bluuebunny/crossref_metadata_2025_split huggingface dataset:
FastMLST: A multi-core tool for multilocus sequence typing of draft genome assemblies
Authors: Guerrero-Araya Enzo , Muñoz Marina , Rodríguez César , Paredes-Sabja Daniel 
Published: October 2020

ABSTRACTMultilocus Sequence Typing (MLST) is a precise microbial typing approach at the intra-species level for epidemiological and evolutionary purposes. It operates by assigning a sequence type (ST) identifier to each specimen, based on a combination of allelic sequences obtained for multiple housekeeping genes included in a defined scheme. The use of MLST has multiplied due to the availability of large numbers of genomic sequences and epidemiological data in public repositories. However, data processing speed has become problematic due to datasets’ massive size. Here, we present FastMLST, a tool that is designed to perform PubMLST searches using BLASTn and a divide-and-conquer approach. Compared with mlst, CGE/MLST, MLSTar, and PubMLST, FastMLST takes advantage of current multi-core computers to simultaneously type thousands of genome assemblies in minutes, reducing processing times by at least 4-fold and with more than 99.95% consistency.Availability and ImplementationThe source code, installation instructions and documentation are available athttps://github.com/EnzoAndree/FastMLST
Dynamic visualisation of million-tip trees: the OneZoom project
Authors: Wong Yan , Rosindell James 
Published: October 2020

AbstractThe complete tree of life is now available, but methods to visualise it are still needed to meet needs in research, teaching and science communication. Dynamic visualisation of million-tip trees requires many challenges in data synthesis, data handling and computer graphics to be overcome.Our approach is to automate data processing, synthesise data from a wide range of available sources, then to feed these data to a client-side visualisation engine in parts. We develop a way to store the whole tree topology locally in a highly compressed form, then dynamically populate metadata such as text and images as the user explores.The result is a seamless and smooth way to explore the complete tree of life, including images and metadata, even on relatively old mobile devices.The underlying methods developed have applications that transcend tree of life visualisation. For the whole complete tree, we describe automated ID mappings between well known resources without resorting to taxonomic name resolution, automated methods to collate sets of public domain representative images for higher taxa, and an index to measure public interest of individual species.The visualisation layout and the client user interface are both abstracted components of the codebase enabling other zoomable tree layouts to be swapped in, and supporting multiple applications including exhibition kiosks and digital art.After ten years of work, our tree of life explorer is now broadly complete, it has attracted nearly 1.5 million online users, and is backed by a novel long-term sustainability plan. We conclude our description of the OneZoom project by suggesting the next challenges that need to be solved in this field: extinct species and guided tours around the tree.
A structure-function substrate of memory for spatial configurations in medial and lateral temporal cortices
Authors: Tavakol Shahin , Li Qiongling , Royer Jessica , Vos de Wael Reinder , Larivière Sara , Lowe Alex , Paquola Casey , Jefferies Elizabeth , Hartley Tom , Bernasconi Andrea , Bernasconi Neda , Smallwood Jonathan , Bohbot Veronique , Caciagli Lorenzo , Bernhardt Boris 
Published: October 2020

AbstractPrior research has shown that structures of the mesiotemporal lobe, particularly the hippocampal-parahippocampal complex, are engaged in different forms of spatial cognition. Here, we developed a new paradigm, the Conformational Shift Spatial task (CSST), which examines the ability to encode and retrieve spatial relations between three unrelated items. This task is short, uses symbolic cues, and incorporates two difficulty levels and can be administered inside and outside the scanner. A cohort of 48 healthy young adults underwent the CSST, together with a set of validated behavioral measures and multimodal magnetic resonance imaging (MRI). Interindividual differences in CSST performance correlated with scores on an established spatial memory paradigm, but neither with episodic memory nor pattern separation performance, highlighting the specificity of the new measure. Analyzing high resolution structural MRI data, individuals with better spatial memory showed thicker medial as well as lateral temporal cortices. Functional relevance of these findings was supported by task-based functional MRI analysis in the same participants andad hocmeta-analysis. Exploratory resting-state functional MRI analyses centered on clusters of morphological effects revealed additional modulation of intrinsic network integration, particularly between lateral and medial temporal structures. Our work presents a novel spatial memory paradigm and supports an integrated structure-function substrate in the human temporal lobe. Task paradigms are programmed in python and made open access.
Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters
Authors: Piepenbrink Michael S. , Park Jun-Gyu , Oladunni Fatai S. , Deshpande Ashlesha , Basu Madhubanti , Sarkar Sanghita , Loos Andreas , Woo Jennifer , Lovalenti Phillip , Sloan Derek , Ye Chengjin , Chiem Kevin , Erdmann Nathaniel B. , Goepfert Paul A. , Truong Vu L. , Walter Mark R. , Martinez-Sobrido Luis , Kobie James J. 
Published: October 2020

AbstractSARS-CoV-2 infection results in viral burden in the upper and lower respiratory tract, enabling transmission and often leading to substantial lung pathology. Delivering the antiviral treatment directly to the lungs has the potential to improve lung bioavailability and dosing efficiency. As the SARS-CoV-2 Receptor Binding Domain (RBD) of the Spike (S) is increasingly deemed to be a clinically validated target, RBD-specific B cells were isolated from patients following SARS-CoV-2 infection to derive a panel of fully human monoclonal antibodies (hmAbs) that potently neutralize SARS-CoV-2. The most potent hmAb, 1212C2 was derived from an IgM memory B cell, has high affinity for SARS-CoV-2 RBD which enables its direct inhibition of RBD binding to ACE2. The 1212C2 hmAb exhibits in vivo prophylactic and therapeutic activity against SARS-CoV-2 in hamsters when delivered intraperitoneally, achieving a meaningful reduction in upper and lower respiratory viral burden and lung pathology. Furthermore, liquid nebulized inhale treatment of SARS-CoV-2 infected hamsters with as low as 0.6 mg/kg of inhaled dose, corresponding to approximately 0.03 mg/kg of lung deposited dose, mediated a reduction in respiratory viral burden that is below the detection limit, and mitigated lung pathology. The therapeutic efficacy achieved at an exceedingly low-dose of inhaled 1212C2 supports the rationale for local lung delivery and achieving dose-sparing benefits as compared to the conventional parenteral route of administration. Taken together, these results warrant an accelerated clinical development of 1212C2 hmAb formulated and delivered via inhalation for the prevention and treatment of SARS-CoV-2 infection.
The claustrum-medial prefrontal cortex network controls attentional set-shifting
Authors: Fodoulian Leon , Gschwend Olivier , Huber Chieko , Mutel Sophie , Salazar Rodrigo F. , Leone Roberta , Renfer Jean-Rodolphe , Ekundayo Kazadi , Rodriguez Ivan , Carleton Alan 
Published: October 2020

SUMMARYIn various mental disorders, dysfunction of the prefrontal cortex contributes to cognitive deficits. Here we studied how the claustrum (CLA), a nucleus sharing reciprocal connections with the cortex, may participate in these cognitive impairments. We show that specific ensembles of CLA and of medial prefrontal cortex (mPFC) neurons are activated during a task requiring cognitive control such as attentional set-shifting, i.e. the ability to shift attention towards newly relevant stimulus-reward associations while disengaging from irrelevant ones. CLA neurons exert a direct excitatory input on mPFC pyramidal cells, and chemogenetic inhibition of CLA neurons suppresses the formation of specific mPFC assemblies during attentional set-shifting. Furthermore, impairing the recruitment of specific CLA assemblies through opto/chemogenetic manipulations prevents attentional set-shifting. In conclusion, we propose that the CLA controls the reorganization of mPFC ensembles to enable attentional set-shifting, emphasizing a potential role of the CLA-mPFC network in attentional dysfunctions.
Connexin 43 confers chemoresistance through activating PI3K
Authors: Pridham Kevin J , Shah Farah , Sheng Kevin L , Guo Sujuan , Liu Min , Kanabur Pratik , Lamouille Samy , Lewis Gabrielle , Morales Marc , Jourdan Jane , Grek Christina L , Ghatnekar Gautam G , Varghese Robin , Kelly Deborah F , Gourdie Robert G , Sheng Zhi 
Published: October 2020

ABSTRACTCircumventing chemoresistance is crucial for effectively treating glioblastoma due to limited therapeutic options. The gap junction protein connexin 43 (Cx43) renders glioblastoma resistant to the frontline chemotherapy temozolomide; however, targeting Cx43 is difficult because mechanisms underlying Cx43-mediated chemoresistance remain elusive. Here we show that Cx43, but not other connexins, is highly expressed in glioblastoma and strongly correlates with poor patient prognosis and chemoresistance, making Cx43 the prime therapeutic target among all connexins. The intracellular carboxyl terminus of Cx43 binds to phosphatidylinositol 3-kinase (PI3K) catalytic subunit β (PIK3CB, also called PI3Kβ or p110β), thereby activating PI3K signaling independent of Cx43-channels and subsequently inducing temozolomide resistance. A combination of αCT1, a Cx43-targeting peptide inhibitor, and PIK3CB-selective inhibitors restores temozolomide sensitivityin vitroandin vivo. This study not only reveals novel mechanistic insights into chemoresistance in glioblastoma, but also demonstrates that targeting Cx43 and PIK3CB/p110β is an effective approach for overcoming chemoresistance.
Synthetic lethality between TP53 and ENDOD1
Authors: Tang Zizhi , Zeng Ming , Wang Xiaojun , Guo Chang , Yue Peng , Zhang Xiaohu , Lou Huiqiang , Chen Jun , Mu Dezhi , Kong Daochun , Carr Antony M. , Liu Cong 
Published: October 2020

AbstractThe atypical nuclease ENDOD1 functions with cGAS-STING in innate immunity. Here we identify a previously uncharacterized ENDOD1 function in DNA repair. ENDOD1 is enriched in the nucleus following H2O2treatment andENDOD1-/-cells show increased PARP chromatin-association. Loss of ENDOD1 function is synthetic lethal with homologous recombination defects, with affected cells accumulating DNA double strand breaks. Remarkably, we also uncover an additional synthetic lethality between ENDOD1 and p53. ENDOD1 depletion inTP53mutated tumour cells, or p53 depletion inENDOD1-/-cells, results in rapid single stranded DNA accumulation and cell death. BecauseTP53is mutated in ∼50% of tumours, ENDOD1 has potential as a wide-spectrum target for synthetic lethal treatments. To support this we demonstrate that systemic knockdown of mouseEndoD1is well tolerated and whole-animal siRNA against humanENDOD1restrainsTP53mutated tumour progression in xenograft models. These data identify ENDOD1 as a potential cancer-specific target for SL drug discovery.
Cell size homeostasis is maintained by a circuitry involving a CDK4-determined target size that programs the cell size-dependent activation of p38
Authors: Tan Ceryl , Ginzberg Miriam B. , Webster Rachel , Iyengar Seshu , Liu Shixuan , Concannon John , Wang Yuan , Auld Douglas S. , Jenkins Jeremy L. , Rost Hannes , Hilfinger Andreas , Derry W. Brent , Patel Nish , Kafri Ran 
Published: October 2020

SUMMARYWhile molecules that promote the growth of animal cells have been identified, the following question remains: How are growth promoting pathways regulated to specify a characteristic size for each of the different cell types? In 1975, Hartwell and Nurse suggested that in eukaryotes, cell size is determined by size checkpoints – mechanisms that restrict cell cycle progression from cells that aresmallerthan theirtarget size. Curiously, such checkpoint mechanisms imply a conceptual distinction between a cell’sactualsize and cell’stargetsize. In the present study, we materialize this conceptual distinction by describing experimental assays that discriminately quantify a cell’s target size value. With these assays, we show that a cell’s size and target size are distinct phenotypes that are subject to different upstream regulators. While mTORC1 promotes growth in cell size, our data suggests that a cell’s target size value is regulated by other pathways including FGFR3, ROCK2, and CDK4. For example, while rapamycin (an mTORC1 inhibitor) decreases cell size, rapamycin does not change the target size that is required for the G1/S transition. The CDK4/Rb pathway has been previously proposed as a putative regulator of target size. Yet, in lacking experimental means that discriminate perturbations of cell growth from perturbations that reprogram target size, such claims on target size were not validated. To investigate the functions of CDK4 in target size determination, we used genetic and chemical means to ‘dial’ higher and lower levels of CDK4 activity. These measurements identified functions of CDK4 on target size that are distinct from other G1 CDKs. UsingC. elegans, we further demonstrate that these influences of CDK4 on size determination functionin vivo. Finally, we propose a model whereby mTORC1, p38, and CDK4 cooperate in a manner that is analogous to the function of a thermostat. While mTORC1 promotes cellular growth as prompted by p38, CDK4 is analogous to the thermostatdialthat sets the critical target size associated with cell size homeostasis.
Synergistic anticancer effect of plasma-activated infusion and salinomycin by targeting autophagy and mitochondrial morphology
Authors: Ando Takashi , Suzuki-Karasaki Manami , Suzuki-Karasaki Miki , Ichikawa Jiro , Ochiai Toyoko , Yoshida Yukihiro , Haro Hirotaka , Suzuki-Karasaki Yoshihiro 
Published: October 2020

ABSTRACTNon-thermal atmospheric plasma (NTAP)-activated liquids have emerged as new promising anticancer agents because they preferentially injure malignant cells. Here, we report plasma-activated infusion (PAI) as a novel NTAP-based anti-neoplastic agent. PAI was prepared by irradiating helium NTAP to form a clinically approved infusion fluid. PAI dose-dependently killed malignant melanoma and osteosarcoma cell lines showed much lower cytotoxic effects on dermal and lung fibroblasts. We found that PAI and salinomycin (Sal), an emerging anti-cancer stem cell agent, mutually operated as adjuvants. Combined administration of PAI and Sal was much more effective than single agent application in reducing the growth and lung metastasis of osteosarcoma allografts with minimal adverse effects. Mechanistically, PAI explicitly induced necroptosis and increased the phosphorylation of receptor-interacting protein 1/3 in a rapid and transient manner. PAI also suppressed the ambient autophagic flux by activating the mammalian target of rapamycin pathway. PAI increased the phosphorylation of Raptor, Rictor, and p70-S6 kinase, along with decreased LC3-I/II expression. In contrast, Sal promoted autophagy. Moreover, Sal exacerbated the mitochondrial network collapse caused by PAI, resulting in aberrant clustering of fragmented mitochondrial in a tumor-specific manner. Our findings suggest that combined administration of PAI and Sal is a promising approach for treating these apoptosis-resistant cancers.
Collective nuclear behavior shapes bilateral nuclear symmetry for subsequent left-right asymmetric morphogenesis inDrosophila
Authors: Shin Dongsun , Nakamura Mitsutoshi , Morishita Yoshitaka , Eiraku Mototsugu , Yamakawa Tomoko , Sasamura Takeshi , Akiyama Masakazu , Inaki Mikiko , Matsuno Kenji 
Published: October 2020

SummaryProper organ development often requires nuclei to move to a specific position within the cell. To determine how nuclear positioning affects left-right (LR) development in theDrosophilaanterior midgut (AMG), we developed a surface-modeling method to measure and describe nuclear behavior at stages 13-14, captured in three-dimensional time-lapse movies. We describe the distinctive positioning and a novelcollective nuclear behaviorby which nuclei align LR-symmetrically along the anterior-posterior axis in the visceral muscles that overlie the midgut and are responsible for this organ’s LR-asymmetric development. Wnt4 signaling is crucial for the collective behavior and proper positioning of the nuclei, as are myosin II and LINC complex, without which the nuclei failed to align LR-symmetrically. The LR-symmetric positioning of the nuclei is important for the subsequent LR-asymmetric development of the AMG. We propose that the bilaterally symmetrical positioning of these nuclei may be mechanically coupled with subsequent LR-asymmetric morphogenesis.
Identification of silkworm hemocyte subsets and analysis of their response to BmNPV infection based on single-cell RNA sequencing
Authors: Feng Min , Xia Junming , Fei Shigang , Wang Xiong , Zhou Yaohong , Wang Pengwei , Swevers Luc , Sun Jingchen 
Published: October 2020

AbstractA wide range of hemocyte types exist in insects but a full definition of the different subclasses is not yet established. The current knowledge of the classification of silkworm hemocytes mainly comes from morphology rather than specific markers, so our understanding of the detailed classification, hemocyte lineage and functions of silkworm hemocytes is very incomplete.Bombyx morinucleopolyhedrovirus (BmNPV) is a representative member of the baculoviruses, which are a major pathogens that specifically infects silkworms and cause serious loss in sericulture industry. Here, we performed single-cell RNA sequencing (scRNA-seq) of silkworm hemocytes in BmNPV and mock-infected larvae to comprehensively identify silkworm hemocyte subsets and determined specific molecular and cellular characteristics in each hemocyte subset before and after viral infection. A total of 19 cell clusters and their potential marker genes were identified in silkworm hemocytes. Among these hemocyte clusters, clusters 0, 1, 2, 5 and 9 might be granulocytes (GR); clusters 14 and 17 were predicted as plasmatocytes (PL); cluster 18 was tentatively identified as spherulocytes (SP); and clusters 7 and 11 could possibly correspond to oenocytoids (OE). In addition, all of the hemocyte clusters were infected by BmNPV and some infected cells carried high viral-load in silkworm larvae at 3 day post infection (dpi). Interestingly, BmNPV infection can cause severe and diverse changes in gene expression in hemocytes. Cells belonging to the infection group mainly located at the early stage of the pseudotime trajectories. Furthermore, we found that BmNPV infection suppresses the immune response in the major hemocyte types. In summary, our scRNA-seq analysis revealed the diversity of silkworm hemocytes and provided a rich resource of gene expression profiles for a systems-level understanding of their functions in the uninfected condition and as a response to BmNPV.
Codependence in the Nephromyces species swarm depends on heterospecific bacterial endosymbionts
Authors: Paight Christopher , Hunter Elizabeth Sage , Lane Christopher E 
Published: October 2020

AbstractThe phylum Apicomplexa encompasses 6000 ubiquitous animal parasites, including Plasmodium, the most deadly human parasite on Earth. Anciently parasitic lineages, like apicomplexans, lose core metabolic pathways over time, as they evolve less costly scavenging mechanisms. The recent description of a mutualistic apicomplexan, Nephromyces, from deep within this parasitic group, opened the possibility of an evolutionary innovation that allowed an escape from a parasitic lifestyle. Nuclear genome data from Nephromyces, as well as the three bacterial symbionts that live within this species complex, demonstrate that the bacteria within Nephromyces contribute essential cofactors and amino acids that have enabled Nephromyces to abandon a parasitic lifestyle. Among these, bacterial lipoic acid appears to be a key cofactor for the reduction of virulence in Nephromyces. However, whereas we use FISH microscopy to reveal that each individual Nephromyces harbors no more than one endosymbiont type, no single bacterial endosymbiont can account for all missing metabolites. Based on the unique habitat of Nephromyces, as well as genomic, culturing, and wild population data, we conclude that Nephromyces has evolved as an extraordinary clade of codependent species, unlike any previously described.
Public attitudes to people with ASD: contact, knowledge and ethnicity
Authors: Gemegah Eli , Hartas Dimitra , Totsika Vasiliki 
Published: October 2020

PurposeThe increase in autism prevalence and presentation in the media suggests a rise in public awareness. This paper aims to explore what factors (contact, knowledge and ethnicity) may be associated to positive attitudes towards individuals with autism spectrum disorder (ASD).Design/methodology/approachAn online survey examined contact with and knowledge of ASD among Black, Asian and White ethnic groups to predict public attitudes to people with ASD.FindingsIn multiple regression models, the results suggested that the level of contact predicts positive attitudes towards autism when demographic factors were accounted. The level of knowledge about autism were significantly associated to attitudes, but not consistently when demographic factors were accounted. However, differences in knowledge and attitudes to people with ASD were identified amongst Black, Asian and White ethnic groups.Research limitations/implicationsThese findings have implications for policy and public health and education campaigns, including ensuring contact and knowledge of autism among the public.Originality/valueThese findings have implications for policy and public health and education campaigns, including ensuring contact and knowledge of autism among the public. Additionally, further effort is required to target public knowledge and attitudes to autism, particularly among ethnic groups. Institutional support tailored to encourage structured and unstructured contact across public domains such as education, health, social and care practices could effectively reduce prejudice between the public and people with ASD over time.
Addressing corporate social responsibility in corporations: a content analysis of Amazon's and Walmart's websites
Authors: Ertem-Eray Tugce 
Published: October 2020

PurposeThe purpose of this study is to analyze how Amazon and Walmart, two of the largest global companies, present the balance among their economic, social and environmental activities and construct their identities as good corporate citizens helping to create a sustainable world.Design/methodology/approachA content analysis methodology was applied to the companies' official websites in order to examine their corporate social responsibility (CSR) efforts. The Global Reporting Initiative (GRI) framework was used to provide coding categories.FindingsThe findings indicate that expectations and pressures from the public may help trigger companies to report their CSR efforts. In addition, this study also indicates that the triple bottom line TBL concept does not fully explain each companies' global CSR efforts.Originality/valueMost CSR studies have analyzed communication in only one country, rather than taking a global view. This study examines how Amazon and Walmart have constructed their identity as global corporate citizens and how they work to communicate their identity globally.