bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing Tropical Cyclones in the Energy Exascale Earth System Model Version 1
Authors: Balaguru Karthik , Leung L. Ruby , Van Roekel Luke P. , Golaz Jean‐Christophe , Ullrich Paul A. , Caldwell Peter M. , Hagos Samson M. , Harrop Bryce E. , Mametjanov Azamat
Published: July 2020

In this study, we analyze the realism with which tropical cyclones (TCs) are simulated in the fully coupled low‐ and high‐resolution Energy Exascale Earth System Model (E3SM) version 1, with a focus on the latter. Compared to the low‐resolution (grid spacing of ∼1°), the representation of TCs improves considerably in the high‐resolution configuration (grid spacing of ∼0.25°). Significant improvements are found in the global TC frequency, TC lifetime maximum intensities, and the relative distribution of TCs among the different basins. However, at both resolutions, spurious TC activity is found in some basins, notably in the subtropical regions. Contrasting the simulated large‐scale TC environment with observations reveals that the model environment is unrealistically conducive for TC development in those regions. Further analysis indicates that these biases are likely related to those in thermodynamic potential intensity, caused by systematic SST biases, and vertical wind shear in the coupled model. TC‐ocean interaction is also examined in the high‐resolution configuration of the model. The salient features of the ocean's response to TC‐induced mixing and the ocean's impact on TC intensification are well‐reproduced. Finally, an evaluation of the influence of El Niño Southern Oscillation (ENSO) on TCs in the high‐resolution configuration of the model reveals that the ENSO‐TC relationship in the model has the right sign and is significant for the North Atlantic and Northwest Pacific, albeit weaker than in observations. In summary, the high‐resolution configuration of the E3SM model simulates TC activity reasonably and hence could be a useful tool for TC‐related research.
Latitudinal Variation in Plankton Traits and Ecosystem Function
Authors: Chakraborty Subhendu , Cadier Mathilde , Visser André W. , Bruggeman Jorn , Andersen Ken H.
Published: July 2020

Planktonic ecosystems are usually modeled in terms of autotrophic and heterotrophic compartments. However, the trophic strategy of unicellular organisms can take a range of mixotrophic strategies with both autotrophic and heterotrophic contributions. The dominant emerging strategy found in nature depends on the environment (both biotic and abiotic aspects) and the cell size and influences key ecosystem functions like trophic transfer and carbon export. Ecosystem models that faithfully represent this diversity of trophic strategies are lacking. Here we develop a trait‐based model of unicellular plankton with cell size as the master trait and three other traits that determine trophic strategies: investments in photosynthesis, nutrient uptake, and phagotrophy. This unicellular model spans the entire auto‐ mixo‐ hererotrophic strategy continuum and the entire size range of unicellular organisms. The model reproduces observed latitudinal patterns in biomass, primary productivity, vertical carbon export, and energy transfer efficiency; all increase with increasing latitude. The size range of mixotrophic cells is independent of the season at low latitudes. At high latitudes, the dominance of pure phototrophs during early spring restricts mixotrophic behavior to a narrower range of cell sizes and with the occurrence of relatively smaller mixotrophs during summer. The model's ability to adapt to different environmental conditions, combined with its simple conceptual structure and low number of parameters and state variables (10), makes it ideally suited for global simulation studies under changing environmental conditions.
Dynamic Amplification of Subtropical Extreme Precipitation in a Warming Climate
Authors: Norris Jesse , Chen Gang , Li Chao
Published: July 2020

Projected precipitation changes in a warming climate vary considerably, spatially, and between intensities. The changes can be greater or less than the ∼7% K−1 Clausius‐Clapeyron (CC) prediction, owing to dynamic effects. Using two global‐climate‐model large ensembles, we quantify the dynamically induced changes to precipitation extremes from the present (1996–2005) to late‐21st‐century (2071–2080) climates, as a function of recurrence interval, focusing on the subtropics. We separate non‐CC changes into a term proportional to the present‐day vertical‐velocity spatial pattern (i.e., an amplification or damping thereof by a constant factor) and a residual. The amplitude term varies with recurrence interval, approximately canceling (doubling) CC for moderate (large) extremes, increasing precipitation variability. Contrastingly, the residual is quasi‐uniform across recurrence intervals but spatially heterogeneous, weakening extremes over dry zones. This residual may be related to Hadley cell expansion, although this explanation is insufficient to explain many features, and other possible mechanisms are discussed.
p190A RhoGAP induces CDH1 expression and cooperates with E-cadherin to activate LATS kinases and suppress tumor cell growth
Authors: Ouyang Hanyue , Luong Phi , Frödin Morten , Hansen Steen H.
Published: July 2020

The ARHGAP35 gene encoding p190A RhoGAP (p190A) is significantly altered by both mutation and allelic deletion in human cancer, but the functional implications of such alterations are not known. Here, we demonstrate for the first time that p190A is a tumor suppressor using a xenograft mouse model with carcinoma cells harboring defined ARHGAP35 alterations. In vitro, restoration of p190A expression in carcinoma cells promotes contact inhibition of proliferation (CIP) through activation of LATS kinases and phosphorylation of the proto-oncogenic transcriptional co-activator YAP. In contrast, p190A forms harboring recurrent cancer mutations exhibit loss of function in modulating the Hippo pathway, inducing CIP, as well as attenuated suppression of tumor growth in mice. We determine that p190A promotes mesenchymal to epithelial transition (MET) and elicits expression of a cassette of epithelial adherens junction-associated genes in a cell density-dependent manner. This cassette includes CDH1 encoding E-cadherin, which amplifies p190A-mediated LATS activation and is necessary for CIP. Oppositely, we establish that p190A is obligatory for E-cadherin to activate LATS kinases and induce CIP. Collectively, this work defines a novel mechanism by which p190A and E-cadherin cooperate in modulating Hippo signaling to suppress tumor cell growth.
Early treatment-related neutropenia predicts response to palbociclib
Authors: McAndrew Nicholas P. , Dickson Mark A. , Clark Amy S. , Troxel Andrea B. , O’Hara Mark H. , Colameco Christopher , Gallager Maryann , Gramlich Kristi , Zafman Kelly , Vaughn David , Schwartz Gary K. , O’Dwyer Peter J. , DeMichele Angela
Published: July 2020

Background

Palbociclib is highly active in oestrogen-receptor positive (ER+) metastatic breast cancer, but neutropenia is dose limiting. The goal of this study was to determine whether early neutropenia is associated with disease response to single-agent palbociclib.

Methods

Blood count and disease-response data were analysed from two Phase 2 clinical trials at different institutions using single-agent palbociclib: advanced solid tumours positive for retinoblastoma protein and advanced liposarcoma. The primary endpoint was PFS. The primary exposure variable was the nadir absolute neutrophil count (ANC) during the first two cycles of treatment.

Results

One hundred and ninety-six patients (61 breast, 135 non-breast) were evaluated between the two trials. Development of any grade neutropenia was significantly associated with longer median PFS in both the breast cancer (HR 0.29, 95% CI 0.11–0.74, p = 0.010) and non-breast cancer (HR 0.57, 95% CI 0.38–0.85, p = 0.006) cohorts. Grade 3–4 neutropenia was significantly associated with prolonged PFS in the non-breast cohort (HR 0.57, 95% CI 0.38–0.85, p = 0.006) but not in the breast cohort (HR 0.87, 95% CI 0.51–1.47, p = 0.596). Multivariate analysis yielded similar results.

Conclusions

Treatment-related neutropenia in the first two cycles was significantly and independently associated with prolonged PFS, suggesting that neutropenia may be a useful pharmacodynamic marker to guide individualised palbociclib dosing.

Clinical trials registration information

Basket Trial: NCT01037790; Sarcoma Trial: NCT01209598.
PIM2 promotes hepatocellular carcinoma tumorigenesis and progression through activating NF-κB signaling pathway
Authors: Tang Xuming , Cao Tingting , Zhu Yun , Zhang Liyi , Chen Jinna , Liu Tengfei , Ming Xiaoyan , Fang Shuo , Yuan Yun-fei , Jiang Lingxi , Huang Jian-Dong , Guan Xin-Yuan
Published: July 2020

Inflammatory factors and activation of oncogenes both played critical roles in the development and progression of human hepatocellular carcinoma (HCC). However, the interplay between these two has not been well studied. In this study, we found that regulated by TNFα, Pim-2 proto-oncogene, serine/threonine kinase (PIM2) was highly expressed in HCC and correlated with poor prognosis (P = 0.007) as well as tumor recurrence (P = 0.014). Functional studies showed that PIM2 could enhance abilities of cell proliferation, cell motility, angiogenesis, chemo-resistance, and in vivo tumorigenicity and HCC metastasis. Mechanistic studies revealed that PIM2 could activate NF-κB signaling pathway through upregulating phosphorylation level of RIPK2. Interestingly, TNFα treatment could induce the expression of PIM2, and overexpression of PIM2 could in turn upregulate the expression of TNFα in HCC cells. More importantly, we found the expression level of PIM2 increased with the progression of liver cirrhosis, and PIM kinase inhibitor AZD1208 treatment could effectively attenuate HCC cells’ tumorigenic ability both in vitro and in vivo. Collectively, our study revealed the interaction between an inflammatory factor and a proto-oncogene that contributed to tumorigenesis and progression of HCC, and PIM kinase inhibition may serve as a therapeutic target in the treatment of HCC.
Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
Authors: Feng Ye , Zhong Xin , Tang Tao-Tao , Wang Cui , Wang Li-Ting , Li Zuo-Lin , Ni Hai-Feng , Wang Bin , Wu Min , Liu Dan , Liu Hong , Tang Ri-Ning , Liu Bi-Cheng , Lv Lin-Li
Published: July 2020

Exosomes are increasingly recognized as vehicles of intercellular communication. However, the role of exosome in maintaining cellular homeostasis under stress conditions remained unclear. Here we show that Rab27a expression was upregulated exclusively in tubular epithelial cells (TECs) during proteinuria nephropathy established by adriamycin (ADR) injection and 5/6 nephrectomy as well as in chronic kidney disease patients, leading to the increased secretion of exosomes carrying albumin. The active exosome production promoted tubule injury and inflammation in neighboring and the producing cells. Interferon regulatory factor 1 (IRF-1) was found as the transcription factor contributed to the upregulation of Rab27a. Albumin could be detected in exosome fraction and co-localized with exosome marker CD63 indicating the secretion of albumin into extracellular space by exosomes. Interestingly, inhibition of exosome release accelerated albumin degradation which reversed tubule injury with albumin overload, while lysosome suppression augmented exosome secretion and tubule inflammation. Our findings revealed that IRF-1/Rab27a mediated exosome secretion constituted a coordinated approach to lysosome degradation for albumin handling, which lead to the augment of albumin toxicity as a maladaptive response to maintain cell homeostasis. The findings may suggest a novel therapeutic strategy for proteinuric kidney disease by targeting exosome secretion.
BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?
Authors: Sharma Abhibhav , Kumar Sharma Saurabh , Shi Yufang , Bucci Enrico , Carafoli Ernesto , Melino Gerry , Bhattacherjee Arnab , Das Gobardhan
Published: July 2020

Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette–Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity.
Is hydroxychloroquine beneficial for COVID-19 patients?
Authors: Li Xing , Wang Ying , Agostinis Patrizia , Rabson Arnold , Melino Gerry , Carafoli Ernesto , Shi Yufang , Sun Erwei
Published: July 2020

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world1–3, the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 20204. The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir5, to control the disease and halt the pandemic.
Autophagy as a modulator of cell death machinery
Authors: Noguchi Masayuki , Hirata Noriyuki , Tanaka Tsutomu , Suizu Futoshi , Nakajima Hiroshi , Chiorini John A.
Published: July 2020

The balance between cell death and survival is a critical parameter in the regulation of cells and the maintenance of homeostasis in vivo. Three major mechanisms for cell death have been identified in mammalian cells: apoptosis (type I), autophagic cell death (type II), and necrosis (type III). These three mechanisms have been suggested to engage in cross talk with each other. Among them, autophagy was originally characterized as a cell survival mechanism for amino acid recycling during starvation. Whether autophagy functions primarily in cell survival or cell death is a critical question yet to be answered. Here, we present a comprehensive review of the cell death-related events that take place during autophagy and their underlying mechanisms in cancer and autoimmune disease development.
Publisher Correction: Hydrolase–like catalysis and structural resolution of natural products by a metal–organic framework
Authors: Mon Marta , Bruno Rosaria , Sanz-Navarro Sergio , Negro Cristina , Ferrando-Soria Jesús , Bartella Lucia , Di Donna Leonardo , Prejanò Mario , Marino Tiziana , Leyva-Pérez Antonio , Armentano Donatella , Pardo Emilio
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: In-cell identification and measurement of RNA-protein interactions
Authors: Graindorge Antoine , Pinheiro Inês , Nawrocka Anna , Mallory Allison C. , Tsvetkov Peter , Gil Noa , Carolis Carlo , Buchholz Frank , Ulitsky Igor , Heard Edith , Taipale Mikko , Shkumatava Alena
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Land-use change interacts with climate to determine elevational species redistribution
Authors: Guo Fengyi , Lenoir Jonathan , Bonebrake Timothy C.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice
Authors: Yang Lei , Ton Hoai , Zhao Ruohe , Geron Erez , Li Mengzhu , Dong Yuanlin , Zhang Yiying , Yu Buwei , Yang Guang , Xie Zhongcong
Published: July 2020

Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of sevoflurane. We found that sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.
Dextran-coated iron oxide nanoparticle-induced nanotoxicity in neuron cultures
Authors: Badman Ryan P. , Moore Shanna L. , Killian Jessica L. , Feng Tuancheng , Cleland Thomas A. , Hu Fenghua , Wang Michelle D.
Published: July 2020

Recent technological advances have introduced diverse engineered nanoparticles (ENPs) into our air, water, medicine, cosmetics, clothing, and food. However, the health and environmental effects of these increasingly common ENPs are still not well understood. In particular, potential neurological effects are one of the most poorly understood areas of nanoparticle toxicology (nanotoxicology), in that low-to-moderate neurotoxicity can be subtle and difficult to measure. Culturing primary neuron explants on planar microelectrode arrays (MEAs) has emerged as one of the most promising in vitro techniques with which to study neuro-nanotoxicology, as MEAs enable the fluorescent tracking of nanoparticles together with neuronal electrical activity recording at the submillisecond time scale, enabling the resolution of individual action potentials. Here we examine the dose-dependent neurotoxicity of dextran-coated iron oxide nanoparticles (dIONPs), a common type of functionalized ENP used in biomedical applications, on cultured primary neurons harvested from postnatal day 0–1 mouse brains. A range of dIONP concentrations (5–40 µg/ml) were added to neuron cultures, and cells were plated either onto well plates for live cell, fluorescent reactive oxidative species (ROS) and viability observations, or onto planar microelectrode arrays (MEAs) for electrophysiological measurements. Below 10 µg/ml, there were no dose-dependent cellular ROS increases or effects in MEA bursting behavior at sub-lethal dosages. However, above 20 µg/ml, cell death was obvious and widespread. Our findings demonstrate a significant dIONP toxicity in cultured neurons at concentrations previously reported to be safe for stem cells and other non-neuronal cell types.
New methodology to process shifted excitation Raman difference spectroscopy data: a case study of pollen classification
Authors: Korinth F. , Mondol A. S. , Stiebing C. , Schie I. W. , Krafft C. , Popp J.
Published: July 2020

Shifted excitation Raman difference spectroscopy (SERDS) is a background correction method for Raman spectroscopy. Here, the difference spectra were directly used as input for SERDS-based classification after an optimization procedure to correct for photobleaching of the autofluorescence. Further processing included a principal component analysis to compensate for the reduced signal to noise ratio of the difference spectra and subsequent classification by linear discriminant analysis. As a case study 6,028 Raman spectra of single pollen originating from plants of eight different genera and four different growth habits were automatically recorded at excitation wavelengths 784 and 786 nm using a high-throughput screening Raman system. Different pollen were distinguished according to their growth habit, i.e. tree versus non-tree with an accuracy of 95.9%. Furthermore, all pollen were separated according to their genus, providing also insight into similarities based on their families. Classification results were compared using spectra reconstructed from the differences and raw spectra after state-of-art baseline correction as input. Similar sensitivities, specificities, accuracies and precisions were found for all spectra with moderately background. Advantages of SERDS are expected in scenarios where Raman spectra are affected by variations due to detector etaloning, ambient light, and high background.
Author Correction: Reinterpretation of common pathogenic variants in ClinVar revealed a high proportion of downgrades
Authors: Xiang Jiale , Yang Jiyun , Chen Lisha , Chen Qiang , Yang Haiyan , Sun Chengcheng , Zhou Qing , Peng Zhiyu
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
New natural agonists of the transient receptor potential Ankyrin 1 (TRPA1) channel
Authors: Legrand Coline , Merlini Jenny Meylan , de Senarclens-Bezençon Carole , Michlig Stéphanie
Published: July 2020

The transient receptor potential (TRP) channels family are cationic channels involved in various physiological processes as pain, inflammation, metabolism, swallowing function, gut motility, thermoregulation or adipogenesis. In the oral cavity, TRP channels are involved in chemesthesis, the sensory chemical transduction of spicy ingredients. Among them, TRPA1 is activated by natural molecules producing pungent, tingling or irritating sensations during their consumption. TRPA1 can be activated by different chemicals found in plants or spices such as the electrophiles isothiocyanates, thiosulfinates or unsaturated aldehydes. TRPA1 has been as well associated to various physiological mechanisms like gut motility, inflammation or pain. Cinnamaldehyde, its well known potent agonist from cinnamon, is reported to impact metabolism and exert anti-obesity and anti-hyperglycemic effects. Recently, a structurally similar molecule to cinnamaldehyde, cuminaldehyde was shown to possess anti-obesity and anti-hyperglycemic effect as well. We hypothesized that both cinnamaldehyde and cuminaldehyde might exert this metabolic effects through TRPA1 activation and evaluated the impact of cuminaldehyde on TRPA1. The results presented here show that cuminaldehyde activates TRPA1 as well. Additionally, a new natural agonist of TRPA1, tiglic aldehyde, was identified and p-anisaldehyde confirmed.
Free l-glutamate-induced modulation in oxidative and neurochemical profile contributes to enhancement in locomotor and memory performance in male rats
Authors: Tabassum Saiqa , Ahmad Saara , Madiha Syeda , Shahzad Sidrah , Batool Zehra , Sadir Sadia , Haider Saida
Published: July 2020

Glutamate (Glu), the key excitatory neurotransmitter in the central nervous system, is considered essential for brain functioning and has a vital role in learning and memory formation. Earlier it was considered as a harmful agent but later found to be useful for many body functions. However, studies regarding the effects of free l-Glu administration on CNS function are limited. Therefore, current experiment is aimed to monitor the neurobiological effects of free l-Glu in male rats. l-Glu was orally administered to rats for 5-weeks and changes in behavioral performance were monitored. Thereafter, brain and hippocampus were collected for oxidative and neurochemical analysis. Results showed that chronic supplementation of free l-Glu enhanced locomotor performance and cognitive function of animals which may be attributed to the improved antioxidant status and cholinergic, monoaminergic and glutamatergic neurotransmission in brain and hippocampus. Current results showed that chronic supplementation of l-Glu affects the animal behaviour and brain functioning via improving the neurochemical and redox system of brain. Free l-Glu could be a useful therapeutic agent to combat neurological disturbances however this requires further targeted studies.
Sorption competition with natural organic matter as mechanism controlling silicon mobility in soil
Authors: Klotzbücher Thimo , Treptow Christian , Kaiser Klaus , Klotzbücher Anika , Mikutta Robert
Published: July 2020

Growing evidence of silicon (Si) playing an important role in plant health and the global carbon cycle triggered research on its biogeochemistry. In terrestrial soil ecosystems, sorption of silicic acid (H4SiO4) to mineral surfaces is a main control on Si mobility. We examined the competitive sorption of Si, dissolved organic matter, and phosphorus in forest floor leachates (pH 4.1–4.7) to goethite, in order to assess its effects on Si mobility at weathering fronts in acidic topsoil, a decisive zone of nutrient turnover in soil. In batch sorption experiments, we varied the extent of competition between solutes by varying the amount of added goethite (α-FeOOH) and the Si pre-loading of the goethite surfaces. Results suggest weaker competitive strength of Si than of dissolved organic matter and ortho-phosphate. Under highly competitive conditions, hardly any dissolved Si (< 2%) but much of the dissolved organic carbon (48–80%) was sorbed. Pre-loading the goethite surfaces with monomeric Si hardly decreased the sorption of organic carbon and phosphate, whereas up to about 50% of the Si was released from surfaces into solutions, indicating competitive displacement from sorption sites. We conclude sorption competition with dissolved organic matter and other strongly sorbing solutes can promote Si leaching in soil. Such effects should thus be considered in conceptual models on soil Si transport, distribution, and phytoavailability.
Self-sustained oscillations and global climate changes
Authors: Arnaut Luis G. , Ibáñez Santiago
Published: July 2020

The periodic changes of atmospheric CO2 and temperature over the last 5 Myr reveal three features that challenge current climate research, namely: (i) the mid-Pleistocene transition of dominant 41-kyr cycles to dominant 100-kyr cycles, (ii) the absence of a strong precession signal of approximately 20 kyr, and (iii) the cooling through the middle and late Holocene. These features are not directly addressable by Earth’s orbital changes described by Milankovitch. Here we show that a closed photochemical system exposed to a constant illumination source can sustain oscillations. In this simple conceptual model, the oscillations are intrinsic to the system and occur even in the absence of periodic radiative forcing. With proper adaptations to the Earth system, this oscillator explains the main features of past climate dynamics. Our model places photosynthesis and the carbon cycle as key drivers of climate change. We use this model to predict the relaxation of a 1,000 PgC pulse of CO2. The removal of 50% of this CO2 will require one century, and will lead to a warmer and wetter future. However, more pronounced glaciation cycles emerge on the millennial timescale.
Longitudinal profiling of oligomeric Aβ in human nasal discharge reflecting cognitive decline in probable Alzheimer’s disease
Authors: Yoo Seung-Jun , Son Gowoon , Bae Jisub , Kim So Yeun , Yoo Yong Kyoung , Park Dongsung , Baek Seung Yeop , Chang Keun-A , Suh Yoo-Hun , Lee Yeong-Bae , Hwang Kyo Seon , Kim YoungSoo , Moon Cheil
Published: July 2020

Despite clinical evidence indicating a close relationship between olfactory dysfunction and Alzheimer’s disease (AD), further investigations are warranted to determine the diagnostic potential of nasal surrogate biomarkers for AD. In this study, we first identified soluble amyloid-β (Aβ), the key biomarker of AD, in patient nasal discharge using proteomic analysis. Then, we profiled the significant differences in Aβ oligomers level between patient groups with mild or moderate cognitive decline (n = 39) and an age-matched normal control group (n = 21) by immunoblot analysis and comparing the levels of Aβ by a self-standard method with interdigitated microelectrode sensor systems. All subjects received the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS) for grouping. We observed higher levels of Aβ oligomers in probable AD subjects with lower MMSE, higher CDR, and higher GDS compared to the normal control group. Moreover, mild and moderate subject groups could be distinguished based on the increased composition of two oligomers, 12-mer Aβ*56 and 15-mer AβO, respectively. The longitudinal cohort study confirmed that the cognitive decline of mild AD patients with high nasal discharge Aβ*56 levels advanced to the moderate stage within three years. Our clinical evidence strongly supports the view that the presence of oligomeric Aβ proteins in nasal discharge is a potential surrogate biomarker of AD and an indicator of cognitive decline progression.
Handrail support interference in cardiac autonomic modulation adjustments in young adults during maximal exercise testing
Authors: de Oliveira Giovanna Lima , Marques Adriana Hernandez , da Fonseca Vanessa Ferrari , Pozzolo Beatriz Augusta , Panacioni Fernanda , Santos Taís Capucho , Guedes Amanda Archeleiga , Mocelin Aurenzo Gonçalves , Bertin Renata Labronici , Ulbrich Anderson Zampier
Published: July 2020

The aim of this study was to investigate whether the use of handrail support during maximal exercise treadmill testing (ETT) would interfere in cardiac autonomic modulation kinetics when compared to not using handrail support. The hypothesis of overestimation in cardiac autonomic dynamics when the ETT is performed using handrail was tested. Thirty-five undergraduates (21.08 ± 2.98 years old) of both sexes, volunteered to undertake two ETT under the Ellestad protocol, in non-consecutive days. The first test (T1) was performed with handrail support and, after 7 days, the second test was performed (T2) without the support. Autonomic function was measured by heart rate variability (HRV) during both tests and resting. Estimated value of peak oxygen uptake (VO2) was 22.4% (p < 0.0001) higher in T1 when compared to T2. Overall, parasympathetic pathway was deactivated earlier in T2 than in T1, with NNxx measures variating in T1 from 10.74 ± 14.59 (ms) and in T2 from 3.48 ± 3.79 (ms). In stage two, mean values of HF in T2 corresponded to 32% of values in T1. Stage three presented a difference of 60% (p < 0.014) in LF between means reached in T1 and T2. Lastly, the association of LF and VO2 persisted longer in T1 stages than in T2 and was verified in early stages (S2 and S3) of both ETTs. Our findings suggest that parasympathetic influences on HR were slightly prolonged during ETT when subjects hold onto the treadmill.
Histological transformation in recurrent WHO grade I meningiomas
Authors: Corniola Marco V. , Lemée Jean-Michel , Meling Torstein R.
Published: July 2020

Atypical or malignant transformation (AT/MT) has been described in WHO grade I meningiomas. Our aim was to identify predictive factors of AT/MT at recurrence. A total of N = 15 WHO grade increases were observed in N = 13 patients (0.96% of the study population, risk of transformation of 0.12% per patient-year follow-up). Patients with and without progression at recurrence were similar regarding age, gender distribution, skull-base location, bone infiltration, and Simpson grades. Recurrence-free survival was lower in patients with transformation (5 ± 4.06 years versus 7.3 ± 5.4 years; p = 0.03). Among patient age, gender, skull base location, extent of resection or post-operative RT, no predictor of AT/MT was identified, despite a follow-up of 10,524 patient-years. The annual risk of transformation of WHO grade I meningiomas was 0.12% per patient-year follow-up. Despite the important number of patients included and their extended follow-up, we did not identify any risk factor for transformation. A total of 1,352 patients with surgically managed WHO grade I meningioma from a mixed retro-and prospective database with mean follow-up of 9.2 years ± 5.7 years (0.3–20.9 years) were reviewed. Recurring tumors at the site of initial surgery were considered as recurrence.
Author Correction: The globally invasive small Indian mongoose Urva auropunctata is likely to spread with climate change
Authors: Louppe Vivien , Leroy Boris , Herrel Anthony , Veron Géraldine
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Absence of central tolerance in Aire-deficient mice synergizes with immune-checkpoint inhibition to enhance antitumor responses
Authors: Benitez Asiel A. , Khalil-Agüero Sara , Nandakumar Anjali , Gupta Namita T. , Zhang Wen , Atwal Gurinder S. , Murphy Andrew J. , Sleeman Matthew A. , Haxhinasto Sokol
Published: July 2020

The endogenous anti-tumor responses are limited in part by the absence of tumor-reactive T cells, an inevitable consequence of thymic central tolerance mechanisms ensuring prevention of autoimmunity. Here we show that tumor rejection induced by immune checkpoint blockade is significantly enhanced inAire-deficient mice, the epitome of central tolerance breakdown. The observed synergy in tumor rejection extended to different tumor models, was accompanied by increased numbers of activated T cells expressing high levels of Gzma, Gzmb, Perforin, Cxcr3, and increased intratumoural levels of Cxcl9 and Cxcl10 compared to wild-type mice. Consistent with Aire’s central role in T cell repertoire selection, single cell TCR sequencing unveiled expansion of several clones with high tumor reactivity. The data suggest that breakdown in central tolerance synergizes with immune checkpoint blockade in enhancing anti-tumor immunity and may serve as a model to unmask novel anti-tumor therapies including anti-tumor TCRs, normally purged during central tolerance.
Sex differences in SARS-CoV-2 infection rates and the potential link to prostate cancer
Authors: Chakravarty Dimple , Nair Sujit S. , Hammouda Nada , Ratnani Parita , Gharib Yasmine , Wagaskar Vinayak , Mohamed Nihal , Lundon Dara , Dovey Zachary , Kyprianou Natasha , Tewari Ashutosh K.
Published: July 2020

The recent outbreak of infections and the pandemic caused by SARS-CoV-2 represent one of the most severe threats to human health in more than a century. Emerging data from the United States and elsewhere suggest that the disease is more severe in men. Knowledge gained, and lessons learned, from studies of the biological interactions and molecular links that may explain the reasons for the greater severity of disease in men, and specifically in the age group at risk for prostate cancer, will lead to better management of COVID-19 in prostate cancer patients. Such information will be indispensable in the current and post-pandemic scenarios.
The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator
Authors: Redford Kaitlyn E. , Abbott Geoffrey W.
Published: July 2020

Many commonly consumed plants are used as folk medicines, often with unclear molecular mechanisms. Recent studies uncovered the ubiquitous and influential KCNQ family of voltage-gated potassium (Kv) channels as a therapeutic target for several medicinal plant compounds. Capers - immature flower buds of Capparis spinosa - have been consumed for food and medicinal purposes for millennia. Here, we show that caper extract hyperpolarizes cells expressing KCNQ1 or KCNQ2/3 Kv channels. Capers are the richest known natural source of quercetin, the most consumed dietary flavonoid. Quercetin potentiated KCNQ1/KCNE1, KCNQ2/3 and KCNQ4 currents but, unusually, not KCNQ5. Strikingly, quercetin augmented both activation and inactivation of KCNQ1, via a unique KCNQ activation mechanism involving sites atop the voltage sensor and in the pore. The findings uncover a novel potential molecular basis for therapeutic effects of quercetin-rich foods and a new chemical space for atypical modes of KCNQ channel modulation.
A marine photosynthetic microbial cell factory as a platform for spider silk production
Authors: Foong Choon Pin , Higuchi-Takeuchi Mieko , Malay Ali D. , Oktaviani Nur Alia , Thagun Chonprakun , Numata Keiji
Published: July 2020

Photosynthetic microorganisms such as cyanobacteria, purple bacteria and microalgae have attracted great interest as promising platforms for economical and sustainable production of bioenergy, biochemicals, and biopolymers. Here, we demonstrate heterotrophic production of spider dragline silk proteins, major ampullate spidroins (MaSp), in a marine photosynthetic purple bacterium, Rhodovulum sulfidophilum, under both photoheterotrophic and photoautotrophic growth conditions. Spider silk is a biodegradable and biocompatible material with remarkable mechanical properties. R. sulfidophilum grow by utilizing abundant and renewable nonfood bioresources such as seawater, sunlight, and gaseous CO2 and N2, thus making this photosynthetic microbial cell factory a promising green and sustainable production platform for proteins and biopolymers, including spider silks.
A lauric acid-hybridized bentonite composite phase-changing material for thermal energy storage
Authors: Liu Songyang , Han Jie , Wang Lunan , Gao Ying , Sun Hai , Li Weilong
Published: July 2020

We have developed a shape-stabilized composite phase change material (PCM) for thermal-energy storage in this work. The as-prepared LA/Na-bentonite-1 seems to be a promising shape-stabilized composite PCM candidate for thermal-energy-storage systems.
A CoOx/FeOx heterojunction on carbon nanotubes prepared by plasma-enhanced atomic layer deposition for the highly efficient electrocatalysis of oxygen evolution reactions
Authors: Yang XinXin , Sun Xiang , Gan Li-Yong , Sun Lingna , Mi Hongwei , Zhang Peixin , Ren Xiangzhong , Li Yongliang
Published: July 2020

CoOx/FeOx/CNTs show a smooth reaction path and low overpotential for OER, resulting in excellent electrocatalytic performance.
Correction: Injectable postoperative enzyme-responsive hydrogels for reversing temozolomide resistance and reducing local recurrence after glioma operation
Authors: Zhao Zongren , Shen Jiawei , Zhang Long , Wang Lansheng , Xu Haoyue , Han Yuhan , Jia Jun , Lu Yang , Yu Rutong , Liu Hongmei
Published: July 2020

Correction for ‘Injectable postoperative enzyme-responsive hydrogels for reversing temozolomide resistance and reducing local recurrence after glioma operation’ by Zongren Zhao et al., Biomater. Sci., 2020, DOI: 10.1039/d0bm00338g.
Defect-engineered UiO-66-NH2modified thin film nanocomposite membrane with enhanced nanofiltration performance
Authors: Ni Linhan , Liao Zhipeng , Chen Ke , Xie Jia , Li Qin , Qi Junwen , Sun Xiuyun , Wang Lianjun , Li Jiansheng
Published: July 2020

Defect-engineered UiO-66-NH2was introduced into a polyamide layer to form a thin film nanocomposite (TFN) membrane.
The role of anions and cations in the gas sensing mechanisms of graphene decorated with lead halide perovskite nanocrystals
Authors: Casanova-Chafer Juan , Garcia-Aboal Rocio , Atienzar Pedro , Llobet Eduard
Published: July 2020

We report the effects of both anions and cations in lead halide perovskite–graphene hybrids applied to gas sensing.
Stimuli-responsive structural changes in metal–organic frameworks
Authors: Liu Zhanning , Zhang Lu , Sun Daofeng
Published: July 2020

This feature article mainly summarizes how the structure of MOFs changes under external stimuli.
Deaminative carbonylative coupling of alkylamines with styrenes under transition-metal-free conditions
Authors: Zhao Fengqian , Li Chong-Liang , Wu Xiao-Feng
Published: July 2020

Transition-metal-free deaminative carbonylation through C–N bonds activation via Katritzky salts has been successful developed. Various α,β-unsaturated ketones were obtained in moderate to good yields with alkylamines and styrenes as the substrates.
Water-soluble amphiphilic ruthenium(ii) polypyridyl complexes as potential light-activated therapeutic agents
Authors: Estalayo-Adrián Sandra , Blasco Salvador , Bright Sandra A. , McManus Gavin J. , Orellana Guillermo , Williams D. Clive , Kelly John M. , Gunnlaugsson Thorfinnur
Published: July 2020

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.
Theoretical studies on the photochemistry of 2-nitrofluorene in the gas phase and acetonitrile solution
Authors: Li Bo , Zhang Teng-Shuo , Xue Jiadan , Xie Bin-Bin , Fang Wei-Hai , Shen Lin
Published: July 2020

The photophysics and photodegradation of 2-nitrofluorene.
Two-dimensional CaFCl: ultra-wide bandgap, strong interlayer quantum confinement, and n-type doping
Authors: Ye Xiao-Juan , Zhu Zhen-Xue , Meng Lan , Liu Chun-Sheng
Published: July 2020

Two-dimensional CaFCl: ultra-wide bandgap, strong interlayer quantum confinement, and n-type doping.
One-pot dual catalysis for the hydrogenation of heteroarenes and arenes
Authors: Chatterjee Basujit , Kalsi Deepti , Kaithal Akash , Bordet Alexis , Leitner Walter , Gunanathan Chidambaram
Published: July 2020

A catalytic system resulting from a monohydrido bridged ruthenium complex hydrogenated both heteroarenes and arenes, exhibited dual catalysis and provided access to valuable saturated heterocycles and cycloalkanes.
Realistic polyethylene terephthalate nanoplastics and the size- and surface coating-dependent toxicological impacts on zebrafish embryos
Authors: Ji Yunxia , Wang Chuyu , Wang Yunqing , Fu Longwen , Man Mingsan , Chen Lingxin
Published: July 2020

The preparation of realistic polyethylene terephthalate nanoplastics and the preliminary toxicological assessment of the as-prepared PET NPs in zebrafish embryos was carried out.
Laser-induced breakdown spectroscopy using a porous silicon substrate produced by metal-assisted etching: microanalysis of a strontium chloride aqueous solution as an example
Authors: Matsumoto Ayumu , Shimazu Yusuke , Yoshizumi Sakiko , Nakano Haruka , Yae Shinji
Published: July 2020

The LIBS signal of the dry residue from a small amount of liquid sample is significantly enhanced by using a porous silicon substrate produced by gold-nanoparticle-assisted etching.
Integrated analytical platforms for the comprehensive characterization of bioconjugated inorganic nanomaterials aiming at biological applications
Authors: Moreira-Alvarez Borja , Cid-Barrio Laura , Ferreira Hadla S. , Costa-Fernández José M. , Encinar Jorge Ruiz
Published: July 2020

The synthesis and characterization of new engineered structured inorganic nanomaterials is essential in bioanalytical research and requires for multidisciplinary analytical platforms.
Measurement of number concentrations and sizes of Au nano-particles spiked into soil by laser ablation single particle ICPMS
Authors: Tuoriniemi Jani , Holbrook Timothy R. , Cornelis Geert , Schmitt Melanie , Stärk Hans-Joachim , Wagner Stephan
Published: July 2020

A novel method to directly quantify nanoparticles (NPs) in a soil matrix by laser ablation single particle inductively coupled plasma mass spectrometry (LA-sp-ICPMS) was developed.
Haloboration: scope, mechanism and utility
Authors: Kirschner Sven , Yuan Kang , Ingleson Michael J.
Published: July 2020

Haloboration is a mostly overlooked technique, yet it is a powerful way of transforming alkynes stereoselectively into difunctionalised ambiphilic alkenes, which readily undergo a plethora of highly useful subsequent reactions.
Charge transport in MBE-grown 2H-MoTe2 bilayers with enhanced stability provided by an AlOx capping layer
Authors: Ogorzałek Zuzanna , Seredyński Bartłomiej , Kret Sławomir , Kwiatkowski Adam , Korona Krzysztof P. , Grzeszczyk Magdalena , Mierzejewski Janusz , Wasik Dariusz , Pacuski Wojciech , Sadowski Janusz , Gryglas-Borysiewicz Marta
Published: July 2020

The perfect structure of a 2H-MoTe2 bilayer in situ capped with an ultra-thin Al layer providing an excellent AlOx protection cap and long timescale stability when exposed to air and nitrogen atmospheres.
The optical nanosizer – quantitative size and shape analysis of individual nanoparticles by high-throughput widefield extinction microscopy
Authors: Payne Lukas M. , Albrecht Wiebke , Langbein Wolfgang , Borri Paola
Published: July 2020

We demonstrate rapid and quantitative nanoparticle analysis by measuring the polarisation-resolved optical extinction cross-section of hundreds of particles in wide-field microscopy, determining particle size and shapeviamodelling.
Correction and removal of expression of concern: A general and concise asymmetric synthesis of sphingosine, safingol and phytosphingosines via tethered aminohydroxylation
Authors: Kumar Pradeep , Dubey Abhishek , Puranik Vedavati G.
Published: July 2020

Correction and removal of expression of concern for ‘A general and concise asymmetric synthesis of sphingosine, safingol and phytosphingosines via tethered aminohydroxylation’ by Pradeep Kumar, et al., Org. Biomol. Chem., 2010, 8, 5074–5086, DOI: 10.1039/C0OB00117A.
Diaryliodonium as a double σ-hole donor: the dichotomy of thiocyanate halogen bonding provides divergent solid state arylation by diaryliodonium cations
Authors: Soldatova Natalia S. , Postnikov Pavel S. , Suslonov Vitalii V. , Kissler Troyana Yu. , Ivanov Daniil M. , Yusubov Mekhman S. , Galmés Bartomeu , Frontera Antonio , Kukushkin Vadim Yu.
Published: July 2020

The reactivity of [Ar1Ar2I](SCN) toward the solid-state arylation depends on the preorganization of halogen bond (XB)-bound SCN−: N-XB-bound thiocyanates, which, in contrast to N,S-XB-bound, undergoes the extremely rare N-arylation of SCN−.
New refractory MAB phases and their 2D derivatives: insight into the effects of valence electron concentration and chemical composition
Authors: Liu Yinqiao , Jiang Zhou , Jiang Xue , Zhao Jijun
Published: July 2020

Since MAB (where M is a transition metal, A is a group 13–16 element, and B is boron) phases possess several useful properties, it is meaningful to develop a database to help us figure out optimal compositions and further promote their applications.
A convenient method for synthesis of terpyridinesviaa cooperative vinylogous anomeric based oxidation
Authors: Karimi Fatemeh , Yarie Meysam , Zolfigol Mohammad Ali
Published: July 2020

Fe3O4@O2PO2(CH2)2NH3+CF3CO2−as a retrievable nanocatalyst with magnetic properties was applied for the one pot preparation of terpyridines with good yields and short reaction timesviaa cooperative vinylogous anomeric based oxidation mechanism.