bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal Controls of CO2 and CH4 Dynamics in a Temporarily Flooded Subtropical Wetland
Authors: Gomez‐Casanovas Nuria , DeLucia Nicholas J. , DeLucia Evan H. , Blanc‐Betes Elena , Boughton Elizabeth H. , Sparks Jed , Bernacchi Carl J.
Published: February 2020

Subtropical and tropical wetlands play a prominent role in the global carbon (C) cycle; yet factors that influence their C fluxes remain uncertain. We collected measurements from a temporarily flooded subtropical wetland over 3 years to investigate environmental drivers impacting CO2 and CH4 fluxes. The wetland was a sink of CO2 (−469 to −380 g C‐CO2 · m−2 · year−1) and a source of CH4 (25.1 to 32.1 g C‐CH4 · m−2 · year−1) to the atmosphere. Dry season CH4 emissions represented 41 to 49% of the annual budget, reflecting the importance of continuous CH4 flux measurements. Gross primary productivity (GPP) increased with temperature and radiation, and the influence of VPD on GPP varied with soil inundation. Higher water tables decreased Reco and increased GPP, and a higher GPP in turn lead to enhanced Reco likely through enhancements of GPP on autotrophic respiration. This suggests that the impact of the water table on Reco depends on the cancelling effects of hydrology and GPP. Emissions of CH4 increased with soil temperature, water table, and GPP until soils were inundated at which point temperature and GPP became the main drivers. Water table and temperature influenced GPP and CH4 fluxes, and increases in GPP directly enhanced CH4 emissions. In addition to impacting C fluxes directly through water table depth, hydrology also determined the hierarchy of the dominance of factors controlling C fluxes and their response. The positive climate forcing of subtropical wetlands may be dictated by plant‐mediated and climate interactions, with hydrological factors playing a major role in determining the greenhouse gas sink or source strength of subtropical wetlands.
Production of Ancient Dissolved Organic Carbon in Arctic Ocean Sediment: A Pathway of Carbon Cycling in the Extreme Environment
Authors: Fu Wenjing , Qi Yuanzhi , Liu Yanguang , Wang Xuchen , Druffel Ellen M. , Xu Xiaomei , Ren Peng , Sun Shuwen , Fan Di
Published: February 2020

We report quantitative carbon isotope evidence showing that porewater dissolved organic carbon (DOC) is produced from different sources in Arctic Ocean sediments, resulting in dramatic changes in both δ13C and Δ14C values of DOC. The very low δ13C (−42.7‰) and Δ14C (−947‰) values measured for porewater DOC indicate that bacteria consume methane hydrate‐derived OC and convert a significant fraction of this δ13C depleted and old OC (44–97%) into DOC in the sediments of the Arctic Ocean. We suggest that the production of extremely old, methane‐derived porewater DOC (5,430–23,600 years) in Arctic Ocean sediment is an important pathway for carbon cycling that provides not only a necessary energy source for microbial communities in this extreme environment but also an ancient DOC source that could flux and contribute to the old and biologically recalcitrant DOC found in the deep ocean.
Transcriptome analysis of ankylosed primary molars with infraocclusion
Authors: Tong Annie , Chow Yuh-Lit , Xu Katie , Hardiman Rita , Schneider Paul , Tan Seong-Seng
Published: February 2020

Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded (n = 7) and non-infraoccluded (n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432 (2.3%) genes were differentially expressed between the two groups (false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez; tissues that are central to the ankylotic process. We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.
Both IDO1 and TDO contribute to the malignancy of gliomas via the Kyn–AhR–AQP4 signaling pathway
Authors: Du Lisha , Xing Zikang , Tao Bangbao , Li Tianqi , Yang Dan , Li Weirui , Zheng Yuanting , Kuang Chunxiang , Yang Qing
Published: February 2020

Indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO) initiate the first step of the kynurenine pathway (KP), leading to the transformation of l-tryptophan (Trp) into l-kynurenine (Kyn) and other downstream metabolites. Kyn is known as an endogenous ligand of the aryl hydrocarbon receptor (AhR). Activation of AhR through TDO-derived Kyn is a novel mechanism to support tumor growth in gliomas. However, the role of IDO1 and IDO2 in this mechanism is still unknown. Herein, by using clinical samples, we found that the expression and activity of IDO1 and/or TDO (IDO1/TDO) rather than IDO2 were positively correlated with the pathologic grades of gliomas. The expression of IDO1/TDO rather than IDO2 was positively correlated with the Ki67 index and overall survival. The expression of IDO1/TDO was positively correlated with the expression of aquaporin 4 (AQP4), implying the potential involvement of IDO1/TDO in glioma cell motility. Mechanistically, we found that IDO1/TDO accounted for the release of Kyn, which activated AhR to promote cell motility via the Kyn–AhR–AQP4 signaling pathway in U87MG glioma cells. RY103, an IDO1/TDO dual inhibitor, could block the IDO1/TDO–Kyn–AhR–AQP4 signaling pathway and exert anti-glioma effects in GL261 orthotopic glioma mice. Together, our results showed that the IDO1/TDO–Kyn–AhR–AQP4 signaling pathway is a new mechanism underlying the malignancy of gliomas, and suggest that both IDO1 and TDO might be valuable therapeutic targets for gliomas.
Laminar flow inhibits the Hippo/YAP pathway via autophagy and SIRT1-mediated deacetylation against atherosclerosis
Authors: Yuan Ping , Hu Qiongying , He Xuemei , Long Yang , Song Xueqin , Wu Fei , He Yanzheng , Zhou Xiangyu
Published: February 2020

Atherosclerosis is a multifactorial disease of the vasculature, and shear stress is a crucial regulator of its process. Disturbed flow promotes atherosclerotic effects, while laminar flow has a protective action on the endothelium. Hippo/YAP is a major cascade that senses various mechanical cues and mediates the expression of pro-inflammatory genes. However, the mechanism modulating the transcription factor YAP in response to different patterns of blood flow remains unclear. In this study, we provide evidence that shear stress modulates YAP activity via autophagy in endothelial cells. Laminar flow promoted the expression of the autophagic markers BECLIN 1 and LC3II/LC3I. Autophagy blockade using a chemical inhibitor repressed YAP degradation under laminar flow. Conversely, the induction of autophagy under disturbed flow partially antagonized the nuclear import and transcriptional activation of YAP. In parallel, laminar flow led to the increased expression of SIRT1 protein, a NAD+-dependent deacetylase. Further investigation showed that SIRT1-mediated YAP deacetylation. The forced expression of SIRT1 under disturbed flow effectively attenuated YAP activation and nuclear accumulation, thereby downregulating the expression of pro-inflammatory genes. In atheroprone vessels of mice receiving rapamycin to induce autophagy, the enhanced expression of SIRT1 was observed together with YAP repression. Altogether, these results show that endothelial autophagy and SIRT1 expression induced by laminar flow contribute to the inhibition of Hippo/YAP signaling and interrupt atherosclerotic plaque formation.
Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3β/FBW7-mediated Mcl-1 destabilization
Authors: Gao Feng , Yu Xinfang , Li Ming , Zhou Li , Liu Wenbin , Li Wei , Liu Haidan
Published: February 2020

Activating mutations of epidermal growth factor receptor (EGFR) play crucial roles in the oncogenesis of human non-small cell lung cancer (NSCLC). By screening 79 commercially available natural products, we found that the natural compound deguelin exhibited a profound anti-tumor effect on NSCLC via directly down-regulating of EGFR-signaling pathway. Deguelin potently inhibited in vitro EGFR kinase activity of wild type (WT), exon 19 deletion, and L858R/T790M-mutated EGFR. The in silico docking study indicated that deguelin was docked into the ATP-binding pocket of EGFRs. By suppression of EGFR signaling, deguelin inhibited anchorage-dependent, and independent growth of NSCLC cell lines, and significantly delayed tumorigenesis in vivo. Further study showed that deguelin inhibited EGFR and downstream kinase Akt, which resulted in the activation of GSK3β and eventually enhanced Mcl-1 phosphorylation at S159. Moreover, deguelin promoted the interaction between Mcl-1 and E3 ligase SCFFBW7, which enhanced FBW7-mediated Mcl-1 ubiquitination and degradation. Additionally, phosphorylation of Mcl-1 by GSK3β is a prerequisite for FBW7-mediated Mcl-1 destruction. Depletion or pharmacological inactivation of GSK3β compromised deguelin-induced Mcl-1 ubiquitination and reduction. Taken together, our data indicate that enhancement of ubiquitination-dependent Mcl-1 turnover might be a promising approach for cancer treatment.
Immuno-genomic landscape of osteosarcoma
Authors: Wu Chia-Chin , Beird Hannah C. , Andrew Livingston J. , Advani Shailesh , Mitra Akash , Cao Shaolong , Reuben Alexandre , Ingram Davis , Wang Wei-Lien , Ju Zhenlin , Hong Leung Cheuk , Lin Heather , Zheng Youyun , Roszik Jason , Wang Wenyi , Patel Shreyaskumar , Benjamin Robert S. , Somaiah Neeta , Conley Anthony P. , Mills Gordon B. , Hwu Patrick , Gorlick Richard , Lazar Alexander , Daw Najat C. , Lewis Valerae , Futreal P. Andrew
Published: February 2020

Limited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatric and adult patients with primary, relapsed, and metastatic OS. Median immune infiltrate level was lower than in other tumor types where ICI are effective, with concomitant low T-cell receptor clonalities. Neoantigen expression in OS was lacking and significantly associated with high levels of nonsense-mediated decay (NMD). Samples with low immune infiltrate had higher number of deleted genes while those with high immune infiltrate expressed higher levels of adaptive resistance pathways.PARP2expression levels were significantly negatively associated with the immune infiltrate. Together, these data reveal multiple immunosuppressive features of OS and suggest immunotherapeutic opportunities in OS patients.
Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior
Authors: Bicks Lucy K. , Yamamuro Kazuhiko , Flanigan Meghan E. , Kim Julia Minjung , Kato Daisuke , Lucas Elizabeth K. , Koike Hiroyuki , Peng Michelle S. , Brady Daniel M. , Chandrasekaran Sandhya , Norman Kevin J. , Smith Milo R. , Clem Roger L. , Russo Scott J. , Akbarian Schahram , Morishita Hirofumi
Published: February 2020

Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. We identify a specific activation pattern of parvalbumin-positive interneurons (PVIs) in dorsal-medial PFC (dmPFC) prior to an active bout, or a bout initiated by the focal mouse, but not during a passive bout when mice are explored by a stimulus mouse. Optogenetic and chemogenetic manipulation reveals that brief dmPFC-PVI activation triggers an active social approach to promote sociability. Juvenile social isolation decouples dmPFC-PVI activation from subsequent active social approach by freezing the functional maturation process of dmPFC-PVIs during the juvenile-to-adult transition. Chemogenetic activation of dmPFC-PVI activity in the adult animal mitigates juvenile isolation-induced social deficits. Therefore, social experience-dependent maturation of dmPFC-PVI is linked to long-term impacts on social behavior.
Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones
Authors: Zhang Yingqian , Zang Chuanlong , An Guoce , Shang Mengdi , Cui Zenghui , Chen Gong , Xi Zhen , Zhou Chuanzheng
Published: February 2020

Many reagents have been developed for cysteine-specific protein modification. However, few of them allow for multi-functionalization of a single Cys residue and disulfide bridging bioconjugation. Herein, we report 3-bromo-5-methylene pyrrolones (3Br-5MPs) as a simple, robust, and versatile class of reagents for cysteine-specific protein modification. These compounds can be facilely synthesized via a one-pot mild reaction and they show comparable tagging efficiency but higher cysteine specificity than the maleimide counterparts. The addition of cysteine to 3Br-5MPs generates conjugates that are amenable to secondary addition by another thiol or cysteine, making 3Br-5MPs valuable for multi-functionalization of a single cysteine and disulfide bridging bioconjugation. The labeling reaction and subsequent treatments are mild enough to produce stable and active protein conjugates for biological applications.
Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers
Authors: Li Yongsheng , Jiang Tiantongfei , Zhou Weiwei , Li Junyi , Li Xinhui , Wang Qi , Jin Xiaoyan , Yin Jiaqi , Chen Liuxin , Zhang Yunpeng , Xu Juan , Li Xia
Published: February 2020

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and they play fundamental roles in immune regulation. Here we introduce an integrated algorithm, ImmLnc, for identifying lncRNA regulators of immune-related pathways. We comprehensively chart the landscape of lncRNA regulation in the immunome across 33 cancer types and show that cancers with similar tissue origin are likely to share lncRNA immune regulators. Moreover, the immune-related lncRNAs are likely to show expression perturbation in cancer and are significantly correlated with immune cell infiltration. ImmLnc can help prioritize cancer-related lncRNAs and further identify three molecular subtypes (proliferative, intermediate, and immunological) of non-small cell lung cancer. These subtypes are characterized by differences in mutation burden, immune cell infiltration, expression of immunomodulatory genes, response to chemotherapy, and prognosis. In summary, the ImmLnc pipeline and the resulting data serve as a valuable resource for understanding lncRNA function and to advance identification of immunotherapy targets.
Purging of highly deleterious mutations through severe bottlenecks in Alpine ibex
Authors: Grossen Christine , Guillaume Frédéric , Keller Lukas F. , Croll Daniel
Published: February 2020

Human activity has caused dramatic population declines in many wild species. The resulting bottlenecks have a profound impact on the genetic makeup of a species with unknown consequences for health. A key genetic factor for species survival is the evolution of deleterious mutation load, but how bottleneck strength and mutation load interact lacks empirical evidence. We analyze 60 complete genomes of six ibex species and the domestic goat. We show that historic bottlenecks rather than the current conservation status predict levels of genome-wide variation. By analyzing the exceptionally well-characterized population bottlenecks of the once nearly extinct Alpine ibex, we find genomic evidence of concurrent purging of highly deleterious mutations but accumulation of mildly deleterious mutations. This suggests that recolonization bottlenecks induced both relaxed selection and purging, thus reshaping the landscape of deleterious mutation load. Our findings highlight that even populations of ~1000 individuals can accumulate mildly deleterious mutations. Conservation efforts should focus on preventing population declines below such levels to ensure long-term survival of species.
Publisher Correction: Unveiling the Re effect in Ni-based single crystal superalloys
Authors: Wu Xiaoxiang , Makineni Surendra Kumar , Liebscher Christian H. , Dehm Gerhard , Mianroodi Jaber Rezaei , Shanthraj Pratheek , Svendsen Bob , Bürger David , Eggeler Gunther , Raabe Dierk , Gault Baptiste
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment
Authors: Arkhipova Valentina , Guskov Albert , Slotboom Dirk J.
Published: February 2020

Glutamate transporters are cation-coupled secondary active membrane transporters that clear the neurotransmitter L-glutamate from the synaptic cleft. These transporters are homotrimers, with each protomer functioning independently by an elevator-type mechanism, in which a mobile transport domain alternates between inward- and outward-oriented states. Using single-particle cryo-EM we have determined five structures of the glutamate transporter homologue GltTk, a Na+- L-aspartate symporter, embedded in lipid nanodiscs. Dependent on the substrate concentrations used, the protomers of the trimer adopt a variety of asymmetrical conformations, consistent with the independent movement. Six of the 15 resolved protomers are in a hitherto elusive state of the transport cycle in which the inward-facing transporters are loaded with Na+ ions. These structures explain how substrate-leakage is prevented – a strict requirement for coupled transport. The belt protein of the lipid nanodiscs bends around the inward oriented protomers, suggesting that membrane deformations occur during transport.
Author Correction: Probing the physical limits of reliable DNA data retrieval
Authors: Organick Lee , Chen Yuan-Jyue , Dumas Ang Siena , Lopez Randolph , Liu Xiaomeng , Strauss Karin , Ceze Luis
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Enhanced β-adrenergic signalling underlies an age-dependent beneficial metabolic effect of PI3K p110α inactivation in adipose tissue
Authors: Araiz Caroline , Yan Anqi , Bettedi Lucia , Samuelson Isabella , Virtue Sam , McGavigan Anne K. , Dani Christian , Vidal-Puig Antonio , Foukas Lazaros C.
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Daytime symptoms of chronic obstructive pulmonary disease: a systematic review
Authors: Tsiligianni Ioanna , Kocks Janwillem W. H.
Published: February 2020

There is no single source of compiled data on symptoms experienced by patients with chronic obstructive pulmonary disease (COPD) when awake and active throughout the day. The aim of this systematic review was to evaluate the prevalence, variability, and burden (i.e., bothersomeness and/or intensity), and the impact of daytime COPD symptoms on other outcomes. The review also evaluated the impact of interventions and the measures/tools used to assess daytime COPD symptoms in patients. A systematic literature search was conducted using the primary search terms “COPD”, “symptoms”, and “daytime” in EMBASE®, MEDLINE®, MEDLINE® In-Process, and CENTRAL in 2016, followed by an additional search in 2018 to capture any new literature that was published since the last search. Fifty-six articles were included in the review. The accumulated evidence indicated that the symptomatic burden of COPD appears greatest in the morning, particularly upon waking, and that these morning symptoms have a substantial impact on patients’ ability to function normally through the day; they also worsen quality of life. A wide variety of tools were used to evaluate symptoms across the studies. The literature also confirmed the importance of pharmacotherapy in the management of daytime COPD symptoms, and in helping normalize daily functioning. More research is needed to better understand how COPD symptoms impact daily functioning and to evaluate COPD symptoms at well-defined periods throughout the day, using validated and uniform measures/tools. This will help clinicians to better define patients’ needs and take appropriate action.
Hyphal network whole field imaging allows for accurate estimation of anastomosis rates and branching dynamics of the filamentous fungus Podospora anserina
Authors: Dikec J. , Olivier A. , Bobée C. , D’Angelo Y. , Catellier R. , David P. , Filaine F. , Herbert S. , Lalanne Ch. , Lalucque H. , Monasse L. , Rieu M. , Ruprich-Robert G. , Véber A. , Chapeland-Leclerc F. , Herbert E.
Published: February 2020

The success of filamentous fungi in colonizing most natural environments can be largely attributed to their ability to form an expanding interconnected network, the mycelium, or thallus, constituted by a collection of hyphal apexes in motion producing hyphae and subject to branching and fusion. In this work, we characterize the hyphal network expansion and the structure of the fungus Podospora anserina under controlled culture conditions. To this end, temporal series of pictures of the network dynamics are produced, starting from germinating ascospores and ending when the network reaches a few centimeters width, with a typical image resolution of several micrometers. The completely automated image reconstruction steps allow an easy post-processing and a quantitative analysis of the dynamics. The main features of the evolution of the hyphal network, such as the total length L of the mycelium, the number of “nodes” (or crossing points) N and the number of apexes A, can then be precisely quantified. Beyond these main features, the determination of the distribution of the intra-thallus surfaces (Si) and the statistical analysis of some local measures of N, A and L give new insights on the dynamics of expanding fungal networks. Based on these results, we now aim at developing robust and versatile discrete/continuous mathematical models to further understand the key mechanisms driving the development of the fungus thallus.
Sustainability of spatially distributed bacteria-phage systems
Authors: Eriksen Rasmus Skytte , Mitarai Namiko , Sneppen Kim
Published: February 2020

Virulent phages can expose their bacterial hosts to devastating epidemics, in principle leading to complete elimination of their hosts. Although experiments indeed confirm a large reduction of susceptible bacteria, there are no reports of complete extinctions. We here address this phenomenon from the perspective of spatial organization of bacteria and how this can influence the final survival of them. By modelling the transient dynamics of bacteria and phages when they are introduced into an environment with finite resources, we quantify how time delayed lysis, the spatial separation of initial bacterial positions, and the self-protection of bacteria growing in spherical colonies favour bacterial survival. Our results suggest that spatial structures on the millimetre and submillimetre scale play an important role in maintaining microbial diversity.
Equilibrium Thermodynamic Properties of Aqueous Solutions of Ionic Liquid 1-Ethyl-3-Methylimidazolium Methanesulfonate [EMIM][MeSO3]
Authors: Zheng Chaolun , Zhou Jian , Pei Yong , Yang Bao
Published: February 2020

The ionic liquid 1-ethyl-3-methylimidazolium methanesulfonate ([EMIM][MeSO3]) has been considered as a promising alternative desiccant to triethylene glycol and lithium bromide commonly used in the industry. In this paper, the water activity coefficient of this binary system was measured from 303 K to 363 K with water concentration from 18% to 92%. The interaction energies between the ionic liquid molecules ($${g}_{22}$$g22) and between the ionic liquid and water molecules ($${g}_{12}$$g12) for the [EMIM][MeSO3]/water binary system were determined from the water activity coefficient data using the Non-Random Two-Liquid (NRTL) model. The magnitude of the interaction energy between the [EMIM][MeSO3] and water molecules ($${g}_{12}$$g12) was found to be in the range of 45~49 kJ/mol, which was about 20% larger than that between the water molecules ($${g}_{11}$$g11) in the [EMIM][MeSO3]/water system. The large ($${g}_{12}$$g12) can explain many observed macroscopic thermodynamic properties such as strong hygroscopicity in the ionic liquid [EMIM][MeSO3]. These interaction energies were used to determine the heat of desorption of the [EMIM][MeSO3]/water system, and the obtained heat of desorption was in good agreement with that calculated from the conventional Clausius-Clapeyron Equation.
Very high sensitivity of African rice to artificial ultraviolet-B radiation caused by genotype and quantity of cyclobutane pyrimidine dimer photolyase
Authors: Mmbando Gideon Sadikiel , Teranishi Mika , Hidema Jun
Published: February 2020

Ultraviolet-B (UVB) radiation damages plants and decreases their growth and productivity. We previously demonstrated that UVB sensitivity varies widely among Asian rice (Oryza sativaL.) cultivars and that the activity of cyclobutane pyrimidine dimer (CPD) photolyase, which repairs UVB-induced CPDs, determines UVB sensitivity. Unlike Asian rice, African rice (Oryza glaberrimaSteud. andOryza barthiiA. Chev.) has mechanisms to adapt to African climates and to protect itself against biotic and abiotic stresses. However, information about the UVB sensitivity of African rice species is largely absent. We showed that most of the African rice cultivars examined in this study were UVB-hypersensitive or even UVB-super-hypersensitive in comparison with the UVB sensitivity of AsianO. sativacultivars. The difference in UVB resistance correlated with the total CPD photolyase activity, which was determined by its activity and its cellular content. The UVB-super-hypersensitive cultivars had low enzyme activity caused by newly identified polymorphisms and low cellular CPD photolyase contents. The new polymorphisms were only found in cultivars from West Africa, particularly in those from countries believed to be centres ofO. glaberrimadomestication. This study provides new tools for improving both Asian and African rice productivity.
Self-organizing pattern of subpleural alveolar ducts
Authors: Mitzner Wayne , Loube Jeffrey , Venezia Jarrett , Scott Alan
Published: February 2020

In this study we have utilized an optical clearing method to allow visualization of a heretofore undescribed subpleural acinar structural organization in the mammalian lung. The clearing method enables visualization of the lung structure deep below the visceral pleura in intact inflated lungs. In addition to confirming previous observations that the immediate subpleural alveoli are uniform in appearance, we document for the first time that the subpleural lung parenchyma is much more uniformly organized than the internal parenchyma. Specifically, we report that below the surface layer of alveoli, there is a striking parallel arrangement of alveolar ducts that all run perpendicular to the visceral pleural surface. A three dimensional visualization of alveolar ducts allowed for a calculation of the average inner to outer duct diameter ratio of 0.53 in these subpleural ducts. This unique, self-organizing parallel duct structure likely impacts both elastic recoil and the transmission of tethering forces in healthy and diseased lungs.
A Munc18-1 mutant mimicking phosphorylation by Down Syndrome-related kinase Dyrk1a supports normal synaptic transmission and promotes recovery after intense activity
Authors: Classen Jessica , Saarloos Ingrid , Meijer Marieke , Sullivan Patrick F. , Verhage Matthijs
Published: February 2020

Phosphorylation of Munc18-1 (Stxbp1), a presynaptic organizer of synaptic vesicle fusion, is a powerful mechanism to regulate synaptic strength. Munc18-1 is a proposed substrate for the Down Syndrome-related kinase dual-specificity tyrosine phosphorylation-regulate kinase 1a (Dyrk1a) and mutations in both genes cause intellectual disability. However, the functional consequences of Dyrk1a-dependent phosphorylation of Munc18-1 for synapse function are unknown. Here, we show that the proposed Munc18-1 phosphorylation site, T479, is among the highly constrained phosphorylation sites in the coding regions of the gene and is also located within a larger constrained coding region. We confirm that Dyrk1a phosphorylates Munc18-1 at T479. Patch-clamp physiology in conditional null mutant hippocampal neurons expressing Cre and either wildtype, or mutants mimicking or preventing phosphorylation, revealed that synaptic transmission is similar among the three groups: frequency/amplitude of mEPSCs, evoked EPSCs, paired pulse plasticity, rundown kinetics upon intense activity and the readily releasable pool. However, synapses expressing the phosphomimic mutant responded to intense activity with more pronounced facilitation. These data indicate that Dyrk1a-dependent Munc18-1 phosphorylation has a minor impact on synaptic transmission, only after intense activity, and that the role of genetic variation in both genes in intellectual disability may be through different mechanisms.
Author Correction: Demonstration of facilitation between microalgae to face environmental stress
Authors: Krichen Emna , Rapaport Alain , Le Floc’h Emilie , Fouilland Eric
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Anal human papillomavirus and its associations with abnormal anal cytology among men who have sex with men
Authors: Wu Ping-Feng , Hang Jen-Fan , Strong Carol , Chen Su-Jung , Lin Li-Ya , Chen Shu-Sheng , Lai Chiung-Ru , Ku Stephane Wen-Wei , Lee Mei-Hsuan
Published: February 2020

Human papillomavirus (HPV) infection contributes to most anal cancers and premalignant intraepithelial lesions. This study investigated anal HPV infections and cytological abnormalities among men who have sex with men (MSM). Sociodemographic characteristics and sexual behaviors were collected by using a structured questionnaire. Anal cytological results were examined, and HPV genotyping was performed by the Linear Array HPV Genotyping test. Logistic regression was used to estimate risk factors and their associations with high-risk HPV infection and cytological abnormalities. Among 163 MSM, 101 were seropositive for human immunodeficiency virus (HIV) and 62 were seronegative for HIV. The overall prevalence of HPV was 66.2%. A total of 61.9% and 48.2% of participants had never acquired any of either the quadrivalent or nonavalent vaccine HPV types, respectively. Cytological findings showed 15.3% atypical squamous cells of undetermined significance, 16.6% low-grade squamous intraepithelial lesion, 4.9% atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion and 17% high-grade squamous intraepithelial lesion. The number of high-risk HPV types was the predominant risk factor for abnormal anal cytology (OR 2.02, 95% CI 1.27–3.24). Infection with high-risk HPV was a significant predictor for cytological abnormality. MSM should be encouraged to obtain the HPV vaccine.
Characterization of variations within the rumen metaproteome of Holstein dairy cattle relative to morning feed offering
Authors: Honan Mallory C. , Greenwood Sabrina L.
Published: February 2020

Few studies have utilized proteomic techniques to progress our knowledge of protein-mediated pathways within the rumen microbial community, and no previous research has used these techniques to investigate the patterns or variations of these proteins within this community. It was hypothesized that there would be fluctuations of rumen microbial protein abundances due to feed intake-mediated nutrient availability and that these could be identified using non gel-based proteomic techniques. This study investigated the fluctuations of bovine rumen metaproteome utilizing three mid to late-lactation Holsteins. Rumen fluid was collected at three timepoints on three days relative to their first morning feed offering (0 h, 4 h, and 6 h). Samples were pooled within timepoint within cow across day, analyzed using LC-MS/MS techniques, and analyzed for variations across hour of sampling using PROC MIXED of SAS with orthogonal contrasts to determine linear and quadratic effects. A total of 658 proteins were characterized across 19 microbial species, with 68 proteins identified from a variety of 15 species affected by time of collection. Translation-related proteins such as 50S and 30S ribosomal protein subunit variants and elongation factors were positively correlated with hour of sampling. Results suggest that as nutrients become more readily available, microbes shift from conversion-focused biosynthetic routes to more encompassing DNA-driven pathways.
Hepcidin-mediated Iron Regulation in P19 Cells is Detectable by Magnetic Resonance Imaging
Authors: Alizadeh Kobra , Sun Qin , McGuire Tabitha , Thompson Terry , Prato Frank S. , Koropatnick Jim , Gelman Neil , Goldhawk Donna E.
Published: February 2020

Magnetic resonance imaging can be used to track cellular activities in the body using iron-based contrast agents. However, multiple intrinsic cellular iron handling mechanisms may also influence the detection of magnetic resonance (MR) contrast: a need to differentiate among those mechanisms exists. In hepcidin-mediated inflammation, for example, downregulation of iron export in monocytes and macrophages involves post-translational degradation of ferroportin. We examined the influence of hepcidin endocrine activity on iron regulation and MR transverse relaxation rates in multi-potent P19 cells, which display high iron import and export activities, similar to alternatively-activated macrophages. Iron import and export were examined in cultured P19 cells in the presence and absence of iron-supplemented medium, respectively. Western blots indicated the levels of transferrin receptor, ferroportin and ubiquitin in the presence and absence of extracellular hepcidin. Total cellular iron was measured by inductively-coupled plasma mass spectrometry and correlated to transverse relaxation rates at 3 Tesla using a gelatin phantom. Under varying conditions of iron supplementation, the level of ferroportin in P19 cells responds to hepcidin regulation, consistent with degradation through a ubiquitin-mediated pathway. This response of P19 cells to hepcidin is similar to that of classically-activated macrophages. The correlation between total cellular iron content and MR transverse relaxation rates was different in hepcidin-treated and untreated P19 cells: slope, Pearson correlation coefficient and relaxation rate were all affected. These findings may provide a tool to non-invasively distinguish changes in endogenous iron contrast arising from hepcidin-ferroportin interactions, with potential utility in monitoring of different macrophage phenotypes involved in pro- and anti-inflammatory signaling. In addition, this work demonstrates that transverse relaxivity is not only influenced by the amount of cellular iron but also by its metabolism.
Antibiotic resistance in bacterial isolates from freshwater samples in Fildes Peninsula, King George Island, Antarctica
Authors: Jara Daniela , Bello-Toledo Helia , Domínguez Mariana , Cigarroa Camila , Fernández Paulina , Vergara Luis , Quezada-Aguiluz Mario , Opazo-Capurro Andrés , Lima Celia A. , González-Rocha Gerardo
Published: February 2020

Anthropic activity in Antarctica has been increasing considerably in recent years, which could have an important impact on the local microbiota affecting multiple features, including the bacterial resistome. As such, our study focused on determining the antibiotic-resistance patterns and antibiotic-resistance genes of bacteria recovered from freshwater samples collected in areas of Antarctica under different degrees of human influence. Aerobic heterotrophic bacteria were subjected to antibiotic susceptibility testing and PCR. The isolates collected from regions of high human intervention were resistant to several antibiotic groups, and were mainly associated with the presence of genes encoding aminoglycosides-modifying enzymes (AMEs) and extended-spectrum β-lactamases (ESBLs). Moreover, these isolates were resistant to synthetic and semi-synthetic drugs, in contrast with those recovered from zones with low human intervention, which resulted highly susceptible to antibiotics. On the other hand, we observed that zone A, under human influence, presented a higher richness and diversity of antibiotic-resistance genes (ARGs) in comparison with zones B and C, which have low human activity. Our results suggest that human activity has an impact on the local microbiota, in which strains recovered from zones under anthropic influence were considerably more resistant than those collected from remote regions.
Persistent features of intermittent transcription
Authors: Wilkinson Michael , Darmanis Spyros , Pisco Angela Oliveira , Huber Greg
Published: February 2020

Single-cell RNA sequencing is a powerful tool for exploring gene expression heterogeneity, but the results may be obscured by technical noise inherent in the experimental procedure. Here we introduce a novel parametrisation of sc-RNA data, giving estimates of the probability of activation of a gene and its peak transcription rate, which are agnostic about the mechanism underlying the fluctuations in the counts. Applying this approach to single cell mRNA counts across different tissues of adult mice, we find that peak transcription levels are approximately constant across different tissue types, in contrast to the gene expression probabilities which are, for many genes, markedly different. Many genes are only observed in a small fraction of cells. An investigation of correlation between genes activities shows that this is primarily due to temporal intermittency of transcription, rather than some genes being expressed in specialised cell types. Both the probability of activation and the peak transcription rate have a very wide ranges of values, with a probability density function well approximated by a power law. Taken together, our results indicate that the peak rate of transcription is a persistent property of a gene, and that differences in gene expression are modulated by temporal intermittency of the transcription.
An exonic insertion in the NAGLU gene causing Mucopolysaccharidosis IIIB in Schipperke dogs
Authors: Raj Karthik , Ellinwood N. Matthew , Giger Urs
Published: February 2020

Mucopolysaccharidosis (MPS) IIIB (Sanfilippo syndrome B; OMIM 252920), is a lysosomal storage disease with progressive neurological signs caused by deficient activity of alpha-N-acetylglucosaminidase (NAGLU, EC 3.2.1.50). Herein we report the causative variant in the NAGLU gene in Schipperke dogs and a genotyping survey in the breed. All six exons and adjacent regions of the NAGLU gene were sequenced from six healthy appearing and three affected Schipperkes. DNA fragment length and TaqMan assays were used to genotype privately owned Schipperkes. A single variant was found in exon 6 of MPS IIIB affected Schipperkes: an insertion consisting of a 40–70 bp poly-A and an 11 bp duplication of the exonic region preceding the poly-A (XM_548088.6:c.2110_2111ins[A(40_70);2100_2110]) is predicted to insert a stretch of 13 or more lysines followed by either an in-frame insertion of a repeat of the four amino acids preceding the lysines, or a frameshift. The clinically affected Schipperkes were homozygous for this insertion, and the sequenced healthy dogs were either heterozygous or homozygous for the wild-type allele. From 2003–2019, 3219 Schipperkes were genotyped. Of these, 1.5% were homozygous for this insertion and found to be clinically affected, and 23.6% were heterozygous for the insertion and were clinically healthy, the remaining 74.9% were homozygous for the wild-type and were also clinically healthy. The number of dogs homozygous and heterozygous for the insertion declined rapidly after the initial years of genotyping, documenting the benefit of a DNA screening program in a breed with a small gene pool. In conclusion, a causative NAGLU variant in Schipperke dogs with MPS IIIB was identified and was found at high frequency in the breed. Through genotyping and informed breeding practices, the prevalence of canine MPS IIIB has been drastically reduced in the Schipperke population worldwide.
The Effects of Sildenafil and/or Nitroglycerin on Random-pattern Skin Flaps After Nicotine Application in Rats
Authors: Ellabban Mohamed A. , Fattah Islam Omar Abdel , Kader Ghada Abdel , Eldeen Omar Salah , Mehana Amir E. , Khodeer Dina M. , Hosny Hossam , Elbasiouny Mahmoud S. , Masadeh Suhail
Published: February 2020

Smoking aggravates skin necrosis as a complication of random-pattern flap ischaemia. Sildenafil and nitroglycerin (NTG) are vasodilator agents that may affect skin flap survival. Fifty rats were subjected to a dorsal random-pattern flap operation and randomly divided into 5 groups. The control group received no treatment. The ischaemic group were administered local nicotine injections. The sildenafil group were administered oral sildenafil treatment in addition to the same intervention as the ischaemic group. The NTG group received topical NTG ointment application instead of sildenafil. The combined group were given both sildenafil and NTG treatments. After 7 days, all rats were sacrificed for flap assessment. Flap survival percentages at the 3rd and 7th days were significantly higher in the combined group than in the other study groups. Histologically, the ischaemic group exhibited dermal disorganization and inflammatory cell infiltration, which were improved in the 3 treated groups; however, the combined group presented the most relevant effect. The epidermal thickness showed a decrease in the ischaemic group (23.1 μm) that was significantly increased in the sildenafil (28.4 μm), NTG (28.8 μm) and combined (35.8 μm) groups. Immunohistochemically, the combined group exhibited a significant decrease in the apoptotic index and an increase in the proliferative index (2.3 and 56.9%, respectively) compared to those in the ischaemic (63.2 and 3%), sildenafil (41.7 and 28.1%) and NTG (39.3 and 30.4%) groups. Transmission electron microscopy (TEM) showed that the combined group displayed improvement in most of the ischaemic changes. Our analyses suggest that the combined use of sildenafil and NTG is more efficacious than using only one of these treatments for skin flap survival.
Upper Airway Obstruction Elicited Energy Imbalance Leads to Growth Retardation that Persists after the Obstruction Removal
Authors: Assadi Mohammad H. , Segev Yael , Tarasiuk Ariel
Published: February 2020

Upper airway obstruction can lead to growth retardation by unclear mechanisms. We explored the effect of upper airway obstruction in juvenile rats on whole-body energy balance, growth plate metabolism, and growth. We show that after seven weeks, obstructed animals’ ventilation during room air breathing increased, and animals grew less due to abnormal growth plate metabolism. Increased caloric intake in upper airway-obstructed animals did not meet increased energy expenditure associated with increased work of breathing. Decreased whole-body energy balance induced hindrance of bone elongation following obstruction removal, and array pathways regulating growth plate development and marrow adiposity. This is the first study to show that rapidly growing animals cannot consume enough calories to maintain their energy homeostasis, leading to an impediment in growth in the effort to save energy.
Author Correction: Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes
Authors: Li Xian , Lee Youn Ju , Jin Fansi , Park Young Na , Deng Yifeng , Kang Youra , Yang Ju Hye , Chang Jae-Hoon , Kim Dong-Young , Kim Jung-Ae , Chang Young-Chae , Ko Hyun-Jeong , Kim Cheorl-Ho , Murakami Makoto , Chang Hyeun Wook
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan
Authors: Hsu Chih-Hsiung , Hsiao Cheng-Wen , Sun Chien-An , Wu Wen-Chih , Yang Tsan , Hu Je-Ming , Liao Yu-Chan , Huang Chi-Hua , Chen Chao-Yang , Lin Fu-Huang , Chou Yu-Ching
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Pain perception during social interactions is modulated by self-related and moral contextual cues
Authors: Nicolardi Valentina , Panasiti Maria Serena , D’Ippolito Mariagrazia , Pecimo Gian Luigi , Aglioti Salvatore Maria
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Sensitive and specific detection of tumour cells based on a multivalent DNA nanocreeper and a multiplexed fluorescence supersandwich
Authors: Luo Lei , Li Wenshan , Xiang Dongliu , Ma Yanyun , Zhou Yuan , Xu Yaqing , Chen Nandi , Wang Qing , Huang Jin , Liu Jianbo , Yang Xiaohai , Wang Kemin
Published: February 2020

A self-assembled DNA nanostructure with improved binding affinity and fluorescence signal was developed for low abundance target cell detection.
Donkey milk inhibits triple-negative breast tumor progression and is associated with increased cleaved-caspase-3 expression
Authors: Li Qilong , Li Mohan , Zhang Juan , Shi Xinyang , Yang Mei , Zheng Yan , Cao Xueyan , Yue Xiqing , Ma Shiliang
Published: February 2020

Donkey milk is considered an ideal substitute for human milk and is considered a potential complementary dairy product for the treatment of a variety of human diseases, including cancer.
Fe2CS2 MXene: a promising electrode for Al-ion batteries
Authors: Lee Sangjin , Jung Sung Chul , Han Young-Kyu
Published: February 2020

Using late transition metals and sulfur termination groups for MXene leads to 104-fold increase in Al-ion transport and 2.2-fold increase in Al-ion capacity, respectively.
Rapid and mass-producible synthesis of high-crystallinity MoSe2 nanosheets by ampoule-loaded chemical vapor deposition
Authors: Liu Na , Choi Woong , Kim Hyeongi , Jung Chulseung , Kim Jeonghun , Choo Soo Ho , Kwon Yena , An Byeong-Seon , Hong Seongin , So Seongjoon , Yang Cheol-Woong , Hur Jaehyun , Kim Sunkook
Published: February 2020

Rapid growth of high-crystalline MoSe2 nanosheets with grain size of up to ∼100 μm and yield of milligrams per hour.
Effective estimation of the inhibitor affinity of HIV-1 proteaseviaa modified LIE approach
Authors: Ngo Son Tung , Hong Nam Dao , Quynh Anh Le Huu , Hiep Dinh Minh , Tung Nguyen Thanh
Published: February 2020

The inhibition of the Human Immunodeficiency Virus Type 1 Protease (HIV-1 PR) can prevent the synthesis of new viruses.
The effect of size and surface ligands of iron oxide nanoparticles on blood compatibility
Authors: Liu Tao , Bai Ru , Zhou Huige , Wang Rongqi , Liu Jing , Zhao Yuliang , Chen Chunying
Published: February 2020

Due to the unique physicochemical properties, superparamagnetic iron oxide nanoparticles (SPIONs) have attracted increased attention, which show different effects on red blood cell, plasma, platelet, C3 complement and vascular endothelial cell.