer in KC epithelium, thus supporting our hypothesis.
Multiscale classification of heart failure phenotypes by unsupervised clustering of unstructured electronic medical record data
Authors: Nagamine Tasha , Gillette Brian , Pakhomov Alexey , Kahoun John , Mayer Hannah , Burghaus Rolf , Lippert Jörg , Saxena Mayur
Published: December 2020

As a leading cause of death and morbidity, heart failure (HF) is responsible for a large portion of healthcare and disability costs worldwide. Current approaches to define specific HF subpopulations may fail to account for the diversity of etiologies, comorbidities, and factors driving disease progression, and therefore have limited value for clinical decision making and development of novel therapies. Here we present a novel and data-driven approach to understand and characterize the real-world manifestation of HF by clustering disease and symptom-related clinical concepts (complaints) captured from unstructured electronic health record clinical notes. We used natural language processing to construct vectorized representations of patient complaints followed by clustering to group HF patients by similarity of complaint vectors. We then identified complaints that were significantly enriched within each cluster using statistical testing. Breaking the HF population into groups of similar patients revealed a clinically interpretable hierarchy of subgroups characterized by similar HF manifestation. Importantly, our methodology revealed well-known etiologies, risk factors, and comorbid conditions of HF (including ischemic heart disease, aortic valve disease, atrial fibrillation, congenital heart disease, various cardiomyopathies, obesity, hypertension, diabetes, and chronic kidney disease) and yielded additional insights into the details of each HF subgroup’s clinical manifestation of HF. Our approach is entirely hypothesis free and can therefore be readily applied for discovery of novel insights in alternative diseases or patient populations.
COG5 variants lead to complex early onset retinal degeneration, upregulation of PERK and DNA damage
Authors: Tabbarah Sami , Tavares Erika , Charish Jason , Vincent Ajoy , Paterson Andrew , Di Scipio Matteo , Yin Yue , Mendoza-Londono Roberto , Maynes Jason , Heon Elise , Monnier Philippe P.
Published: December 2020

Leber congenital amaurosis (LCA), a form of autosomal recessive severe early-onset retinal degeneration, is an important cause of childhood blindness. This may be associated with systemic features or not. Here we identified COG5 compound-heterozygous variants in patients affected with a complex LCA phenotype associated with microcephaly and skeletal dysplasia. COG5 is a component of the COG complex, which facilitates retrograde Golgi trafficking; if disrupted this can result in protein misfolding. To date, variants in COG5 have been associated with a distinct congenital disorder of glycosylation (type IIi) and with a variant of Friedreich’s ataxia. We show that COG5 variants can also result in fragmentation of the Golgi apparatus and upregulation of the UPR modulator, PKR-like endoplasmic reticulum kinase (PERK). In addition, upregulation of PERK induces DNA damage in cultured cells and in murine retina. This study identifies a novel role for COG5 in maintaining ER protein homeostasis and that disruption of that role results in activation of PERK and early-onset retinal degeneration, microcephaly and skeletal dysplasia. These results also highlight the importance of the UPR pathway in early-onset retinal dystrophy and as potential therapeutic targets for patients.
Increased incarceration rates drive growing tuberculosis burden in prisons and jeopardize overall tuberculosis control in Paraguay
Authors: Sequera Víctor Guillermo , Aguirre Sarita , Estigarribia Gladys , Cellamare Matteo , Croda Julio , Andrews Jason R. , Martinez Leonardo , García-Basteiro Alberto L.
Published: December 2020

Incarcerated populations are at high-risk to develop tuberculosis (TB), however their impact on the population-level tuberculosis epidemic has been scarcely studied. We aimed to describe the burden and trends of TB among incarcerated populations over time in Paraguay, its clinical and epidemiological differences and the population attributable fraction. This is an observational, descriptive study including all TB cases notified to the National TB control Program in Paraguay during the period 2009–2018. We also used case registries of prisoners diagnosed with tuberculosis from the Minister of Justice. The population attributable fraction of TB in the community due to incarcerated cases was estimated through Levin’s formula. The characteristics of TB cases in and outside of prison were compared as well as the characteristics of TB in prisons were modified over time. During 2009–2018, 2764 (9.7%) of the 28,534 TB reported cases in Paraguay occurred in prisons. The number of prisoners in Paraguay increased from 6258 in 2009 to 14,627 in 2018 (incarceration rate, 101 to 207 per 100,000 persons) while the number of TB cases among prisoners increased by 250% (n = 192 in 2009 versus n = 480 in 2018). The annual TB notification rate among male prisoners was 3218 and 3459 per 100,000 inmates in 2009 and 2018, respectively. The percentage of all TB cases occurring among prisoners increased from 7.1% in 2009 to 14.5% in 2018. The relative risk of TB in prisons compared to community was 70.3 (95% CI, 67.7–73.1); the overall population attributable risk was 9.5%. Among the 16 penitentiary centers in the country, two of them—Tacumbú (39.0%) and Ciudad del Este (23.3%)—represent two thirds of all TB cases in prisons. TB among inmates is predominantly concentrated in those 20–34 years old (77.3% of all), twice the percentage of cases for the same age group outside of prison. Our findings show that the TB epidemic in prisons represents one of the most important challenges for TB control in Paraguay, especially in the country’s largest cities. Appropriate TB control measures among incarcerated populations are needed and may have substantial impact on the overall TB burden in the country.
Dynamic response of cerebral blood flow to insulin-induced hypoglycemia
Authors: McManus Ruth , Ioussoufovitch Seva , Froats Elizabeth , St Lawrence Keith , Van Uum Stan , Diop Mamadou
Published: December 2020

The dynamics of cerebral blood flow (CBF) at the onset of hypoglycemia may play a key role in hypoglycemia unawareness; however, there is currently a paucity of techniques that can monitor adult CBF with high temporal resolution. Herein, we investigated the use of diffuse correlation spectroscopy (DCS) to monitor the dynamics of CBF during insulin-induced hypoglycemia in adults. Plasma glucose concentrations, cortisol levels, and changes in CBF were measured before and during hypoglycemia in 8 healthy subjects. Cerebral blood flow increased by 42% following insulin injection with a delay of 17 ± 10 min, while the onset of hypoglycemia symptoms was delayed by 24 ± 11 min. The findings suggest that the onset of CBF increments precedes the appearance of hypoglycemia symptoms in nondiabetic subjects with normal awareness to hypoglycemia, and DCS could be a valuable tool for investigating the role of CBF in hypoglycemia unawareness.
A new record for a massive Porites colony at Ta’u Island, American Samoa
Authors: Coward Georgia , Lawrence Alice , Ripley Natasha , Brown Valerie , Sudek Mareike , Brown Eric , Moffitt Ian , Fuiava Bert , Vargas-Ángel Bernardo
Published: December 2020

An exceptionally large, hermatypic colony of Porites sp. has been identified and measured at Ta’u, American Samoa. This coral was measured in November 2019 as part of an effort to catalogue all large (≥ 2 m diameter) Porites colonies around Ta’u. Colonies exceeding 10 m in diameter were recorded on three different sides of the island with seasonally different wave exposures. The largest colony measured 8 m tall, 69 m in circumference and had a diameter of 22.4 m. To date, this is the biggest colony recorded in American Samoa, and one of the largest documented worldwide. It is currently unknown why such large corals exist around this particular island. Possible explanations include mild wave or atmospheric climates and minimal anthropogenic impacts. Physiologically, these colonies may be resistant and/or resilient to disturbances. Large, intact corals can help build past (century-scale) climatic profiles, and better understand coral persistence, particularly as coral communities worldwide are declining at rapid rates.
Batesian mimicry has evolved with deleterious effects of the pleiotropic gene doublesex
Authors: Komata Shinya , Kitamura Tasuku , Fujiwara Haruhiko
Published: December 2020

Dimorphic female-limited Batesian mimicry in the swallowtail butterfly Papilio polytes is regulated by the supergene locus H, harbouring the mimetic (H) and non-mimetic (h) doublesex (dsx) gene. In the present study, we demonstrated that dsx-H negatively affects the number of eggs laid, hatching rate, larval survival rate, and adult lifespan. When crossed with hh males, the number of eggs laid of mimetic females (genotype HH) was lower than that of non-mimetic females (hh). Moreover, hh and Hh females laid fewer eggs when crossed with HH males. The hatching and larval survival rates were lower when both female and male parents harboured dsx-H. The adult lifespan of HH females was shorter than that of hh females, while it was similar in males regardless of the genotype. These findings suggest the presence of a cost–benefit balance of Batesian mimicry, which is evolved to avoid predation but is accompanied by physiological deficits, in this species.
Nitrogen isotopic signatures and fluxes of N2O in response to land-use change on naturally occurring saline–alkaline soil
Authors: Timilsina Arbindra , Dong Wenxu , Luo Jiafa , Lindsey Stuart , Wang Yuying , Hu Chunsheng
Published: December 2020

The conversion of natural grassland to semi-natural or artificial ecosystems is a large-scale land-use change (LUC) commonly occurring to saline–alkaline land. Conversion of natural to artificial ecosystems, with addition of anthropogenic nitrogen (N) fertilizer, influences N availability in the soil that may result in higher N2O emission along with depletion of 15N, while converting from natural to semi-natural the influence may be small. So, this study assesses the impact of LUC on N2O emission and 15N in N2O emitted from naturally occurring saline–alkaline soil when changing from natural grassland (Phragmites australis) to semi-natural [Tamarix chinensis (Tamarix)] and to cropland (Gossypium spp.). The grassland and Tamarix ecosystems were not subject to any management practice, while the cropland received fertilizer and irrigation. Overall, median N2O flux was significantly different among the ecosystems with the highest from the cropland (25.3 N2O-N µg m−2 h−1), intermediate (8.2 N2O-N µg m−2 h−1) from the Tamarix and the lowest (4.0 N2O-N µg m−2 h−1) from the grassland ecosystem. The 15N isotopic signatures in N2O emitted from the soil were also significantly affected by the LUC with more depleted from cropland (− 25.3 ‰) and less depleted from grassland (− 0.18 ‰). Our results suggested that the conversion of native saline–alkaline grassland with low N to Tamarix or cropland is likely to result in increased soil N2O emission and also contributes significantly to the depletion of the 15N in atmospheric N2O, and the contribution of anthropogenic N addition was found more significant than any other processes.
Differential impact of endogenous and exogenous attention on activity in human visual cortex
Authors: Dugué Laura , Merriam Elisha P. , Heeger David J. , Carrasco Marisa
Published: December 2020

How do endogenous (voluntary) and exogenous (involuntary) attention modulate activity in visual cortex? Using ROI-based fMRI analysis, we measured fMRI activity for valid and invalid trials (target at cued/un-cued location, respectively), pre- or post-cueing endogenous or exogenous attention, while participants performed the same orientation discrimination task. We found stronger modulation in contralateral than ipsilateral visual regions, and higher activity in valid- than invalid-trials. For endogenous attention, modulation of stimulus-evoked activity due to a pre-cue increased along the visual hierarchy, but was constant due to a post-cue. For exogenous attention, modulation of stimulus-evoked activity due to a pre-cue was constant along the visual hierarchy, but was not modulated due to a post-cue. These findings reveal that endogenous and exogenous attention distinctly modulate activity in visuo-occipital areas during orienting and reorienting; endogenous attention facilitates both the encoding and the readout of visual information whereas exogenous attention only facilitates the encoding of information.
Vegetation degradation impacts soil nutrients and enzyme activities in wet meadow on the Qinghai-Tibet Plateau
Authors: Wu Jiangqi , Wang Haiyan , Li Guang , Ma Weiwei , Wu Jianghua , Gong Yu , Xu Guorong
Published: December 2020

Vegetation degradation, due to climate change and human activities, changes the biomass, vegetation species composition, and soil nutrient input sources and thus affects soil nutrient cycling and enzyme activities. However, few studies have focused on the responses of soil nutrients and enzymes to vegetation degradation in high-altitude wet meadows. In this study, we examined the effects of vegetation degradation on soil nutrients (soil organic carbon, SOC; total nitrogen, TN; total phosphorus, TP) and enzyme activities (i.e., urease, catalase, amylase) in an alpine meadow in the eastern margin of the Qinghai-Tibet Plateau. Four different levels of degradation were defined in terms of vegetation density and composition: primary wet meadow (CK), lightly degraded (LD), moderately degraded (MD), and heavily degraded (HD). Soil samples were collected at depth intervals of 0–10, 10–20, 20–40, 40–60, 60–80, and 80–100 cm to determine soil nutrient levels and enzyme activities. The results showed that SOC, TN, catalase and amylase significantly decreased with degradation level, while TP and urease increased with degradation level (P < 0.05). Soil nutrient and enzyme activity significantly decreased with soil depth (P < 0.05), and the soil nutrient and enzyme activity exhibited obvious "surface aggregation". The activities of soil urease and catalase were strongest in spring and weakest in winter. The content of TN in spring, summer, and autumn was significantly higher than observed in winter (P < 0.05). The soil TP content increased in winter. Soil amylase activity was significantly higher in summerm than in spring, autumn, and winter (P < 0.05). TP was the main limiting factor for plant growth in the Gahai wet meadow. Values of SOC and TN were positively and significantly correlated with amylase and catalase (P < 0.05), but negatively correlated with urease (P < 0.05). These results suggest the significant role that vegetation degradation and seasonal freeze–thaw cycle play in regulating enzyme activities and nutrient availability in wet meadow soil.
Flickering candle flames and their collective behavior
Authors: Gergely Attila , Sándor Bulcsú , Paizs Csaba , Tötös Robert , Néda Zoltán
Published: December 2020

Oscillation and collective behavior of diffusion flames is a fascinating phenomena. Considering candle bundles with different sizes in variable oxygen concentration, the flickering dynamics of the flames are experimentally and theoretically investigated. Trends for the flickering frequency as a function of the candle number in the bundle and oxygen concentration is revealed for various topologies of the candles packing. The collective behavior of the flames as a function of their separation distance is studied by measuring an appropriate synchronization order parameter and through the common oscillation frequency. In agreement with previous results we find a discontinuous phase transition between an in-phase synchronized state at small separation distance and a counter-phase synchronized state at larger separation distances. A previously used dynamical model is modified in order to accommodate our experimental findings.
Increasing prosocial behavior and decreasing selfishness in the lab and everyday life
Authors: Gloster Andrew T. , Rinner Marcia T. B. , Meyer Andrea H.
Published: December 2020

The tension between selfishness and prosocial behavior is crucial to understanding many social interactions and conflicts. Currently little is known how to promote prosocial behaviors, especially in naturally occurring relationships outside the laboratory. We examined whether a psychological micro-intervention would promote prosocial behaviors in couples. Across two studies, we randomized dyads of couples to a micro-intervention (15 min), which increased prosocial behaviors by 28% and decreased selfish behaviors by 35% a week later in behavioral games in a dose–response manner. Using event sampling methodology, we further observed an increase in prosocial behaviors across one week that was most pronounced in participants who received the intervention. These results from the laboratory and everyday life are important for researchers interested in prosocial behavior and selfishness and have practical relevance for group interactions.
Chemical composition, antioxidant capacity, and thermal behavior of Satureja hortensis essential oil
Authors: Chambre Dorina Rodica , Moisa Cristian , Lupitu Andreea , Copolovici Lucian , Pop Georgeta , Copolovici Dana-Maria
Published: December 2020

Saturejahortensis is one of the representative plants from the Lamiaceae family, and its essential oil has been used in various applicative fields, from the food industry to aromatherapy. The changes that occur in heated samples at different temperatures (160, 175, 190 ºC) over different periods (0.5 and 2.5 h) in Saturejahortensis essential oil composition and chemical properties were evaluated. The results showed that the major chemical composition constituents of the investigated essential oil are γ-terpinene + α-terpinolene and carvacrol + p-cymene and the thermal behavior is dependent on the content. This composition drastically changes through the heating of the samples and causes significant changes in thermal behavior. The present study demonstrated that the concentration of carvacrol in S.hortensis essential oil is increasing after heating treatment, and the sample heated at 190 ºC for 2.5 h contained more than 91% carvacrol. This simple treatment is a rapid way to obtain carvacrol from the essential oil that has high potential as a natural preservative suitable for the food industry and alternative and complementary medicine.
Met125 is essential for maintaining the structural integrity of calmodulin’s C-terminal domain
Authors: Nelson Sarah E. D. , Weber Daniel K. , Rebbeck Robyn T. , Cornea Razvan L. , Veglia Gianluigi , Thomas David D.
Published: December 2020

We have used NMR and circular dichroism spectroscopy to investigate the structural and dynamic effects of oxidation on calmodulin (CaM), using peroxide and the Met to Gln oximimetic mutations. CaM is a Ca2+-sensitive regulatory protein that interacts with numerous targets. Due to its high methionine content, CaM is highly susceptible to oxidation by reactive oxygen species under conditions of cell stress and age-related muscle degeneration. CaM oxidation alters regulation of a host of CaM’s protein targets, emphasizing the importance of understanding the mechanism of CaM oxidation in muscle degeneration and overall physiology. It has been shown that the M125Q CaM mutant can mimic the functional effects of methionine oxidation on CaM’s regulation of the calcium release channel, ryanodine receptor (RyR). We report here that the M125Q mutation causes a localized unfolding of the C-terminal lobe of CaM, preventing the formation of a hydrophobic cluster of residues near the EF-hand Ca2+ binding sites. NMR analysis of CaM oxidation by peroxide offers further insights into the susceptibility of CaM’s Met residues to oxidation and the resulting structural effects. These results further resolve oxidation-driven structural perturbation of CaM, with implications for RyR regulation and the decay of muscle function in aging.
Maternal immune activation induces sustained changes in fetal microglia motility
Authors: Ozaki Kana , Kato Daisuke , Ikegami Ako , Hashimoto Akari , Sugio Shouta , Guo Zhongtian , Shibushita Midori , Tatematsu Tsuyako , Haruwaka Koichiro , Moorhouse Andrew J. , Yamada Hideto , Wake Hiroaki
Published: December 2020

Maternal infection or inflammation causes abnormalities in brain development associated with subsequent cognitive impairment and in an increased susceptibility to schizophrenia and autism spectrum disorders. Maternal immune activation (MIA) and increases in serum cytokine levels mediates this association via effects on the fetal brain, and microglia can respond to maternal immune status, but consensus on how microglia may respond is lacking and no-one has yet examined if microglial process motility is impaired. In this study we investigated how MIA induced at two different gestational ages affected microglial properties at different developmental stages. Immune activation in mid-pregnancy increased IL-6 expression in embryonic microglia, but failed to cause any marked changes in morphology either at E18 or postnatally. In contrast MIA, particularly when induced earlier (at E12), caused sustained alterations in the patterns of microglial process motility and behavioral deficits. Our research has identified an important microglial property that is altered by MIA and which may contribute to the underlying pathophysiological mechanisms linking maternal immune status to subsequent risks for cognitive disease.
Genes, pathways and networks responding to drought stress in oil palm roots
Authors: Wang Le , Lee May , Ye Baoqing , Yue Gen Hua
Published: December 2020

Oil palm is the most productive oilseed crop and its oil yield is seriously affected by frequent drought stress. However, little is known about the molecular responses of oil palm to drought stress. We studied the root transcriptomic responses of oil palm seedlings under 14-day drought stress. We identified 1293 differentially expressed genes (DEGs), involved in several molecular processes, including cell wall biogenesis and functions, phenylpropanoid biosynthesis and metabolisms, ion transport and homeostasis and cellular ketone metabolic process, as well as small molecule biosynthetic process. DEGs were significantly enriched into two categories: hormone regulation and metabolism, as well as ABC transporters. In addition, three protein–protein interaction networks: ion transport, reactive nitrogen species metabolic process and nitrate assimilation, were identified to be involved in drought stress responses. Finally, 96 differentially expressed transcription factors were detected to be associated with drought stress responses, which were classified into 28 families. These results provide not only novel insights into drought stress responses, but also valuable genomic resources to improve drought tolerance of oil palm by both genetic modification and selective breeding.
Consistency in mutualism relies on local, rather than wider community biodiversity
Authors: Dunkley Katie , Cable Jo , Perkins Sarah E.
Published: December 2020

Mutualistic interactions play a major role in shaping the Earth’s biodiversity, yet the consistent drivers governing these beneficial interactions are unknown. Using a long-term (8 year, including > 256 h behavioural observations) dataset of the interaction patterns of a service-resource mutualism (the cleaner-client interaction), we identified consistent and dynamic predictors of mutualistic outcomes. We showed that cleaning was consistently more frequent when the presence of third-party species and client partner abundance locally increased (creating choice options), whilst partner identity regulated client behaviours. Eight of our 12 predictors of cleaner and client behaviour played a dynamic role in predicting both the quality (duration) and quantity (frequency) of interactions, and we suggest that the environmental context acting on these predictors at a specific time point will indirectly regulate their role in cleaner-client interaction patterns: context-dependency can hence regulate mutualisms both directly and indirectly. Together our study highlights that consistency in cleaner-client mutualisms relies strongly on the local, rather than wider community—with biodiversity loss threatening all environments this presents a worrying future for the pervasiveness of mutualisms.
Transcriptome comparison between pluripotent and non-pluripotent calli derived from mature rice seeds
Authors: Shim Sangrea , Kim Hee Kyoung , Bae Soon Hyung , Lee Hoonyoung , Lee Hyo Ju , Jung Yu Jin , Seo Pil Joon
Published: December 2020

In vitro plant regeneration involves a two-step practice of callus formation and de novo organogenesis. During callus formation, cellular competence for tissue regeneration is acquired, but it is elusive what molecular processes and genetic factors are involved in establishing cellular pluripotency. To explore the mechanisms underlying pluripotency acquisition during callus formation in monocot plants, we performed a transcriptomic analysis on the pluripotent and non-pluripotent rice calli using RNA-seq. We obtained a dataset of differentially expressed genes (DEGs), which accounts for molecular processes underpinning pluripotency acquisition and maintenance. Core regulators establishing root stem cell niche were implicated in pluripotency acquisition in rice callus, as observed in Arabidopsis. In addition, KEGG analysis showed that photosynthetic process and sugar and amino acid metabolism were substantially suppressed in pluripotent calli, whereas lipid and antioxidant metabolism were overrepresented in up-regulated DEGs. We also constructed a putative coexpression network related to cellular pluripotency in rice and proposed potential candidates conferring pluripotency in rice callus. Overall, our transcriptome-based analysis can be a powerful resource for the elucidation of the molecular mechanisms establishing cellular pluripotency in rice callus.
Effects of dietary organic acids and nature identical compounds on growth, immune parameters and gut microbiota of European sea bass
Authors: Busti Serena , Rossi Barbara , Volpe Enrico , Ciulli Sara , Piva Andrea , D’Amico Federica , Soverini Matteo , Candela Marco , Gatta Pier Paolo , Bonaldo Alessio , Grilli Ester , Parma Luca
Published: December 2020

A 71-day study was conducted to explore the effect of increasing dietary levels (0, 250, 500, 1000 mg kg feed−1; D0, D250, D500 and D1000, respectively) of a blend of microencapsulated organic acids (OA, specifically citric and sorbic acid) and nature identical compounds (NIC, specifically thymol and vanillin), on growth, intestinal immune parameters and gut microbiota (GM) of European sea bass juveniles reared under normal and subsequently suboptimal environmental conditions (high temperature, 30.0 ± 0.4 °C and low oxygen, 4.6 ± 0.6 mg L−1). OA and NIC did not promote growth, feed utilisation and feed intake at the inclusion tested but induced a significantly upregulation of IL-8, IL-10 and TGFβ. GM analyzed by next-generation sequencing showed that OA and NIC were able to exert prebiotic properties stimulating the development of beneficial bacteria taxa such asLactobacillus,Leuconostoc, andBacillussp. Picrust analyses displayed a significant potential functional reconfiguration of GM promoting a decrease in inflammation-promoting and homeostatic functions at increasing OA and NIC administration. For the first time on this species the exposure to suboptimal rearing conditions was able to modify GM structure reducing LAB and increasing Proteobacteria, findings which were consistent with the inflammatory process observed at mRNA level.
Development of a novel risk score to predict mortality in patients admitted to hospital with COVID-19
Authors: Gue Ying X. , Tennyson Maria , Gao Jovia , Ren Shuhui , Kanji Rahim , Gorog Diana A.
Published: December 2020

Patients hospitalised with COVID-19 have a high mortality. Identification of patients at increased risk of adverse outcome would be important, to allow closer observation and earlier medical intervention for those at risk, and to objectively guide prognosis for friends and family of affected individuals. We conducted a single-centre retrospective cohort study in all-comers with COVID-19 admitted to a large general hospital in the United Kingdom. Clinical characteristics and features on admission, including observations, haematological and biochemical characteristics, were used to develop a score to predict 30-day mortality, using multivariable logistic regression. We identified 316 patients, of whom 46% died within 30-days. We developed a mortality score incorporating age, sex, platelet count, international normalised ratio, and observations on admission including the Glasgow Coma Scale, respiratory rate and blood pressure. The score was highly predictive of 30-day mortality with an area under the receiver operating curve of 0.7933 (95% CI 0.745–0.841). The optimal cut-point was a score ≥ 4, which had a specificity of 78.36% and a sensitivity of 67.59%. Patients with a score ≥ 4 had an odds ratio of 7.6 for 30-day mortality compared to those with a score < 4 (95% CI 4.56–12.49, p < 0.001). This simple, easy-to-use risk score calculator for patients admitted to hospital with COVID-19 is a strong predictor of 30-day mortality. Whilst requiring further external validation, it has the potential to guide prognosis for family and friends, and to identify patients at increased risk, who may require closer observation and more intensive early intervention.
Age related extracellular matrix and interstitial cell phenotype in pulmonary valves
Authors: Wu Shaohua , Kumar Vikas , Xiao Peng , Kuss Mitchell , Lim Jung Yul , Guda Chittibabu , Butcher Jonathan , Duan Bin
Published: December 2020

Heart valve disease is a common manifestation of cardiovascular disease and is a significant cause of cardiovascular morbidity and mortality worldwide. The pulmonary valve (PV) is of primary concern because of its involvement in common congenital heart defects, and the PV is usually the site for prosthetic replacement following a Ross operation. Although effects of age on valve matrix components and mechanical properties for aortic and mitral valves have been studied, very little is known about the age-related alterations that occur in the PV. In this study, we isolated PV leaflets from porcine hearts in different age groups (~ 4–6 months, denoted as young versus ~ 2 years, denoted as adult) and studied the effects of age on PV leaflet thickness, extracellular matrix components, and mechanical properties. We also conducted proteomics and RNA sequencing to investigate the global changes of PV leaflets and passage zero PV interstitial cells in their protein and gene levels. We found that the size, thickness, elastic modulus, and ultimate stress in both the radial and circumferential directions and the collagen of PV leaflets increased from young to adult age, while the ultimate strain and amount of glycosaminoglycans decreased when age increased. Young and adult PV had both similar and distinct protein and gene expression patterns that are related to their inherent physiological properties. These findings are important for us to better understand the physiological microenvironments of PV leaflet and valve cells for correctively engineering age-specific heart valve tissues.