bluuebunny/crossref_metadata_2025_split huggingface dataset:
A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy
Authors: Nikopoulos Konstantinos , Cisarova Katarina , Quinodoz Mathieu , Koskiniemi-Kuendig Hanna , Miyake Noriko , Farinelli Pietro , Rehman Atta Ur , Khan Muhammad Imran , Prunotto Andrea , Akiyama Masato , Kamatani Yoichiro , Terao Chikashi , Miya Fuyuki , Ikeda Yasuhiro , Ueno Shinji , Fuse Nobuo , Murakami Akira , Wada Yuko , Terasaki Hiroko , Sonoda Koh-Hei , Ishibashi Tatsuro , Kubo Michiaki , Cremers Frans P. M. , Kutalik Zoltán , Matsumoto Naomichi , Nishiguchi Koji M. , Nakazawa Toru , Rivolta Carlo 
Published: June 2019

AbstractHereditary retinal degenerations (HRDs) are Mendelian diseases characterized by progressive blindness and caused by ultra-rare mutations. In a genomic screen of 331 unrelated Japanese patients, we identify a disruptive Alu insertion and a nonsense variant (p.Arg1933*) in the ciliary gene RP1, neither of which are rare alleles in Japan. p.Arg1933* is almost polymorphic (frequency = 0.6%, amongst 12,000 individuals), does not cause disease in homozygosis or heterozygosis, and yet is significantly enriched in HRD patients (frequency = 2.1%, i.e., a 3.5-fold enrichment; p-value = 9.2 × 10−5). Familial co-segregation and association analyses show that p.Arg1933* can act as a Mendelian mutation in trans with the Alu insertion, but might also associate with disease in combination with two alleles in the EYS gene in a non-Mendelian pattern of heredity. Our results suggest that rare conditions such as HRDs can be paradoxically determined by relatively common variants, following a quasi-Mendelian model linking monogenic and complex inheritance.
Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos
Authors: Wu Yi , Zhang Jing , Peng Boya , Tian Dan , Zhang Dong , Li Yang , Feng Xiaoyu , Liu Jinghao , Li Jun , Zhang Teng , Liu Xiaoyong , Lu Jing , Chen Baian , Wang Songlin 
Published: June 2019

AbstractA substantial number of mouse genes, about 25%, are embryonically lethal when knocked out. Using current genetic tools, such as the CRISPR-Cas9 system, it is difficult—or even impossible—to produce viable mice with heritable embryonically lethal mutations. Here, we establish a one-step method for microinjection of CRISPR reagents into one blastomere of two-cell embryos to generate viable chimeric founder mice with a heritable embryonically lethal mutation, of either Virma or Dpm1. By examining founder mice, we identify a phenotype and role of Virma in regulating kidney metabolism in adult mice. Additionally, we generate knockout mice with a heritable postnatally lethal mutation, of either Slc17a5 or Ctla-4, and study its function in vivo. This one-step method provides a convenient system that rapidly generates knockout mice possessing lethal phenotypes. This allows relatively easy in vivo study of the associated genes’ functions.
Actomyosin-driven force patterning controls endocytosis at the immune synapse
Authors: Kumari Anita , Pineau Judith , Sáez Pablo J. , Maurin Mathieu , Lankar Danielle , San Roman Mabel , Hennig Katharina , Boura Vanessa F. , Voituriez Raphael , Karlsson Mikael C. I. , Balland Martial , Lennon Dumenil Ana-Maria , Pierobon Paolo 
Published: June 2019

AbstractAn important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules and information. Although mechanics has been shown to play an important role in this process, how forces organize and impact on synapse function is unknown. We find that mechanical forces are spatio-temporally patterned at the immune synapse: global pulsatile myosin II-driven tangential forces are observed at the synapse periphery while localised forces generated by invadosome-like F-actin protrusions are detected at its centre. Noticeably, we observe that these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis and require myosin II contractility to form. The interplay between global and local forces dictated by the organization of the actomyosin cytoskeleton therefore controls endocytosis at the immune synapse.
European mushroom assemblages are darker in cold climates
Authors: Krah Franz-Sebastian , Büntgen Ulf , Schaefer Hanno , Müller Jörg , Andrew Carrie , Boddy Lynne , Diez Jeffrey , Egli Simon , Freckleton Robert , Gange Alan C. , Halvorsen Rune , Heegaard Einar , Heideroth Antje , Heibl Christoph , Heilmann-Clausen Jacob , Høiland Klaus , Kar Ritwika , Kauserud Håvard , Kirk Paul M. , Kuyper Thomas W. , Krisai-Greilhuber Irmgard , Norden Jenni , Papastefanou Phillip , Senn-Irlet Beatrice , Bässler Claus 
Published: June 2019

AbstractThermal melanism theory states that dark-colored ectotherm organisms are at an advantage at low temperature due to increased warming. This theory is generally supported for ectotherm animals, however, the function of colors in the fungal kingdom is largely unknown. Here, we test whether the color lightness of mushroom assemblages is related to climate using a dataset of 3.2 million observations of 3,054 species across Europe. Consistent with the thermal melanism theory, mushroom assemblages are significantly darker in areas with cold climates. We further show differences in color phenotype between fungal lifestyles and a lifestyle differentiated response to seasonality. These results indicate a more complex ecological role of mushroom colors and suggest functions beyond thermal adaption. Because fungi play a crucial role in terrestrial carbon and nutrient cycles, understanding the links between the thermal environment, functional coloration and species’ geographical distributions will be critical in predicting ecosystem responses to global warming.
Global impacts of future cropland expansion and intensification on agricultural markets and biodiversity
Authors: Zabel Florian , Delzeit Ruth , Schneider Julia M. , Seppelt Ralf , Mauser Wolfram , Václavík Tomáš 
Published: June 2019

AbstractWith rising demand for biomass, cropland expansion and intensification represent the main strategies to boost agricultural production, but are also major drivers of biodiversity decline. We investigate the consequences of attaining equal global production gains by 2030, either by cropland expansion or intensification, and analyse their impacts on agricultural markets and biodiversity. We find that both scenarios lead to lower crop prices across the world, even in regions where production decreases. Cropland expansion mostly affects biodiversity hotspots in Central and South America, while cropland intensification threatens biodiversity especially in Sub-Saharan Africa, India and China. Our results suggest that production gains will occur at the costs of biodiversity predominantly in developing tropical regions, while Europe and North America benefit from lower world market prices without putting their own biodiversity at risk. By identifying hotspots of potential future conflicts, we demonstrate where conservation prioritization is needed to balance agricultural production with conservation goals.
NLRC5 inhibits neointima formation following vascular injury and directly interacts with PPARγ
Authors: Luan Peipei , Jian Weixia , Xu Xu , Kou Wenxin , Yu Qing , Hu Handan , Li Dali , Wang Wei , Feinberg Mark W. , Zhuang Jianhui , Xu Yawei , Peng Wenhui 
Published: June 2019

AbstractNLR Family CARD Domain Containing 5 (NLRC5), an important immune regulator in innate immunity, is involved in regulating inflammation and antigen presentation. However, the role of NLRC5 in vascular remodeling remains unknown. Here we report the role of NLRC5 on vascular remodeling and provide a better understanding of its underlying mechanism. Nlrc5 knockout (Nlrc5−/−) mice exhibit more severe intimal hyperplasia compared with wild-type mice after carotid ligation. Ex vivo data shows that NLRC5 deficiency leads to increased proliferation and migration of human aortic smooth muscle cells (HASMCs). NLRC5 binds to PPARγ and inhibits HASMC dedifferentiation. NACHT domain of NLRC5 is essential for the interaction with PPARγ and stimulation of PPARγ activity. Pioglitazone significantly rescues excessive intimal hyperplasia in Nlrc5−/− mice and attenuates the increased proliferation and dedifferentiation in NLRC5-deficient HASMCs. Our study demonstrates that NLRC5 regulates vascular remodeling by directly inhibiting SMC dysfunction via its interaction with PPARγ.
SETD1A protects from senescence through regulation of the mitotic gene expression program
Authors: Tajima Ken , Matsuda Satoru , Yae Toshifumi , Drapkin Benjamin J. , Morris Robert , Boukhali Myriam , Niederhoffer Kira , Comaills Valentine , Dubash Taronish , Nieman Linda , Guo Hongshan , Magnus Neelima K. C. , Dyson Nick , Shioda Toshihiro , Haas Wilhelm , Haber Daniel A. , Maheswaran Shyamala 
Published: June 2019

AbstractSETD1A, a Set1/COMPASS family member maintaining histone-H3-lysine-4 (H3K4) methylation on transcriptionally active promoters, is overexpressed in breast cancer. Here, we show that SETD1A supports mitotic processes and consequentially, its knockdown induces senescence. SETD1A, through promoter H3K4 methylation, regulates several genes orchestrating mitosis and DNA-damage responses, and its depletion causes chromosome misalignment and segregation defects. Cell cycle arrest in SETD1A knockdown senescent cells is independent of mutations in p53, RB and p16, known senescence mediators; instead, it is sustained through transcriptional suppression of SKP2, which degrades p27 and p21. Rare cells escaping senescence by restoring SKP2 expression display genomic instability. In > 200 cancer cell lines and in primary circulating tumor cells, SETD1A expression correlates with genes promoting mitosis and cell cycle suggesting a broad role in suppressing senescence induced by aberrant mitosis. Thus, SETD1A is essential to maintain mitosis and proliferation and its suppression unleashes the tumor suppressive effects of senescence.
WDFY2 restrains matrix metalloproteinase secretion and cell invasion by controlling VAMP3-dependent recycling
Authors: Sneeggen Marte , Pedersen Nina Marie , Campsteijn Coen , Haugsten Ellen Margrethe , Stenmark Harald , Schink Kay Oliver 
Published: June 2019

AbstractCancer cells secrete matrix metalloproteinases to remodel the extracellular matrix, which enables them to overcome tissue barriers and form metastases. The membrane-bound matrix metalloproteinase MT1-MMP (MMP14) is internalized by endocytosis and recycled in endosomal compartments. It is largely unknown how endosomal sorting and recycling of MT1-MMP are controlled. Here, we show that the endosomal protein WDFY2 controls the recycling of MT1-MMP. WDFY2 localizes to endosomal tubules by binding to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns3P). We identify the v-SNARE VAMP3 as an interaction partner of WDFY2. WDFY2 knockout causes a strong redistribution of VAMP3 into small vesicles near the plasma membrane. This is accompanied by increased, VAMP3-dependent secretion of MT1-MMP, enhanced degradation of extracellular matrix, and increased cell invasion. WDFY2 is frequently lost in metastatic cancers, most predominantly in ovarian and prostate cancer. We propose that WDFY2 acts as a tumor suppressor by serving as a gatekeeper for VAMP3 recycling.
MFS transporter from Botrytis cinerea provides tolerance to glucosinolate-breakdown products and is required for pathogenicity
Authors: Vela-Corcía David , Aditya Srivastava Dhruv , Dafa-Berger Avis , Rotem Neta , Barda Omer , Levy Maggie 
Published: June 2019

AbstractGlucosinolates accumulate mainly in cruciferous plants and their hydrolysis-derived products play important roles in plant resistance against pathogens. The pathogen Botrytis cinerea has variable sensitivity to glucosinolates, but the mechanisms by which it responds to them are mostly unknown. Exposure of B. cinerea to glucosinolate-breakdown products induces expression of the Major Facilitator Superfamily transporter, mfsG, which functions in fungitoxic compound efflux. Inoculation of B. cinerea on wild-type Arabidopsis thaliana plants induces mfsG expression to higher levels than on glucosinolate-deficient A. thaliana mutants. A B. cinerea strain lacking functional mfsG transporter is deficient in efflux ability. It accumulates more isothiocyanates (ITCs) and is therefore more sensitive to this compound in vitro; it is also less virulent to glucosinolates-containing plants. Moreover, mfsG mediates ITC efflux in Saccharomyces cerevisiae cells, thereby conferring tolerance to ITCs in the yeast. These findings suggest that mfsG transporter is a virulence factor that increases tolerance to glucosinolates.
The influence of geostrophic strain on oceanic ageostrophic motion and surface chlorophyll
Authors: Zhang Zhengguang , Qiu Bo , Klein Patrice , Travis Seth 
Published: June 2019

AbstractOceanic submesoscale ageostrophic processes have been progressively recognized as an important upwelling mechanism to close the nutrient budget and sustain the observed primary production of phytoplankton in the euphotic layer. Their relatively small spatio-temporal scales (of 1~10 km and a few days) have hindered a systematic observational quantification of the submesoscale ageostrophic flow variability and its impact on ocean biogeochemistry. By combining surface drifters, satellite altimetry and satellite ocean-color data, we detect that when the strain rate of mesoscale surface geostrophic flow is strong, it favors a higher ageostrophic kinetic energy level and an increase in surface chlorophyll concentration. The strain-induced frontal processes are characterized by a surface chlorophyll increase and secondary ageostrophic upwelling along the light side of the oceanic density front. Further analysis indicates that the balanced ageostrophic motions with longer time scales are more effective in inducing chlorophyll increase than the unbalanced shorter time-scale wave motions.
Doping strain induced bi-Ti3+ pairs for efficient N2 activation and electrocatalytic fixation
Authors: Cao Na , Chen Zheng , Zang Ketao , Xu Jie , Zhong Jun , Luo Jun , Xu Xin , Zheng Gengfeng 
Published: June 2019

AbstractThe electrochemical N2 fixation to produce ammonia is attractive but significantly challenging with low yield and poor selectivity. Herein, we first used density function theory calculations to reveal adjacent bi-Ti3+ pairs formed on anatase TiO2 as the most active electrocatalytic centers for efficient N2 lying-down chemisorption and activation. Then, by doping of anatase TiO2 with Zr4+ that has similar d-electron configuration and oxide structure but relatively larger ionic size, the adjacent bi-Ti3+ sites were induced and enriched via a strained effect, which in turn enhanced the formation of oxygen vacancies. The Zr4+-doped anatase TiO2 exhibited excellent electrocatalytic N2 fixation performances, with an ammonia production rate (8.90 µg·h−1·cm−2) and a Faradaic efficiency of 17.3% at −0.45 V versus reversible hydrogen electrode under ambient aqueous conditions. Moreover, our work suggests a viewpoint to understand and apply the same-valance dopants in heterogeneous catalysis, which is generally useful but still poorly understood.
Tethering of vesicles to the Golgi by GMAP210 controls LAT delivery to the immune synapse
Authors: Zucchetti Andres Ernesto , Bataille Laurence , Carpier Jean-Marie , Dogniaux Stéphanie , San Roman-Jouve Mabel , Maurin Mathieu , Stuck Michael W. , Rios Rosa M. , Baldari Cosima T. , Pazour Gregory J. , Hivroz Claire 
Published: June 2019

AbstractThe T cell immune synapse is a site of intense vesicular trafficking. Here we show that the golgin GMAP210, known to capture vesicles and organize membrane traffic at the Golgi, is involved in the vesicular transport of LAT to the immune synapse. Upon activation, more GMAP210 interact with LAT-containing vesicles and go together with LAT to the immune synapse. Regulating LAT recruitment and LAT-dependent signaling, GMAP210 controls T cell activation. Using a rerouting and capture assay, we show that GMAP210 captures VAMP7-decorated vesicles. Overexpressing different domains of GMAP210, we also show that GMAP210 allows their specific delivery to the immune synapse by tethering LAT-vesicles to the Golgi. Finally, in a model of ectopic expression of LAT in ciliated cells, we show that GMAP210 tethering activity controls the delivery of LAT to the cilium. Hence, our results reveal a function for the golgin GMAP210 conveying specific vesicles to the immune synapse.
Structure of the substrate-engaged SecA-SecY protein translocation machine
Authors: Ma Chengying , Wu Xiaofei , Sun Dongjie , Park Eunyong , Catipovic Marco A. , Rapoport Tom A. , Gao Ning , Li Long 
Published: June 2019

AbstractThe Sec61/SecY channel allows the translocation of many proteins across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane. In bacteria, most secretory proteins are transported post-translationally through the SecY channel by the SecA ATPase. How a polypeptide is moved through the SecA-SecY complex is poorly understood, as structural information is lacking. Here, we report an electron cryo-microscopy (cryo-EM) structure of a translocating SecA-SecY complex in a lipid environment. The translocating polypeptide chain can be traced through both SecA and SecY. In the captured transition state of ATP hydrolysis, SecA’s two-helix finger is close to the polypeptide, while SecA’s clamp interacts with the polypeptide in a sequence-independent manner by inducing a short β-strand. Taking into account previous biochemical and biophysical data, our structure is consistent with a model in which the two-helix finger and clamp cooperate during the ATPase cycle to move a polypeptide through the channel.
PLK1 facilitates chromosome biorientation by suppressing centromere disintegration driven by BLM-mediated unwinding and spindle pulling
Authors: Addis Jones Owen , Tiwari Ankana , Olukoga Tomisin , Herbert Alex , Chan Kok-Lung 
Published: June 2019

AbstractCentromeres provide a pivotal function for faithful chromosome segregation. They serve as a foundation for the assembly of the kinetochore complex and spindle connection, which is essential for chromosome biorientation. Cells lacking Polo-like kinase 1 (PLK1) activity suffer severe chromosome alignment defects, which is believed primarily due to unstable kinetochore-microtubule attachment. Here, we reveal a previously undescribed mechanism named ‘centromere disintegration’ that drives chromosome misalignment in PLK1-inactivated cells. We find that PLK1 inhibition does not necessarily compromise metaphase establishment, but instead its maintenance. We demonstrate that this is caused by unlawful unwinding of DNA by BLM helicase at a specific centromere domain underneath kinetochores. Under bipolar spindle pulling, the distorted centromeres are promptly decompacted into DNA threadlike molecules, leading to centromere rupture and whole-chromosome arm splitting. Consequently, chromosome alignment collapses. Our study unveils an unexpected role of PLK1 as a chromosome guardian to maintain centromere integrity for chromosome biorientation.
Co-emergence of magnetic order and structural fluctuations in magnetite
Authors: Perversi Giuditta , Pachoud Elise , Cumby James , Hudspeth Jessica M. , Wright Jon P. , Kimber Simon A. J. , Paul Attfield J. 
Published: June 2019

AbstractThe nature of the Verwey transition occurring at TV ≈ 125 K in magnetite (Fe3O4) has been an outstanding problem over many decades. A complex low temperature electronic order was recently discovered and associated structural fluctuations persisting above TV are widely reported, but the origin of the underlying correlations and hence of the Verwey transition remains unclear. Here we show that local structural fluctuations in magnetite emerge below the Curie transition at TC ≈ 850 K, through X-ray pair distribution function analysis. Around 80% of the low temperature correlations emerge in proportion to magnetization below TC. This confirms that fluctuations in Fe-Fe bonding arising from magnetic order are the primary electronic instability and hence the origin of the Verwey transition. Such hidden instabilities may be important to other spin-polarised conductors and orbitally degenerate materials.
Identifying peripersonal space boundaries in newborns
Authors: Orioli Giulia , Santoni Alessandro , Dragovic Danica , Farroni Teresa 
Published: June 2019

AbstractPeripersonal space immediately surrounds the body and can be represented in the brain as a multisensory and sensorimotor interface mediating physical and social interactions between body and environment. Very little consideration has been given to the ontogeny of peripersonal spatial representations in early postnatal life, despite the crucial roles of peripersonal space and its adaptive relevance as the space where infants’ earliest interactions take place. Here, we investigated whether peripersonal space could be considered a delimited portion of space with defined boundaries soon after birth. Our findings showed for the first time that newborns’ saccadic reaction times to a tactile stimulus simultaneous to sounds with different intensities changed based on the sound intensity. In particular, they were significantly faster when the sound was lounder than a critical intensity, in a pattern that closely resembled that showed by adults. Therefore, provided that sound intensity on its own can cue newborns’ sound distance perception, we speculate that this critical distance could be considered the boundary of newborns’ rudimentary peripersonal space. Altogether, our findings suggest that soon after birth peripersonal space may be already considered as a bounded portion of space, perhaps instrumental to drive newborns’ attention towards events and people within it.
Building a DNA barcode library for the freshwater fishes of Bangladesh
Authors: Rahman Md. Mizanur , Norén Michael , Mollah Abdur Rob , Kullander Sven O. 
Published: June 2019

AbstractWe sequenced the standard DNA barcode gene fragment in 694 newly collected specimens, representing 243 species level Operational Barcode Units (OBUs) of freshwater fishes from Bangladesh. We produced coi sequences for 149 out of the 237 species already recorded from Bangladesh. Another 83 species sequenced were not previously recorded for the country, and include about 30 undescribed or potentially undescribed species. Several of the taxa that we could not sample represent erroneous records for the country, or sporadic occurrences. Species identifications were classified at confidence levels 1(best) to 3 (worst). We propose the new term Operational Barcode Unit (OBU) to simplify references to would-be DNA barcode sequences and sequence clusters. We found one case where there were two mitochondrial lineages present in the same species, several cases of cryptic species, one case of introgression, one species yielding a pseudogene to standard barcoding primers, and several cases of taxonomic uncertainty and need for taxonomic revision. Large scale national level DNA barcode prospecting in high diversity regions may suffer from lack of taxonomic expertise that cripples the result. Consequently, DNA barcoding should be performed in the context of taxonomic revision, and have a defined, competent end-user.