bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production
Authors: Sousa Jeremy , Cá Baltazar , Maceiras Ana Raquel , Simões-Costa Luisa , Fonseca Kaori L. , Fernandes Ana Isabel , Ramos Angélica , Carvalho Teresa , Barros Leandro , Magalhães Carlos , Chiner-Oms Álvaro , Machado Henrique , Veiga Maria Isabel , Singh Albel , Pereira Rui , Amorim António , Vieira Jorge , Vieira Cristina P. , Bhatt Apoorva , Rodrigues Fernando , Rodrigues Pedro N. S. , Gagneux Sebastien , Castro António Gil , Guimarães João Tiago , Bastos Helder Novais , Osório Nuno S. , Comas Iñaki , Saraiva Margarida 
Published: April 2020

AbstractGenetic diversity ofMycobacterium tuberculosisaffects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show thatM.tuberculosisisolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple donors. By contrast, bacteria from patients with severe TB do not do so. Secretion of IL-1β is a good surrogate of the differences observed, and thus to classify strains as probable drivers of different TB severities. Furthermore, we demonstrate thatM.tuberculosisisolates that induce low levels of IL-1β production can evade macrophage cytosolic surveillance systems, including cGAS and the inflammasome. Isolates exhibiting this evasion strategy carry candidate mutations, generating sigA recognition boxes or affecting components of the ESX-1 secretion system. Therefore, we provide evidence thatM.tuberculosisstrains manipulate host-pathogen interactions to drive variable TB severities.
Novel metabolic role for BDNF in pancreatic β-cell insulin secretion
Authors: Fulgenzi Gianluca , Hong Zhenyi , Tomassoni-Ardori Francesco , Barella Luiz F. , Becker Jodi , Barrick Colleen , Swing Deborah , Yanpallewar Sudhirkumar , Croix Brad St , Wess Jürgen , Gavrilova Oksana , Tessarollo Lino 
Published: April 2020

AbstractBDNF signaling in hypothalamic circuitries regulates mammalian food intake. However, whether BDNF exerts metabolic effects on peripheral organs is currently unknown. Here, we show that the BDNF receptor TrkB.T1 is expressed by pancreatic β-cells where it regulates insulin release. Mice lacking TrkB.T1 show impaired glucose tolerance and insulin secretion. β-cell BDNF-TrkB.T1 signaling triggers calcium release from intracellular stores, increasing glucose-induced insulin secretion. Additionally, BDNF is secreted by skeletal muscle and muscle-specific BDNF knockout phenocopies the β-cell TrkB.T1 deletion metabolic impairments. The finding that BDNF is also secreted by differentiated human muscle cells and induces insulin secretion in human islets via TrkB.T1 identifies a new regulatory function of BDNF on metabolism that is independent of CNS activity. Our data suggest that muscle-derived BDNF may be a key factor mediating increased glucose metabolism in response to exercise, with implications for the treatment of diabetes and related metabolic diseases.
LGR5 marks targetable tumor-initiating cells in mouse liver cancer
Authors: Cao Wanlu , Li Meng , Liu Jiaye , Zhang Shaoshi , Noordam Lisanne , Verstegen Monique M. A. , Wang Ling , Ma Buyun , Li Shan , Wang Wenshi , Bolkestein Michiel , Doukas Michael , Chen Kan , Ma Zhongren , Bruno Marco , Sprengers Dave , Kwekkeboom Jaap , van der Laan Luc J. W. , Smits Ron , Peppelenbosch Maikel P. , Pan Qiuwei 
Published: April 2020

AbstractCancer stem cells (CSCs) or tumor-initiating cells (TICs) are thought to be the main drivers for disease progression and treatment resistance across various cancer types. Identifying and targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the enrichment of LGR5 expressing cells, a well-recognized stem cell marker, in mouse liver tumors, and the upregulation of LGR5 expression in human hepatocellular carcinoma. Isolated LGR5 expressing cells from mouse liver tumors are superior in initiating organoids and forming tumors upon engraftment, featuring candidate TICs. These cells are resistant to conventional treatment including sorafenib and 5-FU. Importantly, LGR5 lineage ablation significantly inhibits organoid initiation and tumor growth. The combination of LGR5 ablation with 5-FU, but not sorafenib, further augments the therapeutic efficacy in vivo. Thus, we have identified the LGR5+ compartment as an important TIC population, representing a viable therapeutic target for combating liver cancer.
Arabidopsis FHY3 and FAR1 integrate light and strigolactone signaling to regulate branching
Authors: Xie Yurong , Liu Yang , Ma Mengdi , Zhou Qin , Zhao Yongping , Zhao Binbin , Wang Baobao , Wei Hongbin , Wang Haiyang 
Published: April 2020

AbstractBranching/tillering is an important parameter of plant architecture and is tightly regulated by both internal factors (such as plant hormones) and external factors (such as light conditions). How the various signaling pathways converge to coordinately regulate branching is not well understood. Here, we report that in Arabidopsis, FHY3 and FAR1, two homologous transcription factors essential for phytochrome A-mediated light signaling, and SMXL6/SMXL7/SMXL8, three key repressors of the strigolactone (SL) signaling pathway, directly interact with SPL9 and SPL15 and suppress their transcriptional activation of BRC1, a key repressor of branching, thus promoting branching. In addition, FHY3 and FAR1 also directly up-regulate the expression of SMXL6 and SMXL7 to promote branching. Simulated shade treatment reduces the accumulation of FHY3 protein, leading to increased expression of BRC1 and reduced branching. Our results establish an integrated model of light and SL coordinately regulating BRC1 expression and branching through converging at the BRC1 promoter.
First fossil frog from Antarctica: implications for Eocene high latitude climate conditions and Gondwanan cosmopolitanism of Australobatrachia
Authors: Mörs Thomas , Reguero Marcelo , Vasilyan Davit 
Published: April 2020

AbstractCenozoic ectothermic continental tetrapods (amphibians and reptiles) have not been documented previously from Antarctica, in contrast to all other continents. Here we report a fossil ilium and an ornamented skull bone that can be attributed to the Recent, South American, anuran family Calyptocephalellidae or helmeted frogs, representing the first modern amphibian found in Antarctica. The two bone fragments were recovered in Eocene, approximately 40 million years old, sediments on Seymour Island, Antarctic Peninsula. The record of hyperossified calyptocephalellid frogs outside South America supports Gondwanan cosmopolitanism of the anuran clade Australobatrachia. Our results demonstrate that Eocene freshwater ecosystems in Antarctica provided habitats favourable for ectothermic vertebrates (with mean annual precipitation ≥900 mm, coldest month mean temperature ≥3.75 °C, and warmest month mean temperature ≥13.79 °C), at a time when there were at least ephemeral ice sheets existing on the highlands within the interior of the continent.
Potential Pathogenic Bacteria in Seminal Microbiota of Patients with Different Types of Dysspermatism
Authors: Yang Huijun , Zhang Jiaming , Xue Zhiwei , Zhao Changying , Lei Lijun , Wen Yan , Dong Yunling , Yang Junjie , Zhang Lei 
Published: April 2020

AbstractHuman microbiota play an important role in the health of their human hosts. Recent studies have demonstrated that microbiota exist in seminal plasma. The current study aims to elucidate whether seminal microbiota exist in patients with different types of dysspermatism and whether bacterial biomarkers can be identified for them. A total of 159 study participants were recruited, including 22 patients with oligoasthenospermia, 58 patients with asthenospermia, 8 patients with azoospermia, 13 patients with oligospermia, and 58 matched healthy controls. Seminal microbiota composition was analyzed using 16S rRNA gene-based sequencing. The results showed that the composition of seminal microbiota of patients with dysspermatism differed from those of healthy controls. Comparison of the microbiota composition in semen samples from patients with different types of dysspermatism showed that microbiota in patients with asthenospermia and oligoasthenospermia were distinct from healthy controls in beta diversity (P < 0.05). Characteristic biomarkers, including Ureaplasma, Bacteroides, Anaerococcus, Finegoldia, Lactobacillus and Acinetobacter lwoffii, were identified based on LEfSe analysis. Inferred functional analysis based on seminal microbiome data further indicated the presence of potential pathogenic biomarkers in patients with asthenospermia and oligoasthenospermia. These results provided profiles of seminal microbiota exhibited in different types of dysspermatism, thus providing new insights into their pathogenesis.
Differential Effects of the Hormonal and Copper Intrauterine Device on the Endometrial Transcriptome
Authors: Smith-McCune Karen , Thomas Reuben , Averbach Sarah , Seidman Dominika , Takeda Margaret , Houshdaran Sahar , Giudice Linda C. 
Published: April 2020

AbstractThe contraceptive effectiveness of intrauterine devices (IUDs) has been attributed in part to a foreign body reaction in the endometrium. We performed this study to better understand mechanisms of action of contraceptives of by studying their effects on endometrial and cervical transcriptomes. We collected endometrial and cervical biopsies from women using the levonorgestrel-releasing intrauterine system (LNG-IUS, n = 11), copper intrauterine device (cu-IUD, n = 13) or levonorgestrel-containing combined oral contraceptives (COC, n = 12), and from women not using contraceptives (control group, n = 11). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. In endometrial samples from cu-IUD users, there were no genes with statistically significant differential expression compared to controls. In LNG-IUS users, 2509 genes were differentially expressed and mapped predominantly onto immune and inflammatory pathways. The cervical samples showed no statistically significant differential gene expression compared to controls. Hormonal and copper IUDs have significantly different effects on the endometrial transcriptome, with the LNG-IUS transcriptome showing pronounced inflammation and immune activation compared to controls whereas the cu-IUD transcriptome was indistinguishable from luteal phase endometrium. These findings argue against a foreign body reaction as a common mechanism of action of IUDs.
Bat coronavirus phylogeography in the Western Indian Ocean
Authors: Joffrin Léa , Goodman Steven M. , Wilkinson David A. , Ramasindrazana Beza , Lagadec Erwan , Gomard Yann , Le Minter Gildas , Dos Santos Andréa , Corrie Schoeman M. , Sookhareea Rajendraprasad , Tortosa Pablo , Julienne Simon , Gudo Eduardo S. , Mavingui Patrick , Lebarbenchon Camille 
Published: April 2020

AbstractBats provide key ecosystem services such as crop pest regulation, pollination, seed dispersal, and soil fertilization. Bats are also major hosts for biological agents responsible for zoonoses, such as coronaviruses (CoVs). The islands of the Western Indian Ocean are identified as a major biodiversity hotspot, with more than 50 bat species. In this study, we tested 1,013 bats belonging to 36 species from Mozambique, Madagascar, Mauritius, Mayotte, Reunion Island and Seychelles, based on molecular screening and partial sequencing of the RNA-dependent RNA polymerase gene. In total, 88 bats (8.7%) tested positive for coronaviruses, with higher prevalence in Mozambican bats (20.5% ± 4.9%) as compared to those sampled on islands (4.5% ± 1.5%). Phylogenetic analyses revealed a large diversity of α- and β-CoVs and a strong signal of co-evolution between CoVs and their bat host species, with limited evidence for host-switching, except for bat species sharing day roost sites. These results highlight that strong variation between islands does exist and is associated with the composition of the bat species community on each island. Future studies should investigate whether CoVs detected in these bats have a potential for spillover in other hosts.
Influence of cluster thinning and girdling on aroma composition in ‘Jumeigui’ table grape
Authors: Xi Xiaojun , Zha Qian , He Yani , Tian Yihua , Jiang Aili 
Published: April 2020

AbstractCluster thinning and girdling are common and simple practices applied to improve berry quality in table grape cultivation. However, there is limited information about the accumulation and biosynthesis of the entire aromatic profile under cluster thinning and girdling, notably in table grapes. This research investigated the influences of cluster thinning and girdling (alone or in combination) on aroma profiles, particularly the changes in biosynthesis and accumulation of Muscat-flavored related compounds from véraison to harvest in ‘Jumeigui’ grape. Cluster thinning and girdling (alone or in combination) significantly increased the concentrations of total soluble solids (TSS) and key aromatic compounds at harvest, with higher concentrations of both under cluster thinning than girdling. Berry weight and titratable acidity (TA) were unaffected by cluster thinning, girdling, or in combination at harvest. Linalool, the most abundant and active odorant related to Muscat flavor, accumulated in 28.6% and 20.2% higher concentrations from cluster thinning than control and girdling at maturity, respectively. Furthermore, higherDXS3transcript abundance in cluster thinning groups might contribute to the increased accumulation of terpenes and linalool in ‘Jumeigui’ grape. The results will contribute to further understand the mechanism of source/sink ratio modulation on aroma accumulation and better apply cluster thinning and girdling for grape production.
A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models
Authors: Ganz Javier , Shacham Talya , Kramer Maria , Shenkman Marina , Eiger Hagit , Weinberg Nitai , Iancovici Ori , Roy Somnath , Simhaev Luba , Da’adoosh Benny , Engel Hamutal , Perets Nisim , Barhum Yael , Portnoy Moshe , Offen Daniel , Lederkremer Gerardo Z. 
Published: April 2020

AbstractOne of the pathways of the unfolded protein response, initiated by PKR-like endoplasmic reticulum kinase (PERK), is key to neuronal homeostasis in neurodegenerative diseases. PERK pathway activation is usually accomplished by inhibiting eIF2α-P dephosphorylation, after its phosphorylation by PERK. Less tried is an approach involving direct PERK activation without compromising long-term recovery of eIF2α function by dephosphorylation. Here we show major improvement in cellular (STHdhQ111/111) and mouse (R6/2) Huntington's disease (HD) models using a potent small molecule PERK activator that we developed, MK-28. MK-28 showed PERK selectivity in vitro on a 391-kinase panel and rescued cells (but not PERK−/− cells) from ER stress-induced apoptosis. Cells were also rescued by the commercial PERK activator CCT020312 but MK-28 was significantly more potent. Computational docking suggested MK-28 interaction with the PERK activation loop. MK-28 exhibited remarkable pharmacokinetic properties and high BBB penetration in mice. Transient subcutaneous delivery of MK-28 significantly improved motor and executive functions and delayed death onset in R6/2 mice, showing no toxicity. Therefore, PERK activation can treat a most aggressive HD model, suggesting a possible approach for HD therapy and worth exploring for other neurodegenerative disorders.
From graphene oxide towards aminated graphene: facile synthesis, its structure and electronic properties
Authors: Rabchinskii Maxim K. , Ryzhkov Sergei A. , Kirilenko Demid A. , Ulin Nikolay V. , Baidakova Marina V. , Shnitov Vladimir V. , Pavlov Sergei I. , Chumakov Ratibor G. , Stolyarova Dina Yu. , Besedina Nadezhda A. , Shvidchenko Aleksandr V. , Potorochin Dmitrii V. , Roth Friedrich , Smirnov Dmitry A. , Gudkov Maksim V. , Brzhezinskaya Maria , Lebedev Oleg I. , Melnikov Valery P. , Brunkov Pavel N. 
Published: April 2020

AbstractIn this paper we present a facile method for the synthesis of aminated graphene derivative through simultaneous reduction and amination of graphene oxide via two-step liquid phase treatment with hydrobromic acid and ammonia solution in mild conditions. The amination degree of the obtained aminated reduced graphene oxide is of about 4 at.%, whereas C/O ratio is up to 8.8 as determined by means of X-ray photoelectron spectroscopy. The chemical reactivity of the introduced amine groups is further verified by successful test covalent bonding of the obtained aminated graphene with 3-Chlorobenzoyl chloride. The morphological features and electronic properties, namely conductivity, valence band structure and work function are studied as well, illustrating the influence of amine groups on graphene structure and physical properties. Particularly, the increase of the electrical conductivity, reduction of the work function value and tendency to form wrinkled and corrugated graphene layers are observed in the aminated graphene derivative compared to the pristine reduced graphene oxide. As obtained aminated graphene could be used for photovoltaic, biosensing and catalysis application as well as a starting material for further chemical modifications.
Exogenous melatonin improves glutathione content, redox state and increases essential oil production in two Salvia species under drought stress
Authors: Bidabadi Siamak Shirani , VanderWeide Joshua , Sabbatini Paolo 
Published: April 2020

AbstractThis research was conducted to understand the influence of foliar applied melatonin (0, 50, 100, 150 and 200 μM) on two Salvia species (Salvia nemorosa L., and Salvia reuterana Boiss) under conditions of water stress. Water stress was applied using a reduced irrigation strategy based on re-watering at 80%, 60% and 40% of the field capacity (FC). Increasing water stress, while significantly enhancing malondialdehyde (MDA), H2O2, electrolyte leakage, oxidized glutathione (GSSG), and total glutathione (GT), reduced glutathione (GSH), catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and glutathione reductase (GR) activities, which led to a marked reduction in fluorescence (Fv/Fm). Foliar application of melatonin alleviated the oxidative stress by increasing GT, CAT, POD, SOD and GR activities and reducing GSSG. In particular, melatonin heightened GSH content as well as the ratio of GSH/GSSG when compared to non-sprayed water stressed plants. Melatonin-treated plants had significantly lower SOD and POD activities than control plants under drought stress, while the CAT activity was enhanced with the foliar treatment. Essential oil yield of both Salvia species increased with the decrease in irrigation from 80% to 60% FC but diminished with the more severe water deficit (40% FC). Essential oil components of Salvia nemorosa were β- caryophyllene, germacrene- B, spathulenol, and cis- β- farnesene, while (E) - β- ocimene, α- gurjnnene, germacrene-D, hexyl acetate and aromadendrene was the major constituents of Salvia reuterana. When plants were subjected to water deficit, melatonin treatment increased the concentration and composition of the essential oil. In particular, melatonin treatments improved the primary oil components in both species when compared to non-melatonin treated plants. In conclusion, reduced irrigation regimes as well as melatonin treatments resulted in a significant improvement of essential oil production and composition in both Salvia species.
Uptake of osteoblast-derived extracellular vesicles promotes the differentiation of osteoclasts in the zebrafish scale
Authors: Kobayashi-Sun Jingjing , Yamamori Shiori , Kondo Mao , Kuroda Junpei , Ikegame Mika , Suzuki Nobuo , Kitamura Kei-ichiro , Hattori Atsuhiko , Yamaguchi Masaaki , Kobayashi Isao 
Published: April 2020

AbstractDifferentiation of osteoclasts (OCs) from hematopoietic cells requires cellular interaction with osteoblasts (OBs). Due to the difficulty of live-imaging in the bone, however, the cellular and molecular mechanisms underlying intercellular communication involved in OC differentiation are still elusive. Here, we develop a fracture healing model using the scale of trap:GFP; osterix:mCherry transgenic zebrafish to visualize the interaction between OCs and OBs. Transplantation assays followed by flow cytometric analysis reveal that most trap:GFPhigh OCs in the fractured scale are detected in the osterix:mCherry+ fraction because of uptake of OB-derived extracellular vesicles (EVs). In vivo live-imaging shows that immature OCs actively interact with osterix:mCherry+ OBs and engulf EVs prior to convergence at the fracture site. In vitro cell culture assays show that OB-derived EVs promote OC differentiation via Rankl signaling. Collectively, these data suggest that EV-mediated intercellular communication with OBs plays an important role in the differentiation of OCs in bone tissue.
Die Erlanger Universitätspsychiatrie im Nationalsozialismus.
Authors: Braun Birgit 
Published: April 2020

ZUSAMMENFASSUNG
Hintergrund Das 200-jährige Jubiläum der Universitätspsychiatrie Erlangen motiviert zu einer kritisch-historischen Analyse der Rolle Friedrich Meggendorfers (1880–1953) als Psychiater im Nationalsozialismus.
Methode Eine jetzige Auswertung bislang unberücksichtigter Quellen ermöglichte es, die Rolle Friedrich Meggendorfers als NS-Hochschulpsychiater differenziert einzuordnen.
Ergebnis Meggendorfers Expertentum in Erbpsychiatrie und forensischer Eugenik könnte der ausschlaggebende Grund gewesen sein für seine Berufung als Ordinarius für Psychiatrie nach Erlangen im Jahr 1934. Am 19.11.1945 wurde Meggendorfer von der Militärregierung seines Amtes enthoben. Obwohl Meggendorfer vonseiten der Spruchkammer am 20.09.1946 als „Mitläufer“ eingestuft wurde, gelang ihm keine Reintegration in den Lehrkörper der Friedrich-Alexander-Universität.
Diskussion Meggendorfer ließ sich – u. a. durch seine Erläuterungen zum Gesetz zur Verhütung erbkranken Nachwuchses – der Freiheit für selbstständiges geistiges Schaffen als Kern des akademischen Selbstverständnisses zumindest partiell berauben.
Schlussfolgerung Der vermehrte Einbezug ethischer Reflexionen in die psychiatrisch / psychosomatische Facharztausbildung kann den „Seelenarzt“ vor Instrumentalisierbarkeit schützen.
Neue Arzneimittel für Kleintiere 2019
Authors: Emmerich Ilka Ute 
Published: April 2020

ZusammenfassungIm Jahr 2019 kamen für Kleintiere 2 neue Wirkstoffe auf den deutschen Tierarzneimittelmarkt: das nicht steroidale, nicht die Cyclooxygenase hemmende Antiphlogistikum Grapiprant (Galliprant®) aus der Piprant-Klasse und das Diagnostikum für Kornealdefekte Fluorescein (Ophtorescein®), ein Xanthenfarbstoff. Ein Wirkstoff erhielt eine Tierartenerweiterung. So wurde das Antidiabetikum Protamin-Zink-Insulin humanen Ursprungs (ProZinc®) auch für Hunde zugelassen. Außerdem kamen eine neue Wirkstoffkombination (Fluralaner + Moxidectin), 5 Wirkstoffe (Acepromazin, Chloramphenicol, Dexamethason, Metronidazol, Torasemid) in einer neuen Darreichungsform, ein Wirkstoff (Lidocain) in einer neuen Anwendungsart und ein Wirkstoff (Apomorphin) in einer neuen Primärverpackung mit verlängerter Anbruchstabilität für Kleintiere auf den Markt.