bluuebunny/crossref_metadata_2025 huggingface dataset:
LMCD1 promotes osteogenic differentiation of human bone marrow stem cells by regulating BMP signaling
Authors: Zhu Bin , Xue Feng , Zhang Changqing , Li Guangyi
Published: September 2019

Human bone marrow stem cells (BMSCs) are heterogeneous progenitor cells with two defining features, self-renew and multi-lineage differentiation. As one of the differentiation directions, osteogenesis is vital for bone homeostasis. A growing body of evidences show that ubiquitin-dependent protein degradation plays an essential role in the osteogenic differentiation of BMSCs. In this study, we found that LMCD1 was upregulated during osteogenic differentiation process of BMSCs by analyzing GSE80614. In vitro and in vivo functional studies confirmed that LMCD1 was critical to the osteogenic commitment of BMSCs. Compared to those of the controls, downregulation of LMCD1 significantly restrained osteogenic differentiation and enhanced adipogenic differentiation, while upregulation of LMCD1 increased the osteogenic differentiation and suppressed adipogenic differentiation. Mechanically, we found that LMCD1 could protect RUNX2 and Smad1 protein from Smurf1-induced ubiquitination degradation thereby regulating BMP signaling. In conclusion, our findings suggest that LMCD1 is a novel regulator of osteogenic differentiation and may be a potential therapeutic target for bone metabolism related diseases.
The role of pyroptosis in cancer: pro-cancer or pro-“host”?
Authors: Xia Xiaojing , Wang Xin , Cheng Zhe , Qin Wanhai , Lei Liancheng , Jiang Jinqing , Hu Jianhe
Published: September 2019

Programmed cell death (PCD) refers to the way in which cells die depending on specific genes encoding signals or activities. Apoptosis, autophagy, and pyroptosis are all mechanisms of PCD. Among these mechanisms, pyroptosis is mediated by the gasdermin family, accompanied by inflammatory and immune responses. The relationship between pyroptosis and cancer is complex, and the effects of pyroptosis on cancer vary in different tissues and genetic backgrounds. On one hand, pyroptosis can inhibit the occurrence and development of tumors; on the other hand, as a type of proinflammatory death, pyroptosis can form a suitable microenvironment for tumor cell growth and thus promote tumor growth. In addition, the induction of tumor pyroptosis is also considered a potential cancer treatment strategy. Studies have shown that DFNA5 (nonsyndromic hearing impairment protein 5)/GSDME (Gasdermin-E) mRNA methylation results in lower expression levels of DFNA5/GSDME in most tumor cells than in normal cells, making it difficult to activate the pyroptosis in most tumor cells. During the treatment of malignant tumors, appropriate chemotherapeutic drugs can be selected according to the expression levels of DFNA5/GSDME, which can be upregulated in tumor cells, thereby increasing the sensitivity to chemotherapeutic drugs and reducing drug resistance. Therefore, induced pyroptosis may play a predominant role in the treatment of cancer. Here, we review the latest research on the anti- and protumor effects of pyroptosis and its potential applications in cancer treatment.
Dominant role of splenic marginal zone lipid rafts in the classical complement pathway against S. pneumoniae
Authors: Yang Seung Woo , Park Jin-Yeon , Choi Hyeongjwa , Yun Tae Jin , Choi Woo-Sung , Kim Min-Kyung , Lee Yun Kyung , Park Min , Jin Yihwa , Joo Jin Soo , Choi In-Soo , Park Seung Hwa , Hwang Han Sung , Kang Young-Sun
Published: September 2019

Lipid rafts (LRs) play crucial roles in complex physiological processes, modulating innate and acquired immune responses to pathogens. The transmembrane C-type lectins human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and its mouse homolog SIGN-R1 are distributed in LRs and expressed on splenic marginal zone (MZ) macrophages. The DC-SIGN-C1q or SIGN-R1-C1q complex could mediate the immunoglobulin (Ig)-independent classical complement pathway againstStreptococcus pneumoniae. Precise roles of LRs during this complement pathway are unknown. Here we show that LRs are indispensable for accelerating the DC-SIGN- or SIGN-R1-mediated classical complement pathway againstS. pneumoniae, thus facilitating rapid clearance of the pathogen. The trimolecular complex of SIGN-R1-C1q-C4 was exclusively enriched in LRs of splenic MZ macrophages and their localization was essential for activating C3 catabolism and enhancing pneumococcal clearance, which were abolished in SIGN-R1-knockout mice. However, DC-SIGN replacement on splenic MZ macrophage’s LRs of SIGN-R1-depleted mice reversed these defects. Disruption of LRs dramatically reduced pneumococcal uptake and decomposition. Additionally, DC- SIGN, C1q, C4, and C3 were obviously distributed in splenic LRs of cadavers. Therefore, LRs on splenic SIGN-R1+or DC-SIGN+macrophages could provide spatially confined and optimal bidirectional platforms, not only for usual intracellular events, for example recognition and phagocytosis of pathogens, but also an unusual extracellular event such as the complement system. These findings improve our understanding of the orchestrated roles of the spleen, unraveling a new innate immune system initiated from splenic MZ LRs, and yielding answers to several long-standing problems, including the need to understand the profound role of LRs in innate immunity, the need to identify how such a small portion of splenic SIGN-R1+macrophages (<0.05% of splenic macrophages) effectively resistS. pneumoniae, and the need to understand how LRs can promote the protective function of DC-SIGN againstS. pneumoniaein the human spleen.
Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing
Authors: Zeng Yang , He Jian , Bai Zhijie , Li Zongcheng , Gong Yandong , Liu Chen , Ni Yanli , Du Junjie , Ma Chunyu , Bian Lihong , Lan Yu , Liu Bing
Published: September 2019

Tracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to the technical limitations and the material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (HECs) were captured at Carnegie stage (CS) 12–14 in an unbiased way, showing an unambiguous feature of arterial endothelial cells (ECs) with the up-regulation ofRUNX1,MYBandANGPT1. Importantly, subcategorizing CD34+CD45−ECs into a CD44+population strikingly enriched HECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed HECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, includingEMCN,PROCRandRUNX1T1. We also uncovered another temporally and molecularly distinct intra-embryonic HEC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed HECs. The cellular and molecular programs that underlie the generation of the first HSCs from HECs in human embryos, together with the ability to distinguish the HSC-primed HECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.
Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas
Authors: Komura Shingo , Ito Kenji , Ohta Sho , Ukai Tomoyo , Kabata Mio , Itakura Fumiaki , Semi Katsunori , Matsuda Yutaka , Hashimoto Kyoichi , Shibata Hirofumi , Sone Masamitsu , Jo Norihide , Sekiguchi Kazuya , Ohno Takatoshi , Akiyama Haruhiko , Shimizu Katsuji , Woltjen Knut , Ozawa Manabu , Toguchida Junya , Yamamoto Takuya , Yamada Yasuhiro
Published: September 2019

Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.
Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice
Authors: Figueiredo Claudia P. , Barros-Aragão Fernanda G. Q. , Neris Rômulo L. S. , Frost Paula S. , Soares Carolina , Souza Isis N. O. , Zeidler Julianna D. , Zamberlan Daniele C. , de Sousa Virginia L. , Souza Amanda S. , Guimarães André Luis A. , Bellio Maria , Marcondes de Souza Jorge , Alves-Leon Soniza V. , Neves Gilda A. , Paula-Neto Heitor A. , Castro Newton G. , De Felice Fernanda G. , Assunção-Miranda Iranaia , Clarke Julia R. , Da Poian Andrea T. , Ferreira Sergio T.
Published: September 2019

Neurological complications affecting the central nervous system have been reported in adult patients infected by Zika virus (ZIKV) but the underlying mechanisms remain unknown. Here, we report that ZIKV replicates in human and mouse adult brain tissue, targeting mature neurons. ZIKV preferentially targets memory-related brain regions, inhibits hippocampal long-term potentiation and induces memory impairment in adult mice. TNF-α upregulation, microgliosis and upregulation of complement system proteins, C1q and C3, are induced by ZIKV infection. Microglia are found to engulf hippocampal presynaptic terminals during acute infection. Neutralization of TNF-α signaling, blockage of microglial activation or of C1q/C3 prevent synapse and memory impairment in ZIKV-infected mice. Results suggest that ZIKV induces synapse and memory dysfunction via aberrant activation of TNF-α, microglia and complement. Our findings establish a mechanism by which ZIKV affects the adult brain, and point to the need of evaluating cognitive deficits as a potential comorbidity in ZIKV-infected adults.
Unveiling hidden multipolar orders with magnetostriction
Authors: Patri Adarsh S. , Sakai Akito , Lee SungBin , Paramekanti Arun , Nakatsuji Satoru , Kim Yong Baek
Published: September 2019

Broken symmetries in solids involving higher order multipolar degrees of freedom are historically referred to as “hidden orders” due to the formidable task of detecting them with conventional probes. In this work, we theoretically propose that magnetostriction provides a powerful and novel tool to directly detect higher-order multipolar symmetry breaking—such as the elusive octupolar order—by examining scaling behaviour of length change with respect to an applied magnetic field h. Employing a symmetry-based Landau theory, we focus on the family of Pr-based cage compounds with strongly correlated f-electrons, Pr(Ti,V,Ir)2(Al,Zn)20, whose low energy degrees of freedom are purely higher-order multipoles: quadrupoles $${\cal{O}}_{20,22}$$

O

20
,
22

and octupole $${\cal{T}}_{xyz}$$

T

x
y
z

. We demonstrate that a magnetic field along the [111] direction induces a distinct linear-in-h length change below the octupolar ordering temperature. The resulting “magnetostriction coefficient” is directly proportional to the octupolar order parameter, thus providing clear access to such subtle order parameters.
Environmental temperatures shape thermal physiology as well as diversification and genome-wide substitution rates in lizards
Authors: Garcia-Porta Joan , Irisarri Iker , Kirchner Martin , Rodríguez Ariel , Kirchhof Sebastian , Brown Jason L. , MacLeod Amy , Turner Alexander P. , Ahmadzadeh Faraham , Albaladejo Gonzalo , Crnobrnja-Isailovic Jelka , De la Riva Ignacio , Fawzi Adnane , Galán Pedro , Göçmen Bayram , Harris D. James , Jiménez-Robles Octavio , Joger Ulrich , Jovanović Glavaš Olga , Karış Mert , Koziel Giannina , Künzel Sven , Lyra Mariana , Miles Donald , Nogales Manuel , Oğuz Mehmet Anıl , Pafilis Panayiotis , Rancilhac Loïs , Rodríguez Noemí , Rodríguez Concepción Benza , Sanchez Eugenia , Salvi Daniele , Slimani Tahar , S’khifa Abderrahim , Qashqaei Ali Turk , Žagar Anamarija , Lemmon Alan , Moriarty Lemmon Emily , Carretero Miguel Angel , Carranza Salvador , Philippe Hervé , Sinervo Barry , Müller Johannes , Vences Miguel , Wollenberg Valero Katharina C.
Published: September 2019

Climatic conditions changing over time and space shape the evolution of organisms at multiple levels, including temperate lizards in the family Lacertidae. Here we reconstruct a dated phylogenetic tree of 262 lacertid species based on a supermatrix relying on novel phylogenomic datasets and fossil calibrations. Diversification of lacertids was accompanied by an increasing disparity among occupied bioclimatic niches, especially in the last 10 Ma, during a period of progressive global cooling. Temperate species also underwent a genome-wide slowdown in molecular substitution rates compared to tropical and desert-adapted lacertids. Evaporative water loss and preferred temperature are correlated with bioclimatic parameters, indicating physiological adaptations to climate. Tropical, but also some populations of cool-adapted species experience maximum temperatures close to their preferred temperatures. We hypothesize these species-specific physiological preferences may constitute a handicap to prevail under rapid global warming, and contribute to explaining local lizard extinctions in cool and humid climates.
Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction
Authors: Giannoudaki Eirini , Hernandez-Santana Yasmina E. , Mulfaul Kelly , Doyle Sarah L. , Hams Emily , Fallon Padraic G. , Mat Arimin , O’Shea Donal , Kopf Manfred , Hogan Andrew E. , Walsh Patrick T.
Published: September 2019

Members of the interleukin-1 (IL-1) family are important mediators of obesity and metabolic disease and have been described to often play opposing roles. Here we report that the interleukin-36 (IL-36) subfamily can play a protective role against the development of disease. Elevated IL-36 cytokine expression is found in the serum of obese patients and negatively correlates with blood glucose levels among those presenting with type 2 diabetes. Mice lacking IL-36Ra, an IL-36 family signalling antagonist, develop less diet-induced weight gain, hyperglycemia and insulin resistance. These protective effects correlate with increased abundance of the metabolically protective bacteria Akkermansia muciniphila in the intestinal microbiome. IL-36 cytokines promote its outgrowth as well as increased colonic mucus secretion. These findings identify a protective role for IL-36 cytokines in obesity and metabolic disease, adding to the current understanding of the role the broader IL-1 family plays in regulating disease pathogenesis.
Tracking the ultrafast motion of an antiferromagnetic order parameter
Authors: Tzschaschel Christian , Satoh Takuya , Fiebig Manfred
Published: September 2019

The unique functionalities of antiferromagnets offer promising routes to advance information technology. Their compensated magnetic order leads to spin resonances in the THz-regime, which suggest the possibility to coherently control antiferromagnetic (AFM) devices orders of magnitude faster than traditional electronics. However, the required time resolution, complex sublattice interactions and the relative inaccessibility of the AFM order parameter pose serious challenges to studying AFM spin dynamics. Here, we reveal the temporal evolution of an AFM order parameter directly in the time domain. We modulate the AFM order in hexagonal YMnO3 by coherent magnon excitation and track the ensuing motion of the AFM order parameter using time-resolved optical second-harmonic generation. The dynamic symmetry reduction by the moving order parameter allows us to separate electron dynamics from spin dynamics. As transient symmetry reductions are common to coherent excitations, we have a general tool for tracking the ultrafast motion of an AFM order parameter.
Giant oscillations in a triangular network of one-dimensional states in marginally twisted graphene
Authors: Xu S. G. , Berdyugin A. I. , Kumaravadivel P. , Guinea F. , Krishna Kumar R. , Bandurin D. A. , Morozov S. V. , Kuang W. , Tsim B. , Liu S. , Edgar J. H. , Grigorieva I. V. , Fal’ko V. I. , Kim M. , Geim A. K.
Published: September 2019

At very small twist angles of ∼0.1°, bilayer graphene exhibits a strain-accompanied lattice reconstruction that results in submicron-size triangular domains with the standard, Bernal stacking. If the interlayer bias is applied to open an energy gap inside the domain regions making them insulating, such marginally twisted bilayer graphene is expected to remain conductive due to a triangular network of chiral one-dimensional states hosted by domain boundaries. Here we study electron transport through this helical network and report giant Aharonov-Bohm oscillations that reach in amplitude up to 50% of resistivity and persist to temperatures above 100 K. At liquid helium temperatures, the network exhibits another kind of oscillations that appear as a function of carrier density and are accompanied by a sign-changing Hall effect. The latter are attributed to consecutive population of the narrow minibands formed by the network of one-dimensional states inside the gap.
Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids
Authors: Miyamoto Junki , Igarashi Miki , Watanabe Keita , Karaki Shin-ichiro , Mukouyama Hiromi , Kishino Shigenobu , Li Xuan , Ichimura Atsuhiko , Irie Junichiro , Sugimoto Yukihiko , Mizutani Tetsuya , Sugawara Tatsuya , Miki Takashi , Ogawa Jun , Drucker Daniel J. , Arita Makoto , Itoh Hiroshi , Kimura Ikuo
Published: September 2019

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.
Thermal cues drive plasticity of desiccation resistance in montane salamanders with implications for climate change
Authors: Riddell Eric A. , Roback Emma Y. , Wells Christina E. , Zamudio Kelly R. , Sears Michael W.
Published: September 2019

Organisms rely upon external cues to avoid detrimental conditions during environmental change. Rapid water loss, or desiccation, is a universal threat for terrestrial plants and animals, especially under climate change, but the cues that facilitate plastic responses to avoid desiccation are unclear. We integrate acclimation experiments with gene expression analyses to identify the cues that regulate resistance to water loss at the physiological and regulatory level in a montane salamander (Plethodon metcalfi). Here we show that temperature is an important cue for developing a desiccation-resistant phenotype and might act as a reliable cue for organisms across the globe. Gene expression analyses consistently identify regulation of stem cell differentiation and embryonic development of vasculature. The temperature-sensitive blood vessel development suggests that salamanders regulate water loss through the regression and regeneration of capillary beds in the skin, indicating that tissue regeneration may be used for physiological purposes beyond replacing lost limbs.
Translational coupling via termination-reinitiation in archaea and bacteria
Authors: Huber Madeleine , Faure Guilhem , Laass Sebastian , Kolbe Esther , Seitz Kristina , Wehrheim Christina , Wolf Yuri I. , Koonin Eugene V. , Soppa Jörg
Published: September 2019

The genomes of many prokaryotes contain substantial fractions of gene pairs with overlapping stop and start codons (ATGA or TGATG). A potential benefit of overlapping gene pairs is translational coupling. In 720 genomes of archaea and bacteria representing all major phyla, we identify substantial, albeit highly variable, fractions of co-directed overlapping gene pairs. Various patterns are observed for the utilization of the SD motif for de novo initiation at upstream genes versus reinitiation at overlapping gene pairs. We experimentally test the predicted coupling in 9 gene pairs from the archaeonHaloferax volcaniiand 5 gene pairs from the bacteriumEscherichia coli. In 13 of 14 cases, translation of both genes is strictly coupled. Mutational analysis of SD motifs located upstream of the downstream genes indicate that the contribution of the SD to translational coupling widely varies from gene to gene. The nearly universal, abundant occurrence of overlapping gene pairs suggests that tight translational coupling is widespread in archaea and bacteria.
Hippocampal-neocortical interactions sharpen over time for predictive actions
Authors: Hindy Nicholas C. , Avery Emily W. , Turk-Browne Nicholas B.
Published: September 2019

When an action is familiar, we are able to anticipate how it will change the state of the world. These expectations can result from retrieval of action-outcome associations in the hippocampus and the reinstatement of anticipated outcomes in visual cortex. How does this role for the hippocampus in action-based prediction change over time? We use high-resolution fMRI and a dual-training behavioral paradigm to examine how the hippocampus interacts with visual cortex during predictive and nonpredictive actions learned either three days earlier or immediately before the scan. Just-learned associations led to comparable background connectivity between the hippocampus and V1/V2, regardless of whether actions predicted outcomes. However, three-day-old associations led to stronger background connectivity and greater differentiation between neural patterns for predictive vs. nonpredictive actions. Hippocampal prediction may initially reflect indiscriminate binding of co-occurring events, with action information pruning weaker associations and leading to more selective and accurate predictions over time.
Multi-stimuli-responsive programmable biomimetic actuator
Authors: Dong Yue , Wang Jie , Guo Xukui , Yang Shanshan , Ozen Mehmet Ozgun , Chen Peng , Liu Xin , Du Wei , Xiao Fei , Demirci Utkan , Liu Bi-Feng
Published: September 2019

Untethered small actuators have various applications in multiple fields. However, existing small-scale actuators are very limited in their intractability with their surroundings, respond to only a single type of stimulus and are unable to achieve programmable structural changes under different stimuli. Here, we present a multiresponsive patternable actuator that can respond to humidity, temperature and light, via programmable structural changes. This capability is uniquely achieved by a fast and facile method that was used to fabricate a smart actuator with precise patterning on a graphene oxide film by hydrogel microstamping. The programmable actuator can mimic the claw of a hawk to grab a block, crawl like an inchworm, and twine around and grab the rachis of a flower based on their geometry. Similar to the large- and small-scale robots that are used to study locomotion mechanics, these small-scale actuators can be employed to study movement and biological and living organisms.
Bridging of Neisseria gonorrhoeae lineages across sexual networks in the HIV pre-exposure prophylaxis era
Authors: Williamson Deborah A. , Chow Eric P. F. , Gorrie Claire L. , Seemann Torsten , Ingle Danielle J. , Higgins Nasra , Easton Marion , Taiaroa George , Grad Yonatan H. , Kwong Jason C. , Fairley Christopher K. , Chen Marcus Y. , Howden Benjamin P.
Published: September 2019

Whole genome sequencing (WGS) has been used to investigate transmission of Neisseria gonorrhoeae, but to date, most studies have not combined genomic data with detailed information on sexual behaviour to define the extent of transmission across population risk groups (bridging). Here, through combined epidemiological and genomic analysis of 2,186N. gonorrhoeae isolates from Australia, we show widespread transmission of N. gonorrhoeae within and between population groups. We describe distinct transmission clusters associated with men who have sex with men (MSM) and heterosexuals, and men who have sex with men and women (MSMW) are identified as a possible bridging population between these groups. Further, the study identifies transmission of N. gonorrhoeae between HIV-positive and HIV-negative individuals receiving pre-exposure prophylaxis (PrEP). Our data highlight several groups that can be targeted for interventions aimed at improving gonorrhoea control, including returning travellers, sex workers, and PrEP users.
Comparative genomics reveals the origin of fungal hyphae and multicellularity
Authors: Kiss Enikő , Hegedüs Botond , Virágh Máté , Varga Torda , Merényi Zsolt , Kószó Tamás , Bálint Balázs , Prasanna Arun N. , Krizsán Krisztina , Kocsubé Sándor , Riquelme Meritxell , Takeshita Norio , Nagy László G.
Published: September 2019

Hyphae represent a hallmark structure of multicellular fungi. The evolutionary origins of hyphae and of the underlying genes are, however, hardly known. By systematically analyzing 72 complete genomes, we here show that hyphae evolved early in fungal evolution probably via diverse genetic changes, including co-option and exaptation of ancient eukaryotic (e.g. phagocytosis-related) genes, the origin of new gene families, gene duplications and alterations of gene structure, among others. Contrary to most multicellular lineages, the origin of filamentous fungi did not correlate with expansions of kinases, receptors or adhesive proteins. Co-option was probably the dominant mechanism for recruiting genes for hypha morphogenesis, while gene duplication was apparently less prevalent, except in transcriptional regulators and cell wall - related genes. We identified 414 novel gene families that show correlated evolution with hyphae and that may have contributed to its evolution. Our results suggest that hyphae represent a unique multicellular organization that evolved by limited fungal-specific innovations and gene duplication but pervasive co-option and modification of ancient eukaryotic functions.
p97 regulates GluA1 homomeric AMPA receptor formation and plasma membrane expression
Authors: Ge Yuan , Tian Meng , Liu Lidong , Wong Tak Pan , Gong Bo , Wu Dongchuan , Cho Taesup , Lin Shujun , Kast Jürgen , Lu Jie , Wang Yu Tian
Published: September 2019

The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors (AMPARs) mediate the fast excitatory synaptic transmission in the mammalian brain and are important for synaptic plasticity. In particular, the rapid insertion of the GluA1 homomeric (GluA1-homo) AMPARs into the postsynaptic membrane is considered to be critical in the expression of hippocampal CA1 long-term potentiation (LTP), which is important for certain forms of learning and memory. However, how the formation and trafficking of GluA1-homo AMPARs are regulated remains poorly understood. Here, we report that p97 specifically interacts with and promotes the formation of GluA1-homo AMPARs. The association with p97 retains GluA1-homo AMPARs in the intracellular compartment under basal conditions, and its dissociation allows GluA1-homo AMPARs to be rapidly inserted into the postsynaptic membrane shortly after LTP induction. Thus, our results shed lights into the molecular mechanisms by which p97 regulates GluA1-homo AMPARs formation and trafficking, thereby playing a critical role in mediating synaptic plasticity.
Muscarinic acetylcholine receptor signaling generates OFF selectivity in a simple visual circuit
Authors: Qin Bo , Humberg Tim-Henning , Kim Anna , Kim Hyong S. , Short Jacob , Diao Fengqiu , White Benjamin H. , Sprecher Simon G. , Yuan Quan
Published: September 2019

ON and OFF selectivity in visual processing is encoded by parallel pathways that respond to either light increments or decrements. Despite lacking the anatomical features to support split channels, Drosophila larvae effectively perform visually-guided behaviors. To understand principles guiding visual computation in this simple circuit, we focus on investigating the physiological properties and behavioral relevance of larval visual interneurons. We find that the ON vs. OFF discrimination in the larval visual circuit emerges through light-elicited cholinergic signaling that depolarizes a cholinergic interneuron (cha-lOLP) and hyperpolarizes a glutamatergic interneuron (glu-lOLP). Genetic studies further indicate that muscarinic acetylcholine receptor (mAchR)/Gαo signaling produces the sign-inversion required for OFF detection in glu-lOLP, the disruption of which strongly impacts both physiological responses of downstream projection neurons and dark-induced pausing behavior. Together, our studies identify the molecular and circuit mechanisms underlying ON vs. OFF discrimination in the Drosophila larval visual system.
Low-carbon innovation induced by emissions trading in China
Authors: Zhu Junming , Fan Yichun , Deng Xinghua , Xue Lan
Published: September 2019

Emissions trading scheme (ETS) has been adopted by an increasing number of countries and regions for carbon mitigation, but its actual effect depends on specific program design and institutional context. Before launching the world largest ETS, China experimented with seven independent regional pilots, whose effects are only indirectly explored. Here we provide firm-level evidence of the innovation effect directly from China’s pilot emissions trading, based on latest patenting information and a quasi-experimental design. China’s pilots increase low-carbon innovation of ETS firms by 5–10% without crowding out their other technology innovation. The increase from ETS firms accounts for about 1% increase of the regional low-carbon patents, while a similar increase from large non-ETS firms is also induced by the ETS. Most importantly, the effect is not associated with permit price, auction, or firm characteristics, but is driven by mass-based allowance allocation. A rate-based approach, however, is adopted by China’s national market.
Definition of ideal configuration for femoral neck screw fixation in older people
Authors: Guo Jialiang , Dong Weichong , Qin Shiji , Zhang Yingze
Published: September 2019

Femoral neck fractures are the most common injuries encountered by older individuals, and they are associated with high mortality and morbidity. Internal fixation to femoral neck fracture with cannulated screws placed with a configuration of an inverted triangle remain a feasible and effective treatment for femoral neck fractures. The objection of this research was to evaluate the femoral neck morphology, especially the shape of the femoral neck in Chinese people to find the optimal screw position and interval between the screws. 96 consecutive normal subjects without any previous proximal femur operation were reviewed. The patients’ information were collected from our database. The minimum of neck canal height (NCHM), neck canal width (NCWM) and inclination angle (AIA and PIA) were measured in different level. There was a significant difference between the AIA and PIA, neck canal height at inferior and superior 1/3 on posterior wall (NCHIP and NCHSP). Although there was a significant difference between the neck canal height at inferior and superior 1/3 on anterior wall (NCHIA and NCHSA, p < 0.001), but the changes were small. The shape of the anterior wall was perpendicular to the horizon and almost parallel with the FNA. In contrast, the shape of the posterior wall resembled a reverse question mark. The inverse triangular fixation was in accordance with the morphology of the femoral neck, and triangular fixation had a high risk of perforation, which may lead to nonunion and avascular necrosis. The anterior screw can be inserted easily with the help of a C-ARM, and the posterior screw positioned mildly posterior to the femoral shaft axis is recommended.
Silver ions promote blebs growth in U251 glioblastoma cell by activating nonselective cationic currents
Authors: Ragonese Francesco , Monarca Lorenzo , Bastioli Federica , Arcuri Cataldo , Mancinelli Loretta , Fioretti Bernard
Published: September 2019

Glioblastoma (GBM) is the most common and aggressive human brain cancer with low prognosis and therefore the discovery of new anticancer agents is needful. Sulfydryl reagents, such as silver, have been shown to induce membrane vesiculation in several cellular models through a mechanism that has not been yet completely clarified. Using U251 glioblastoma cells, we observed that silver induced irreversible bleb formation of the plasma membrane. This morphological event was anticipated by an increase of intracellular Ca2+ associated to extracellular Ca2+ influx. Accordingly, using patch-clamp whole cell recording during silver ion application, inward current/s (IAg) at −90 mV were detected and cells were permeable to Ca2+ and monovalent ions such as Na+. IAg activation and the intracellular Ca2+ increase promoted by silver ions (Ag+) were prevented by co-application of 20 µM cysteine and 300 µM DIDS (4,4′-Diisothiocyanatostilbene-2,2′-disulfonic acid), suggesting a critical role of thiol groups in the biological effects of silver ions. IAg was partially inhibited by 1 mM Gd3+, an unspecific inhibitor of cationic currents. Cysteine, Gd3+ and extracellular free Ca2+ solution completely abolished blebbing formation promoted by Ag+. Furthermore, extracellular Na+ ion replacement with TEA or an increase of extracellular tonicity by sucrose (100 mM) reduced both size and growth of membrane blebbing. Our data suggest that Ag+ promotes the formation necrotic blebs as consequence of the increase of intracellular Ca2+ and intracellular hydrostatic pressure associated to the activation of cationic currents. Since silver-induced blebs were less evident in benign glial human Müller MIO-M1 cells, silver compounds could represent new adjuvant to anticancer agents to improve GBM therapies.
Publisher Correction: On the role of ocular torsion in binocular visual matching
Authors: Hess Bernhard J. M.
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
New data on spermiogenesis and trepaxonematan axoneme in basal tapeworms (Cestoda, Caryophyllidea, Lytocestidae) parasitizing cyprinid fishes
Authors: Matoušková Martina , Bílý Tomáš , Bruňanská Magdaléna , Oros Mikuláš , Kostič Borislav , Nebesářová Jana
Published: September 2019

Monozoic caryophyllidean cestodes, intestinal parasites of cyprinid fishes, represent a group of tapeworms with an unclear evolutionary history. As spermatology may provide phylogenetically important data, the spermiogenesis and ultrastructure of the mature spermatozoon have been investigated using an integrative approach combining transmission electron microscopy, cytochemistry and electron tomography in Khawia rossittensis (Szidat, 1937). The process of spermatid formation is accompanied by the presence of ultrastructural characters not described in traditional models of spermiogenesis, e.g., apical electron-dense material, the two striated roots situated unusually opposite each other, branching of typical striated roots, an intercentriolar body comprising five electron-dense and four electron-lucent layers, rotation of both free flagella and flagellar buds to the median cytoplasmic process at 90°, and a complete proximodistal fusion. The synchronous rotation of both flagellar buds and growing free flagella is an evolutionarily linked pattern favouring the hypothesis that the Caryophyllidea are not ancestral but are secondarily derived from polyzoic forms. Electron tomography analysis has revealed a unique feature of two helicoidal tubular structures in the central electron-dense core of the axoneme of mature spermatozoon. These data provide new insights into the architecture of the 9 + ‘1’ axoneme, which is shared by male gametes of all trepaxonematan Platyhelminthes.
NaV1.2 haploinsufficiency in Scn2a knock-out mice causes an autistic-like phenotype attenuated with age
Authors: Léna Isabelle , Mantegazza Massimo
Published: September 2019

Mutations of the SCN2A gene, encoding the voltage gated sodium channel NaV1.2, have been associated to a wide spectrum of epileptic disorders ranging from benign familial neonatal-infantile seizures to early onset epileptic encephalopathies such as Ohtahara syndrome. These phenotypes may be caused by either gain-of-function or loss-of-function mutations. More recently, loss-of-function SCN2A mutations have also been identified in patients with autism spectrum disorder (ASD) without overt epileptic phenotypes. Heterozygous Scn2a knock-out mice (Scn2a+/−) may be a model of this phenotype. Because ASD develops in childhood, we performed a detailed behavioral characterization of Scn2a+/− mice comparing the juvenile/adolescent period of development and adulthood. We used tasks relevant to ASD and the different comorbidities frequently found in this disorder, such as anxiety or intellectual disability. Our data demonstrate that young Scn2a+/− mice display autistic-like phenotype associated to impaired memory and reduced reactivity to stressful stimuli. Interestingly, these dysfunctions are attenuated with age since adult mice show only communicative deficits. Considering the clinical data available on patients with loss-of-function SCN2A mutations, our results indicate that Scn2a+/− mice constitute an ASD model with construct and face validity during the juvenile/adolescent period of development. However, more information about the clinical features of adult carriers of SCN2A mutations is needed to evaluate comparatively the phenotype of adult Scn2a+/− mice.
A first experience of transduction for differentiated HepaRG cells using lentiviral technology
Authors: Pivert Adeline , Lefeuvre Caroline , Tran Cong-Tri , Baillou Claude , Durantel David , Le Guillou-Guillemette Hélène , Lemoine François M. , Lunel-Fabiani Françoise , Ducancelle Alexandra
Published: September 2019

Currently, there is a lack of systems for studying the role of hepatitis B viral proteins, such as HBeAg and HBcAg, on liver injury. It is necessary to develop an original tool in order to clarify the role of these viral proteins in hepatic stellate cell activation, and to understand the molecular mechanisms of liver injury. HepaRG are the most reliable hepatocyte-like cells for studying liver functions or disorders. In this paper, we demonstrate that the transduction of differentiated HepaRG (dHepaRG) cells can be performed successfully using lentiviral particles. The production of a functional Green Fluorescent Protein (GFP) assessed by Fluorescence Activated Cell Sorting and fluorescence microscopy is up to 16% of GFP positive cells using a multiplicity of infection (MOI) of 2.4. We demonstrate that this technology can allow the stable expression of GFP during the long lifecycle of the cell (up to four weeks after the cell’s passage). With this innovative tool, we aim to express viral proteins such as HBeAg or HBcAg in dHepaRG cells. The preliminary results of this work shows that HBeAg can be efficiently produced in dHepaRG cells and that increased MOI allows a better production of this protein. Our future objective will be to study the role of HBc and HBe proteins on the induction of hepatic fibrosis.
Laboratory and field evaluation of acetic acid-based lures for male Asian citrus psyllid, Diaphorina citri
Authors: Zanardi Odimar Z. , Volpe Haroldo X. L. , Luvizotto Rejane A. G. , Magnani Rodrigo F. , Gonzalez Francisco , Calvo Carolina , Oehlschlager Cameron A. , Lehan Benjamin J. , Esperança Victoria , Delfino Jennifer Y. , de Freitas Renato , de Carvalho Rômulo Igor , Mulinari Tatiana Aparecida , Miranda Marcelo P. , Bento José Mauricio S. , Leal Walter S.
Published: September 2019

The Asian citrus psyllid (ACP) is a vector of a pathogen associated with greening and thus a major problem in citriculture worldwide. Lures are much needed for improving ACP trapping systems for monitoring populations and surveillance. Previously, we have identified acetic acid as a putative sex pheromone and measured formic acid- and propionic acid-elicited robust electroantennographic responses. We have now thoroughly examined in indoor behavioral assays (4-way olfactometer) and field tests the feasibility of these three semiochemicals as potential lures for trapping ACP. Formic acid, acetic acid, and propionic acid at appropriate doses are male-specific attractants and suitable lures for ACP traps, but they do not act synergistically. An acetic acid-based homemade lure, prepared by impregnating the attractant in a polymer, was active for a day. A newly developed slow-release formulation had equal performance but lasted longer, thus leading to an important improvement in ACP trap capture at low population densities.
Alpha-tocopherol fertigation confers growth physio-biochemical and qualitative yield enhancement in field grown water deficit wheat (Triticum aestivum L.)
Authors: Ali Qasim , Ali Shafaqat , Iqbal Naeem , Javed Muhammad Tariq , Rizwan Muhammad , Khaliq Roubina , Shahid Sumreena , Perveen Rashida , Alamri Saud A. , Alyemeni Mohammed Nasser , Wijaya Leonard , Ahmad Parvaiz
Published: September 2019

Water stress is a major problem to fulfill the world food demand and to solve the problem of malnutrition. Different strategies are being used to solve these problems including the fertigation of plants with different biochemical at different growth stages. The present study was conducted for the induction of drought tolerance in field grown wheat for better yield and nutritional quality through foliar spray of α-tocopherol (α-Toc) at start of reproductive stage. Water stress was maintained based on number of irrigation. Three levels of α-Toc 0.001, 0.01 and 0.1 mM were applied as foliar spray. Water stress significantly reduced the biomass production that associated with the decreased photosynthetic pigments, water relation, photosynthetic efficiency, but increased the lipid peroxidation, leaf relative membrane permeability, activities of antioxidant enzymes and the contents of phenolic, flavonoids, α-toc and ASA. Water stress also negatively effected the different yield attributes and seed nutrient quality. Foliar fertigation of wheat plants with α-Toc significantly improved the water stress tolerance of wheat plants in term of improvement in growth and seed yield associated with improved water relations, photosynthetic efficiency, contents of photosynthetic pigments and improvement in antioxidative defence mechanism (enzymatic and non-enzymatic antioxidants). Fertigation of water stressed wheat plants with α-Toc also improved the seed nutritional quality in terms of the contents of seed phenolics, flavonoids, activities of antioxidant enzymes and the content of α-, β- and γ-tocopherols. In conclusion, it was found that fertigation of water stressed wheat plants not only improved the water stress tolerance but also improved the seed yield and nutritional quality that will not only be helpful for the improvement in wheat yield that also be a step to solve the problem of malnutrition through the bio-fertification of α-Toc.
A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector
Authors: Ohtsuka Junpei , Fukumura Masayuki , Furuyama Wakako , Wang Shujie , Hara Kenichiro , Maeda Mitsuyo , Tsurudome Masato , Miyamoto Hiroko , Kaito Aika , Tsuda Nobuyuki , Kataoka Yosky , Mizoguchi Akira , Takada Ayato , Nosaka Tetsuya
Published: September 2019

Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.
Analysis of nonlinear characteristics of a graphene based four-terminal ballistic rectifier using a drift-diffusion model
Authors: Garg Ankur , Jain Neelu , Kumar Sanjeev , Kasjoo Shahrir R. , Singh Arun Kumar
Published: September 2019

In this study, rectification behavior and noise spectra of a graphene based four-terminal ballistic rectifier are reported utilizing semi-classical drift-diffusion 3D modeling.
Incorporation of thermal gels for facile microfluidic transient isotachophoresis
Authors: Burton Jordan B. , Ward Cassandra L. , Klemet David M. , Linz Thomas H.
Published: September 2019

Thermal gels uniquely lock distinct solutions into place to facilitate user-friendly transient isotachophoresis analyses.
Surface acidity enhancement of CeO2 catalysts via modification with a heteropoly acid for the selective catalytic reduction of NO with ammonia
Authors: Ke Yu , Huang Wenjun , Li Sichao , Liao Yong , Li Jiaxing , Qu Zan , Yan Naiqiang
Published: September 2019

The surface acidity enhanced CeO2 catalysts exhibited a SCR reaction path that both mechanisms existed but E-R dominated.
Dioxygen controls the nitrosylation reactions of a protein-bound [4Fe4S] cluster
Authors: Grabarczyk Daniel B. , Ash Philip A. , Myers William K. , Dodd Erin L. , Vincent Kylie A.
Published: September 2019

Iron–sulfur clusters are exceptionally tuneable protein cofactors, and as one of their many roles they are involved in biological responses to nitrosative stress.
Inter-ligand delocalisations in transition metal complexes containing multiple non-innocent ligands
Authors: Wan Ho Chuen , Zhang Jing-Xuan , Leung Chung Sum , Sheong Fu Kit , Lin Zhenyang
Published: September 2019

Inter-ligand delocalisation across the metal centre has been identified in a number of coordination complexes and systematically investigated with the help of PIO analysis.
Symmetry breaking structural phase transitions, dielectric properties and molecular motions of formamidinium cations in 1D and 2D hybrid compounds: (NH2CHNH2)3[Bi2Cl9] and (NH2CHNH2)3[Bi2Br9]
Authors: Mencel K. , Starynowicz P. , Siczek M. , Piecha-Bisiorek A. , Jakubas R. , Medycki W.
Published: September 2019

Two organic–inorganic hybrid halobismuthates(iii), (NH2CHNH2)3[Bi2Cl9] (FBC) and (NH2CHNH2)3[Bi2Br9] (FBB), have been prepared with their structures revealed by single-crystal X-ray diffraction at various temperatures.
Novel synthesis of a NiMoP phosphide catalyst in a CH4–CO2 gas mixture
Authors: Li Zhichao , Liu Qingyou , Shi Yan , Yao Zhiwei , Ding Wei , Sun Yue
Published: September 2019

NiMo bimetallic phosphide was synthesized from its corresponding oxidic precursor in a 1 : 1 CH4 : CO2 gas mixture for the first time.