bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ornithine capture by a translating ribosome controls bacterial polyamine synthesis
Authors: del Valle Alba Herrero , Seip Britta , Cervera-Marzal Iñaki , Sacheau Guénaël , Seefeldt A. Carolin , Innis C. Axel 
Published: April 2019

ABSTRACTPolyamines are essential metabolites that play an important role in cell growth, stress adaptation, and microbial virulence1–3. In order to survive and multiply within a human host, pathogenic bacteria adjust the expression and activity of polyamine biosynthetic enzymes in response to different environmental stresses and metabolic cues2. Here, we show that ornithine capture by the ribosome and the nascent peptide SpeFL controls polyamine synthesis in γ-proteobacteria by inducing the expression of the ornithine decarboxylase SpeF4, via a mechanism involving ribosome stalling and transcription antitermination. In addition, we present the cryo-EM structure of an Escherichia coli (E. coli) ribosome stalled during translation of speFL in the presence of ornithine. The structure shows how the ribosome and the SpeFL sensor domain form a highly selective binding pocket that accommodates a single ornithine molecule but excludes near-cognate ligands. Ornithine pre-associates with the ribosome and is then held in place by the sensor domain, leading to the compaction of the SpeFL effector domain and blocking the action of release factor RF1. Thus, our study not only reveals basic strategies by which nascent peptides assist the ribosome in detecting a specific metabolite, but also provides a framework for assessing how ornithine promotes virulence in several human pathogens.
Bacterial DNA induces the formation of heat-resistant disease-associated “Tetz-proteins” in human plasma
Authors: Tetz Victor , Tetz George V. 
Published: April 2019

AbstractOur study demonstrated for the first time that bacterial extracellular DNA (eDNA) can change the thermal behaviour of specific human plasma proteins, leading to an elevation of the heat-resistant protein fraction, as well as tode novoacquisition of heat-resistance. In fact, the majority of these proteins were not known to be heat-resistant and nor do they possess any prion-like domain. Proteins found to become heat-resistant following DNA exposure were named “Tetz-proteins”.Interestingly, plasma proteins that become heat-resistant following treatment with bacterial eDNA are known to be associated with cancer progression. Therefore, we analysed the heat-resistant proteome in the plasma of healthy subjects and in patients with pancreatic cancer and found that exposure to bacterial eDNA made the proteome of healthy subjects more similar to that of cancer patients. These findings open a discussion on the possible novel role of eDNA in disease development following its interaction with specific proteins, including those involved in multifactorial diseases such as cancer.
Focal adhesion kinase confers pro-migratory and anti-apoptotic properties and is a potential therapeutic target in Ewing sarcoma
Authors: Steinestel Konrad , Jansen Esther-Pia , Trautmann Marcel , Dirksen Uta , Rehkämper Jan , Mikesch Jan-Henrik , Gerke Julia S. , Orth Martin F. , Sannino Giuseppina , Wardelmann Eva , Grünewald Thomas G. P. , Hartmann Wolfgang 
Published: April 2019

ABSTRACTOncogenesis of Ewing sarcoma (EwS), the second most common malignant bone tumor of childhood and adolescence, is dependent on the expression of chimeric EWSR1-ETS fusion oncogenes, most often EWSR1-FLI1 (E/F).E/F expression leads to dysregulation of focal adhesions (FAs) enhancing the migratory capacity of EwS cells. Here we show that, in EwS cell lines and tissue samples, focal adhesion kinase (FAK) is expressed and phosphorylated at Y397 in an E/F-dependent way involving Ezrin. Employing different EwS cell as in vitro models, we found that key malignant properties of E/F are mediated via substrate-independent autophosphorylation of FAK on Y397. This phosphorylation results in enhanced FA formation, Rho-dependent cell migration, and impaired caspase-3-mediated apoptosis in vitro. Conversely, treatment with the FAK inhibitor Y15 enhanced caspase-mediated apoptosis and EwS cell migration, independent from the respective EWSR1-ETS fusion type, mimicking an anoikis-like phenotype. Our findings were confirmed in vivo using an avian chorioallantoic membrane (CAM) model. Our results provide a first rationale for the therapeutic use of FAK inhibitors to impair metastatic dissemination of EwS.
The ratio between centromeric proteins CENP-A and CENP-C maintains homeostasis of human centromeres
Authors: Melters Daniël P. , Rakshit Tatini , Bui Minh , Grigoryev Sergei A. , Sturgill David , Dalal Yamini 
Published: April 2019

AbstractThe centromere is the chromosomal locus that seeds the kinetochore, allowing for a physical connection between the chromosome and the mitotic spindle. At the heart of the centromere is the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle the constitutive centromere associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome dynamicsin vivois unknown. Here, we purify kinetochore associated native centromeric chromatin and analyze its biochemical features using a combinatorial approach. We report that kinetochore bound chromatin has strongly reduced DNA accessibility and a distinct stabilized nucleosomal configuration. Disrupting the balance between CENP-A and CENP-C result in reduced centromeric occupancy of RNA polymerase 2 and impairedde novoCENP-A loading on the centromeric chromatin fiber, correlating with significant mitotic defects. CENP-A mutants that restore the ratio rescue the mitotic defects. These data support a model in which CENP-C bound centromeric nucleosomes behave as a barrier to the transcriptional machinery and suggest that maintaining the correct ratio between CENP-A and CENP-C levels is critical for centromere homeostasis.
Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms
Authors: Rausch Philipp , Rühlemann Malte , Hermes Britt , Doms Shauni , Dagan Tal , Dierking Katja , Domin Hanna , Fraune Sebastian , Frieling Jakob von , Humeida Ute Henschel , Heinsen Femke-Anouska , Höppner Marc , Jahn Martin , Jaspers Cornelia , Kissoyan Kohar Annie B. , Langfeldt Daniela , Rehman Ateeqr , Reusch Thorsten B. H. , Röder Thomas , Schmitz Ruth A. , Schulenburg Hinrich , Soluch Ryszard , Sommer Felix , Stukenbrock Eva , Weiland-Bräuer Nancy , Rosenstiel Philip , Franke Andre , Bosch Thomas , Baines John F. 
Published: April 2019

AbstractBackgroundThe interplay between hosts and their associated microbiome is now recognized as a fundamental basis of the ecology, evolution and development of both players. These interdependencies inspired a new view of multicellular organisms as “metaorganisms”. The goal of the Collaborative Research Center “Origin and Function of Metaorganisms” is to understand why and how microbial communities form long-term associations with hosts from diverse taxonomic groups, ranging from sponges to humans in addition to plants.MethodsIn order to optimize the choice of analysis procedures, which may differ according to the host organism and question at hand, we systematically compared the two main technical approaches for profiling microbial communities, 16S rRNA gene amplicon- and metagenomic shotgun sequencing across our panel of ten host taxa. This includes two commonly used 16S rRNA gene regions and two amplification procedures, thus totaling five different microbial profiles per host sample.ConclusionWhile 16S rRNA gene-based analyses are subject to much skepticism, we demonstrate that many aspects of bacterial community characterization are consistent across methods and that metagenomic shotgun results are largely dependent on the employed pipeline. The resulting insight facilitates the selection of appropriate methods across a wide range of host taxa. Finally, by contrasting taxonomic and functional profiles and performing phylogenetic analysis, we provide important and novel insight into broad evolutionary patterns among metaorganisms, whereby the transition of animals from an aquatic to a terrestrial habitat marks a major event in the evolution of host-associated microbial composition.
Agreement between two large pan-cancer CRISPR-Cas9 gene dependency datasets
Authors: Dempster Joshua M. , Pacini Clare , Pantel Sasha , Behan Fiona M. , Green Thomas , Krill-Burger John , Beaver Charlotte M. , Younger Scott T. , Zhivich Victor , Najgebauer Hanna , Allen Felicity , Gonçalves Emanuel , Shepherd Rebecca , Doench John G. , Yusa Kosuke , Vazquez Francisca , Parts Leopold , Boehm Jesse S. , Golub Todd R. , Hahn William C. , Root David E. , Garnett Mathew J. , Iorio Francesco , Tsherniak Aviad 
Published: April 2019

AbstractGenome-scale CRISPR-Cas9 viability screens performed in cancer cell lines provide a systematic approach to identify cancer dependencies and new therapeutic targets. As multiple large-scale screens become available, a formal assessment of the reproducibility of these experiments becomes necessary. We analyzed data from recently published pan-cancer CRISPR-Cas9 screens performed at the Broad and Sanger institutes. Despite significant differences in experimental protocols and reagents, we found that the screen results are highly concordant across multiple metrics with both common and specific dependencies jointly identified across the two studies. Furthermore, robust biomarkers of gene dependency found in one dataset are recovered in the other. Through further analysis and replication experiments at each institute, we found that batch effects are driven principally by two key experimental parameters: the reagent library and the assay length. These results indicate that the Broad and Sanger CRISPR-Cas9 viability screens yield robust and reproducible findings.
Conservative and disruptive modes of adolescent change in brain functional connectivity
Authors: Váša František , Romero-Garcia Rafael , Kitzbichler Manfred G. , Seidlitz Jakob , Whitaker Kirstie J. , Vaghi Matilde M. , Kundu Prantik , Patel Ameera X. , Fonagy Peter , Dolan Raymond J. , Jones Peter B. , Goodyer Ian M. ,   the NSPN Consortium, Vértes Petra E. , Bullmore Edward T. 
Published: April 2019

AbstractAdolescent changes in human brain function are not entirely understood. Here we used multi-echo functional magnetic resonance imaging (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in N=298 healthy adolescents. Participants were aged 14-26 years and were scanned on two or more occasions at least 6 months apart. We found two distinct modes of age-related change in FC: “conservative” and “disruptive”. Conservative development was characteristic of primary cortex, which was strongly connected at 14 years and became even more connected in the period 14-26 years. Disruptive development was characteristic of association cortex, hippocampus and amygdala, which were not strongly connected at 14 years but became more strongly connected during adolescence. We defined the maturational index (MI) as the signed coefficient of the linear relationship between baseline FC (at 14 years,FC14) and adolescent change in FC (∆FC14−26). Disruptive systems (with negative MI) were functionally specialised for social cognition and autobiographical memory and were significantly co-located with prior maps of aerobic glycolysis (AG), AG-related gene expression, post-natal expansion of cortical surface area, and adolescent shrinkage of cortical depth. We conclude that human brain organization is disrupted during adolescence by the emergence of strong functional connectivity of subcortical nuclei and association cortical areas, representing metabolically expensive re-modelling of synaptic connectivity between brain regions that were not strongly connected in childhood. We suggest that this re-modelling process may support emergence of social skills and self-awareness during healthy human adolescence.
Morphogenesis of giant telomeric nuclear bodies in cancer cells with alternative lengthening of telomeres
Authors: Arimasu Yuu , Fujiwara Masachika , Ishii Jun , Chiba Tomohiro , Terado Yuichi , Shishido-Hara Yukiko , Kamma Hiroshi 
Published: April 2019

AbstractSome cancer cells lengthen their telomeres by alternative lengthening of telomeres (ALT); these are referred to as ALT cancer cells and do not express telomerase. The ALT mechanism involves the elongation of telomeric DNA repeats by homologous recombination. In interphase nuclei of ALT cancer cells, giant telomeres can be specifically observed by fluorescencein situhybridization (FISH) to detect telomeric repeats, and they are co-localized with promyelocytic-leukemia nuclear-bodies (PML-NBs). However, it how large telomeres specific to ALT and how they form a structural relation with PML-NBs. We refer to giant telomeres specific to interphase ALT cancer cells giant-telomeric nuclear-bodies (GT-NBs). To quantitatively define GT-NBs, we performed telomeric FISH of both interphase nuclei and metaphase chromosomes and analyzed telomere sizes by integrated FISH signals. The distributions of telomere sizes in telomerase-positive cells were similar in interphase nuclei and chromosomes. However, the distribution of telomere sizes in ALT cancer cells differed between interphase nuclei and chromosomes. Giant telomeres that were larger than those at chromosomal ends were only observed in interphase nuclei of ALT cancer cells. Accordingly, GT-NBs could be quantitatively defined as larger than the maximum size of telomeres at chromosomal ends. Furthermore, ALT cancer cells demonstrated fewer telomeric signals in interphase nuclei than in chromosomes. These findings indicate that GT-NBs could be formed by the aggregation of two or more telomeres at chromosomal ends. Furthermore, super-resolution microscopy showed that GT-NBs contain one or two PML-NBs. GT-NBs are considered aggregates of telomeres and could contain multiple sites of homologous recombination accompanied by PML-NBs. These findings may contribute to the development of therapeutic approaches for ALT cancer. (251 words)
Exploring the association of collaterals and vessel density using optical coherence tomography angiography in retinal vein occlusions
Authors: Lee Hee Eun , Wang Yiyang , Fayed Alaa E. , Fawzi Amani A. 
Published: April 2019

AbstractPurposeUsing optical coherence tomography angiography (OCTA) to characterize the types of collaterals in eyes with retinal vein occlusion (RVO) and further investigate their correlations with vessel densities of the superficial (SCP) and the deep capillary plexus (DCP).MethodsThis cross-sectional study included 25 eyes of 23 patients with RVO. 3 × 3 mm2 OCTA macular scans were used to quantify the parafoveal vessel density (VD) of the SCP and DCP, and to classify the collaterals into one of four types (true superficial, true deep, superficial diving, and foveal collateral). Poisson regression model was used to identify significant associations between parafoveal VD and collaterals. We further compared parafoveal VD between subgroups classified by the presence of specific collateral types based on the results of a clustering algorithm.Results16 of 25 eyes (64%) developed collaterals. Of the 43 collateral vessels analyzed, 12/19 (63%) true superficial collaterals developed in eyes with central RVO, while all 10 superficial diving collaterals (100%) developed in eyes with branch RVO. Located exclusively in the SCP, true superficial collaterals were all arteriovenous (A-V), while diving collaterals were all veno-venular (V-V). We found a significant negative correlation between SCP VD and the total number of collaterals (R2 = 0.648, P < 0.001) for the entire study cohort. Furthermore, BRVO eyes that developed superficial diving collaterals and CRVO eyes that developed true superficial collaterals demonstrated statistically significant decrease in SCP VD (P-value = 0.014) and DCP VD (P-value = 0.030), respectively, as compared to their counterparts.ConclusionOur data shows that decreased capillary perfusion in RVO is associated with the development of collaterals, while the RVO type largely dictates the type of collateral that ultimately develops.
Clinical evaluation of presepsin considering renal function
Authors: Miyoshi Masashi , Inoue Yusuke , Nishioka Mai , Ikegame Akishige , Nakao Takayuki , Nagai Koujirou 
Published: April 2019

AbstractPresepsin, a glycoprotein produced during bacterial phagocytosis, has attracted attention as a sepsis marker for bacterial infections. However, since presepsin is affected by renal function, there is a need to separate the evaluation criteria for diagnosis of healthy subjects from that of patients with renal disorder. In this study, we analyzed the influence of kidney function on presepsin concentrations and recalculated the reference range based on the findings. For this purpose, EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected and used for presepsin measurement by PATHFAST. Presepsin was found to be significantly correlated with creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845) and eGFRcys (r = 0.879).Furthermore, in patients with chronic kidney disease at different glomerular filtration rate stages, the presepsin levels showed a significant increasing trend with advancing glomerular filtration rate stage. The reference range, calculated by nonparametric method using a total of 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59–153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with some biomarkers of renal function, indicating that it is necessary to consider the influence of renal function in patients with renal impairment. Further, the recalculated reference range might be more useful for diagnosis and treatment of sepsis than the standard reference currently in use, which likely includes false high values.
Evaluating environmental and ecological landscape characteristics relevant to urban resilience across gradients of land-sharing-sparing and urbanity
Authors: Dennis Matthew , Scaletta Katherine L. , James Philip 
Published: April 2019

AbstractWithin urban landscape planning, debate continues around the relative merits of land-sparing (compaction) and land-sharing (sprawl) scenarios. Using part of Greater Manchester (UK) as a case-study, we present a landscape approach to mapping green infrastructure and variation in social-ecological-environmental conditions as a function of land sparing and sharing. We do so for the landscape as a whole as well as for areas of high and low urbanity. Results imply potential trade-offs between land-sparing-sharing scenarios relevant to characteristics critical to urban resilience such as landscape connectivity and diversity, air quality, surface temperature, and access to green space. These trade-offs may be particularly complex due to the parallel influence of patch attributes such as land-cover and size and imply that both ecological restoration and spatial planning have a role to play in reconciling tensions between land-sparing and sharing strategies.
Lifecycle profit analysis of prefabricated multi-active façades
Authors: Sundling Rikard , Olander Stefan , Wallentén Petter , Burke Stephen , Bernardo Ricardo , Blomsterberg Åke 
Published: April 2019

Purpose
The purpose of this paper is to identify appropriate concepts of multi-active façades for the renovation of multifamily buildings in Sweden and to determine which, if any, are financially viable.

Design/methodology/approach
A lifecycle profit (LCP) analysis was used to examine financial viability through a ten-step process, which included identifying concepts, assessing costs and prices, calculating the LCP and performing sensitivity analysis. Two existing buildings – one low rise and the other high rise – were used as reference models.

Findings
The findings were contradictory. Implementing any of the multi-active façade concepts on the high-rise building would be financially beneficial. The opposite was, however, the case for the low-rise building. Two factors causing this contradiction have been identified: the façade material before renovation and the size of the building.

Research limitations/implications
The study is limited to two case buildings situated in Sweden; however, similar buildings represent a significant amount of the existing building stock. Part of the purpose of the study is also to investigate the merits of LCP analysis to evaluate energy-efficient retrofitting. The study implicates the benefits and pitfalls of LCP analysis needed to be considered by researchers and practitioners alike.

Originality/value
The research findings contribute to the understanding of energy-efficient retrofitting of existing multifamily buildings based on prefabricated multi-active façade concepts.
A conceptual wearable monitoring system for physiological indices and clothing microclimate measurement
Authors: Hong Yan , Cao Xuechun , Chen Yan , Pan Zhijuan , Chen Yu , Zeng Xianyi 
Published: April 2019

Purpose
The purpose of this paper is to investigate physiological indices related to comfort and health condition, based on which corresponding electronic equipment are selected and applied. A wearable monitoring system using sensor and liquid crystal display (LCD) techniques are then designed. Sensors are used to collect and transmit recording required signals from the wearer. A microcomputer with the type of AT89C52 is used to record and analyze the collected data. LCD is applied to display the health and comfort condition of the wearer.

Design/methodology/approach
A novel wearable monitoring system for the measurement of physiological indices and clothing microclimate is proposed in this study in order to monitoring both health and comfort condition of the wearer.

Findings
The proposed system provides reference for the application of sensor and display technologies in the field of smart clothing, which can be further applied to infant and child care, health care, home entertainment, military and industry.

Originality/value
This paper, first, investigated a framework of a wearable monitoring system considering both comfort and health condition and summarized the related physiological indices. The requirements of both comfort and health condition monitoring are analyzed to select appropriate electronic elements.