bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manganese depletion leads to multisystem changes in the transcriptome of the opportunistic pathogenStreptococcus sanguinis
Authors: Puccio Tanya , Kunka Karina S. , Zhu Bin , Xu Ping , Kitten Todd 
Published: August 2020

1AbstractStreptococcus sanguinisis a primary tooth colonizer and is typically considered beneficial due to its antagonistic relationship with the cariogenic pathogenStreptococcus mutans. However,S. sanguiniscan also act as an opportunistic pathogen should it enter the bloodstream and colonize a damaged heart valve, leading to infective endocarditis. Studies have implicated manganese acquisition as an important virulence determinant in streptococcal endocarditis. A knockout mutant lacking the primary manganese import system inS. sanguinis, SsaACB, is severely attenuated for virulence in anin vivorabbit model. Manganese is a known cofactor for several important enzymes inS. sanguinis, including superoxide dismutase, SodA, and the aerobic ribonucleotide reductase, NrdEF. To determine the effect of manganese depletion onS. sanguinis, we performed transcriptomic analysis on a ΔssaACBmutant grown in aerobic fermentor conditions after the addition of the metal chelator EDTA. Despite the broad specificity of EDTA, analysis of cellular metal content revealed a decrease in manganese, but not in other metals, that coincided with a drop in growth rate. Subsequent supplementation with manganese, but not iron, zinc, or magnesium, restored growth in the fermentor post-EDTA. Reduced activity of Mn-dependent SodA and NrdEF likely contributed to the decreased growth rate post-EDTA, but did not appear entirely responsible. With the exception of the Dps-like peroxide resistance gene,dpr, manganese depletion did not induce stress response systems. By comparing the transcriptome of ΔssaACBcells pre- and post-EDTA, we determined that manganese deprivation led to altered expression of diverse systems, including ethanolamine utilization, CRISPR/Cas, and a type IV pilus. Manganese depletion also led to an apparent induction of carbon catabolite repression in a glucose-independent manner. The combined results suggest that manganese limitation produces effects inS. sanguinisthat are diverse and complex, with no single protein or system appearing entirely responsible for the observed growth rate decrease. This study provides further evidence for the importance of this trace element in streptococcal biology. Future studies will focus on determining mechanisms for regulation, as the multitude of changes observed in this study indicate that multiple regulators may respond to manganese levels.
The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure
Authors: Chou Hsiang-Chen , Bhalla Kuhulika , Demerdesh Osama El , Klingbeil Olaf , Hanington Kaarina , Aganezov Sergey , Andrews Peter , Alsudani Habeeb , Chang Kenneth , Vakoc Christopher R. , Schatz Michael C. , McCombie W. Richard , Stillman Bruce 
Published: August 2020

AbstractThe Origin Recognition Complex (ORC) cooperates with CDC6, MCM2-7, and CDT1 to form pre- RC complexes at origins of DNA replication. Here we report tiling-sgRNA CRISPR screens that show that each subunit of ORC and CDC6 are essential in human cells. Using an auxin-inducible degradation system, stable cell lines were created that ablate ORC2 rapidly, revealing multiple cell division cycle phenotypes. The primary defect in the absence of ORC2 was cells encountering difficulty in initiating DNA replication or progressing through the cell division cycle due to reduced MCM2-7 loading onto chromatin in G1 phase. The nuclei of ORC2 deficient cells were also large, with decompacted heterochromatin. Some ORC2 deficient cells that completed DNA replication entered into, but never exited mitosis. ORC1 knockout cells also demonstrated extremely slow cell proliferation and abnormal cell and nuclear morphology. Thus, ORC proteins and CDC6 are indispensable for normal cellular proliferation and contribute to nuclear organization.
Consensus transcriptional states describe human mononuclear phagocyte diversity in the lung across health and disease
Authors: Peters Joshua M. , Blainey Paul C. , Bryson Bryan D. 
Published: August 2020

SUMMARYMonocytes, dendritic cells, and macrophages, commonly referred to as mononuclear phagocytes (MNPs), are innate immune cells capable of adopting diverse homeostatic and pathogenic phenotypes. Recent single-cell RNA-sequencing studies across many diseases in the lung have profiled this diversity transcriptionally, defining new cellular states and their association with disease. Despite these massive cellular profiling efforts, many studies have focused on defining myeloid dysfunction in specific diseases without identifying common pan-disease trends in the mononuclear phagocyte compartment within the lung. To address these gaps in our knowledge, we collate, process, and analyze 561,390 cellular transcriptomes from 12 studies of the human lung across multiple human diseases. We develop a computational framework to identify and compare dominant gene markers and gene expression programs and characterize MNP diversity in the lung, proposing a conserved dictionary of gene sets. Utilizing this reference, we efficiently identify disease-associated and rare MNP populations across multiple diseases and cohorts. Furthermore, we demonstrate the utility of this dictionary in characterizing a recently published dataset of bronchoalveolar lavage cells from COVID-19 patients and healthy controls which further reveal novel transcriptional shifts directly relatable to other diseases in the lung. These results underline conserved MNP transcriptional programs in lung disease, provide an immediate reference for characterizing the landscape of lung MNPs and establish a roadmap to dissecting MNP transcriptional complexity across tissues.
STAG2 loss-of-function affects short-range genomic contacts and modulates urothelial differentiation in bladder cancer cells
Authors: Richart Laia , Lapi Eleonora , Pancaldi Vera , Cuenca Mirabai , Carrillo-de-Santa Pau Enrique , Madrid-Mencía Miguel , Neyret-Kahn Hélène , Radvanyi François , Rodríguez Juan A. , Cuartero Yasmina , Serra François , Le Dily François , Valencia Alfonso , Marti-Renom Marc A. , Real Francisco X. 
Published: August 2020

ABSTRACTCohesin exists in two variants, containing either STAG1 or STAG2.STAG2is one of the most commonly mutated genes in human cancer, and a major bladder cancer tumor suppressor. Little is known about how its inactivation contributes to tumor development. Here, we analyze the genomic distribution of STAG1 and STAG2 and perform STAG2 loss-of-function experiments using RT112 bladder cancer cells; we then analyze the resulting genomic effects by integrating gene expression and chromatin interaction data. Cohesin-STAG2 is required for DNA contacts within topological domains, but not for compartment maintenance of domain boundary integrity. Cohesin-STAG2-mediated interactions are short-ranged and engage promoters and gene bodies with higher frequency than those mediated by cohesin-STAG1. STAG2 knockdown resulted in a modest but consistent down-regulation of the luminal urothelial differentiation signature, mirroring differences between STAG2-high and STAG2-low bladder tumors. Both lost and gained contacts were enriched among STAG1/STAG2 common sites as well as STAG2-enriched sites. Contacts lost upon depletion of STAG2 were significantly assortative, indicating their proximity at the 3D level, and were associated with changes in gene expression. Overall, our findings indicate that, in urothelial cells, STAG2 is required for the establishment and/or maintenance of DNA looping that, in turn, sustains the luminal differentiation program. This mechanism may contribute to the tumor suppressor function of STAG2 in bladder cancer.
Bioactivity of Aqueous Extract of Pulp ofCrysophyllum albidium(G. Don-Holl.) on Isoproterenol Treated Albino Rats
Authors: Morakinyo Adetoun , Akinlusi Ifeoluwani , Timileyin Ogundana , Adepoju Ayodeji , Akinpelu Bolajoko , Oyedepo Temitope , Oyedapo Oluboade 
Published: August 2020

ABSTRACTCardiovascular disorder is one of the causes of death globally. Quite a number of medicinal plants have been demonstrated to possess and exhibit beneficial effects on cardiovascular system throuhg their antioxidant properties. The study investigated thein vivoantioxidant properties of aqueousC. albidiumpulp extract on isoproterenol-induced cardiotoxicity in albino rats. Cardiotoxicity was induced in rats by subcutaneous injection of ISO (85 mg/kg bwt) into adult albino rats and treated with the extract (100 and 200 mg/kg bwt). The levels of nitrite, lipid peroxidation, reduced glutathione total protein and activities of glutathione peroxidase, catalase and superoxide dismutase were evaluated using standard methods. The concentration of total protein was also determined. Administration of ISO (85 mg/kg body weight) caused significant (p< 0.05) reduction in the antioxidant status of animals. The enzymatic and non-enzymatic antioxidants perturbed by the administration of ISO were restored in theC. albidiumtreated rats. The study concludes that the aqueous extract ofC. albidumpulp protected against Isoproterenol-induced cardiotoxicity in adult male Albino rats.
Identification of the keystone species in non-alcoholic fatty liver disease by causal inference and dynamic intervention modeling
Authors: Wu Dingfeng , Jiao Na , Zhu Ruixin , Zhang Yida , Gao Wenxing , Fang Sa , Li Yichen , Cheng Sijing , Tian Chuan , Lan Ping , Loomba Rohit , Zhu Lixin 
Published: August 2020

ABSTRACTObjectiveKeystone species are required for the integrity and stability of an ecological community, and therefore, are potential intervention targets for microbiome related diseases.DesignHere we describe an algorithm for the identification of keystone species from cross-sectional microbiome data of non-alcoholic fatty liver disease (NAFLD) based on causal inference theories and dynamic intervention modeling (DIM).ResultsEight keystone species in the gut of NAFLD, represented byP. loveana,A. indistinctusandD. pneumosintes, were identified by our algorithm, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome with 92.3% recovery. These keystone species regulate intestinal amino acids metabolism and acid-base environment to promote the growth of the butyrate-producing Lachnospiraceae and Ruminococcaceae species.ConclusionOur method may benefit microbiome studies in the broad fields of medicine, environmental science and microbiology.SUMMARYWhat is already known about this subject?Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disease whose pathogenesis remains unclear.Dysbiosis in the gut microbiota affects the initiation and development of NAFLD, but the mechanisms is yet to be established.Keystone species represent excellent candidate targets for gut microbiome-based interventions, as they are defined as the species required for the integrity and stability of the ecological system.What are the new findings?NAFLD showed significant dysbiosis in butyrate-producing Lachnospiraceae and Ruminococcaceae species.Microbial interaction networks were constructed by the novel algorithm with causal inference.Keystone species were identified form microbial interaction networks through dynamic intervention modeling based on generalized Lotka-Volterra model.Eight keystone species of NAFLD with the highest potential for restoring the microbial composition were identified.How might it impact on clinical practice in the foreseeable future?An algorithm for the identification of keystone species from cross-sectional microbiome data based on causal inference theories and dynamic intervention modeling.Eight keystone species in the gut of NAFLD, represented byP. loveana,A. indistinctusandD. pneumosintes, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome.Our method may benefit microbiome studies in the broad fields of medicine, environmental science and microbiology.
IgG antibody responses are preferential compared to IgM for use as serological markers for detecting recent exposure to Plasmodium vivax infection
Authors: Longley Rhea J , White Michael T , Brewster Jessica , Liu Zoe SJ , Bourke Caitlin , Takashima Eizo , Harbers Matthias , Tham Wai-Hong , Healer Julie , Chitnis Chetan E , Monteiro Wuelton , Lacerda Marcus , Sattabongkot Jetsumon , Tsuboi Takafumi , Mueller Ivo 
Published: August 2020

AbstractTo achieve malaria elimination, new tools are required to explicitly target Plasmodium vivax. Recently, a novel panel of P. vivax proteins were identified and validated as serological markers for detecting recent exposure to P. vivax within the last 9 months. In order to improve the sensitivity and specificity of these markers, IgM in addition to IgG antibody responses were assessed to a down-selected panel of 20 P. vivax proteins. IgM was tested using archival plasma samples from observational cohort studies conducted in malaria-endemic regions of Thailand and Brazil. IgM responses to these proteins generally had poorer classification performance than IgG.
Neutralizing antibody response in non-hospitalized SARS-CoV-2 patients
Authors: Ruetalo Natalia , Businger Ramona , Althaus Karina , Fink Simon , Ruoff Felix , Hamprecht Klaus , Flehmig Bertram , Bakchoul Tamam , Templin Markus F. , Schindler Michael 
Published: August 2020

AbstractThe majority of infections with SARS-CoV-2 are asymptomatic or mild without the necessity of hospitalization. It is of importance to reveal if these patients develop an antibody response against SARS-CoV-2 and to define which antibodies confer virus neutralization. We conducted a comprehensive serological survey of 49 patients with a mild course of disease and quantified neutralizing antibody responses against a clinical SARS-CoV-2 isolate employing human cells as targets.Four patients (8%), even though symptomatic, did not develop antibodies against SARS-CoV-2 and two other patients (4%) were only positive in one of the six serological assays employed. For the remainder, antibody response against the S-protein correlated with serum neutralization whereas antibodies against the nucleocapsid were poor predictors of virus neutralization. Regarding neutralization, only six patients (12%) could be classified as highly neutralizers. Furthermore, sera from several individuals with fairly high antibody levels had only poor neutralizing activity. In addition, employing a novel serological Western blot system to characterize antibody responses against seasonal coronaviruses, we found that antibodies against the seasonal coronavirus 229E might contribute to SARS-CoV-2 neutralization.Altogether, we show that there is a wide breadth of antibody responses against SARS-CoV-2 in patients that differentially correlate with virus neutralization. This highlights the difficulty to define reliable surrogate markers for immunity against SARS-CoV-2.
Epicardial slices: a 3D organotypic model for the study of epicardial activation and differentiation
Authors: Maselli D. , Matos R. S. , Johnson R. D. , Chiappini C. , Camelliti P. , Campagnolo P. 
Published: August 2020

AbstractThe epicardium constitutes an untapped reservoir for cardiac regeneration. Upon myocardial injury, the adult epicardium re-activates the embryonic program, leading to epithelial-to-mesenchymal transition, migration and differentiation. Despite some successes in harnessing the epicardial therapeutic potential by thymosin β4 (Tβ4) pre-treatment, further translational advancements are hampered by the paucity of representative experimental models. Here we apply innovative protocols to obtain living 3D organotypic slices from porcine hearts, encompassing the epicardial/myocardial interface. In culture, our slices preserve thein vivoarchitecture and functionality, presenting a continuous epicardium overlaying a healthy and connected myocardium. Upon Tβ4 treatment of the slices, the epicardial cells become activated upregulating embryonic and EMT genes and invading the myocardium where they differentiate towards the mesenchymal lineage. Our 3D organotypic model enables to investigate the reparative potential of the adult epicardium, offering a new tool to exploreex vivothe complex 3D interactions occurring within the native heart environment.
Computationally guided in-vitro vascular growth model reveals causal link between flow oscillations and disorganized neotissue
Authors: Van Haaften E.E. , Quicken S. , Huberts W. , Bouten C.V.C. , Kurniawan N.A. 
Published: August 2020

AbstractDisturbed shear stress is thought to be the driving factor of neointimal hyperplasia in blood vessels and grafts, for example in hemodialysis conduits. Despite the common occurrence of neointimal hyperplasia, however, the mechanistic role of shear stress is unclear. This is especially problematic in the context ofin situscaffold-guided vascular regeneration, a process strongly driven by the scaffold mechanical environment. To address this issue, we herein introduce an integrated numerical-experimental approach to reconstruct the graft-host response and interrogate the mechanoregulation in dialysis grafts. Starting from patient data, we numerically analyze the biomechanics at the vein-graft anastomosis of a hemodialysis conduit. Using this biomechanical data, we show in anin vitrovascular growth model that oscillatory shear stress, in the presence of cyclic strain, favors neotissue development by reducing the secretion of remodeling markers by vascular cells and promoting the formation of a dense and disorganized collagen network. These findings identify scaffold-based shielding of cells from oscillatory shear stress as a potential handle to inhibit neointimal hyperplasia in grafts.
What influences the innovation environment in BPO companies?
Authors: Ponciano Emanuel Soares , Amaral Creusa Sayuri Tahara 
Published: August 2020

PurposeThe purpose of this paper is to present the factors that form the innovation environment in the Business Process Outsourcing (BPO) sector, from a case study in a Brazilian multinational company operating in the Information and Communication Technologies (ICT) and BPO segment.Design/methodology/approachMinnesota Innovation Research Program (MIRP) questionnaire was adopted, aimed to environment conducive to innovation. It was applied to a sample of employees, from different hierarchical levels, who participated in an innovation training program developed and implemented by the organization. The data were analyzed to verify, in a simplified initial diagnosis, the influence of internal and external factors defined by MIRP in the company's innovation process.FindingsInnovation management process focuses predominantly on processes (71.4% of occurrences). As impact of the factors: results (88.9%), autonomy (76.3%), leadership (74.9%), resources (74.6%), internal relationship of the innovation group (73.1%), formalization (68.4%), processes (64.5%), relationship effectiveness (63.7%), external relationship of the innovation group (63.2%) and dependence on external resources (52.6%). There was confirmation that the innovation program of company is effective and that the culture of innovation is institutionalized.Research limitations/implicationsA crossing of supplementary information could reveal some significant difference in the perception of the innovative culture and performance of the innovation processes between distinguished profiles.Practical implicationsBetter guidance for management of ICT/BPO companies in an Open Innovation paradigm.Social implicationsBetter relationship among the actors of an Open Innovation industry arrangement.Originality/valueImprovement of the innovation process can occur through a greater focus on Open Innovation.
Design cybernetics in support of cross-disciplinary collaboration: educating the next generation of Chinese architects and structural engineers
Authors: Herr Christiane M. 
Published: August 2020

Purpose
This paper offers design cybernetics as a theoretical common ground to bridge diverging approaches to design as they frequently occur in collaborative design projects. Focusing on the education of architects and structural engineers in China, the paper examines how compatible approaches to design can be established in both disciplines.

Design/methodology/approach
The paper analyses relevant literature as well as observations from Chinese practice and academia. Design cybernetics is introduced and examined as a basis for establishing shared narratives to support cross-disciplinary collaborations involving architects and structural engineers.

Findings
Design cybernetics offers a body of vocabulary and a rich resource of strategies to address applied designing across design-oriented disciplines such as architecture and science-based disciplines such as structural engineering. The meta perspective of design cybernetics also provides a basis for the implementation of pedagogy supporting cross-disciplinary collaboration in applied design.

Research limitations/implications
The scope of the paper is limited to the examination of the theoretical framing as well as the implementation of pedagogy in the cultural and geographical context of China.

Practical implications
The paper outlines several design cybernetic strategies for pedagogy in support of cross-disciplinary collaborative design processes and illustrates their implementation in applied design education.

Originality/value
Addressing a significant and persistent gap between the two disciplines of architecture and structural engineering in the context of Chinese building practice, this paper examines the particularities of this context and presents an educational approach to support cross-disciplinary collaboration that has value in and beyond the context of China.
Barriers and facilitators to ex-service personnel obtaining employment within social care roles with older people: a scoping review
Authors: Manthorpe Jill , Bramley Stephanie 
Published: August 2020

PurposeThis purpose of this paper is to review evidence about the barriers and facilitators to ex-service personnel obtaining employment within social care roles. Social care has long-standing, well-recognised problems of staff recruitment and retention. Policymakers and employers are exploring if there are untapped sources of potential employees. Some ex-service personnel may be interested in exploring a move to social care work with older people but may face barriers to such a move which may need to be addressed.Design/methodology/approachDatabases and grey literature were searched systematically to provide an overview of evidence on this topic. In total, 23 articles were included in the review.FindingsA narrative analysis revealed barriers to ex-service personnel obtaining employment within social care not only related to their previous occupation, health status and identity but also facilitators related to the sector’s severe recruitment challenges and the transferable skills of ex-service personnel. Evidence suggests that learning from health services may be highly relevant and transferable.Research limitations/implicationsThis review was confined to English language studies published between 2008 and 2018. Few mentioned specific user or client groups.Originality/valueThis review identified evidence suggesting that learning from health services may be highly relevant and transferable to the social care sector so as to facilitate the transition of more ex-service personnel into social care work with older people.