bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of atypical circulating tumor cells with prognostic value in metastatic breast cancer patients
Authors: Lopresti Alexia , Boudin Laurys , Finetti Pascal , Garnier Séverine , Aulas Anaïs , Liberatoscioli Maria-Lucia , Cabaud Olivier , Guille Arnaud , de Nonneville Alexandre , Dacosta Quentin , Denicolai Emilie , Pakradouni Jihane , Goncalves Anthony , Birnbaum Daniel , Acquaviva Claire , Bertucci François , Mamessier Emilie 
Published: September 2020

ABSTRACTBackgroundCirculating tumor cells (CTCs) have a strong potential as a quasi-non-invasive tool to set up precision medicine strategy for cancer patients. Tremendous efforts have been made to develop the second-generation of “filtration-based” technologies to detect CTCs, revealing a surprising heterogeneity among those cells. Here, we performed the largest and simultaneous analysis of all atypical circulating tumor cells (aCTCs) detected with a filtration-based technology, in a cohort of metastatic breast cancer (mBC) patients, and correlated their presence with clinicopathological and survival data.MethodsThe PERMED-01 study enrolled patients with mBC refractory to systemic therapy. We prospectively analyzed aCTCs present at the time of inclusion in the study, using the Screencell®Cyto device (n=91). Subsets cut-offs were established and evaluated for correlation with clinicopathological data, including progression-free survival (PFS) and overall survival (OS).ResultsThe median number of aCTCs found in mBC was 8.3 per mL of blood. Three subsets of aCTCs, absent from controls, were observed in mBC patients: single (s-aCTCs), circulating tumor micro-emboli (CTM), and giant-aCTCs (g-aCTCs). The presence of g-aCTCs was associated with shorter PFS and OS in multivariate analyses. For 23 cases, the analysis was completed with advanced immunofluorescence staining and showed that CTM and g-aCTCs displayed a hybrid phenotype for epithelial and mesenchymal markers.ConclusionsThis study highlights the heterogeneity of aCTCs in mBC patients both at the cytomorphological and molecular levels when using a Screencell®Cyto device. It reveals the g-aCTC subset as a prognostic factor and a potential stratification tool that might help to orientate late-stage mBC patients’ therapeutic care.
Estimation of the Basic Reproduction Number of SARS-CoV-2 in Bangladesh Using Exponential Growth Method
Authors: Mahmud Riaz , Patwari H. M. Abrar Fahim 
Published: September 2020

AbstractObjectivesIn December 2019, a novel coronavirus (SARS-CoV-2) outbreak emerged in Wuhan, Hubei Province, China. Soon, it has spread out across the world and become an ongoing pandemic. In Bangladesh, the first case of novel coronavirus (SARS-CoV-2) was detected on March 8, 2020. Since then, not many significant studies have been conducted to understand the transmission dynamics of novel coronavirus (SARS-CoV-2) in Bangladesh. In this study, we estimated the basic reproduction number R0 of novel coronavirus (SARS-CoV-2) in Bangladesh.MethodsThe data of daily confirmed cases of novel coronavirus (SARS-CoV-2) in Bangladesh and the reported values of generation time of novel coronavirus (SARS-CoV-2) for Singapore and Tianjin, China, were collected. We calculated the basic reproduction number R0 by applying the exponential growth (EG) method. Epidemic data of the first 76 days and different values of generation time were used for the calculation.ResultsThe basic reproduction number R0 of novel coronavirus (SARS-CoV-2) in Bangladesh is estimated to be 2.66 [95% CI: 2.58-2.75], optimized R0 is 2.78 [95% CI: 2.69-2.88] using generation time 5.20 with a standard deviation of 1.72 for Singapore. Using generation time 3.95 with a standard deviation of 1.51 for Tianjin, China, R0 is estimated to be 2.15 [95% CI: 2.09-2.20], optimized R0 is 2.22 [95% CI: 2.16-2.29].ConclusionsThe calculated basic reproduction number R0 of novel coronavirus (SARS-CoV-2) in Bangladesh is significantly higher than 1, which indicates its high transmissibility and contagiousness.
A wake-up call - revealing the oversight of sleep physiology and related translational discrepancies in studies of rapid-acting antidepressants
Authors: Alitalo Okko , Saarreharju Roosa , Zarate Carlos A. , Kohtala Samuel , Rantamäki Tomi 
Published: October 2020

AbstractDepression and sleep problems go hand-in-hand, while clinical improvement often emerges along the normalization of sleep architecture and realignment of the circadian rhythm. Antidepressant effects of sleep deprivation and cognitive behavioral therapy targeted at insomnia further demonstrate the confluence of sleep and mood. Moreover, recent literature showing that ketamine influences many processes related to sleep-wake neurobiology, have led to novel hypotheses explaining rapid and sustained antidepressant effects. Surprisingly, studies addressing ketamine’s antidepressant effects have had a narrow focus on solely on pharmacological aspects and often ignore the role of physiology. To illustrate this discrepancy, we conducted a literature review on articles around rapid-acting antidepressants published between 2009-2019. A gross keyword check indicated overall ignorance of sleep in most studies. To investigate the topic closer, we focused on the most cited preclinical and clinical research papers. Circadian rhythm, timing of drug administration and behavioral tests relative to light cycles, sleep, and their potential association with experimental observations were mentioned only in a handful of the papers. Most importantly, in preclinical reports the treatments have been preferentially delivered during the inactive period, which is polar opposite to clinical practice and research. We hope this report serves as a wake-up call for sleep in the field and urges (re)examining rapid-acting antidepressant effects from the perspective of wake-sleep physiology.
Reconsider phase reconstruction in signals with dynamic periodicity from the modern signal processing perspective
Authors: Alian Aymen , Lo Yu-Lun , Shelley Kirk , Wu Hau-Tieng 
Published: October 2020

AbstractPhase is the most fundamental physical quantity when we study an oscillatory time series. There are many tools aiming to estimate phase, most of them are developed based on the analytic function model. Unfortunately, this approach might not be suitable for modern signals withintrinsic nonstartionary structure, including multiple oscillatory components, each with time-varying frequency, amplitude, and non-sinusoidal oscillation, e.g., biomedical signals. Specifically, due to the lack of consensus of model and algorithm, phases estimated from signals simultaneously recorded from different sensors for the same physiological system from the same subject might be different. This fact might challenge reproducibility, communication, and scientific interpretation and thus we need a standardized approach with theoretical support over a unified model. In this paper, after summarizing existing models for phase and discussing the main challenge caused by the above-mentioned intrinsic nonstartionary structure, we introduce theadaptive non-harmonic model (ANHM), provide a definition of phase calledfundamental phase, which is a vector-valued function describing the dynamics of all oscillatory components in the signal, and suggest a time-varying bandpass filter (tvBPF) scheme based on time-frequency analysis tools to estimate the fundamental phase. The proposed approach is validated with a simulated database and a real-world database with experts’ labels, and it is applied to two real-world databases, each of which has biomedical signals recorded from different sensors, to show how to standardize the definition of phase in the real-world experimental environment. Specifically, we report that the phase describing a physiological system, if properly modeled and extracted, is immune to the selected sensor for that system, while other approaches might fail. In conclusion, the proposed approach resolves the above-mentioned scientific challenge. We expect its scientific impact on a broad range of applications.
Soluble mannose receptor induces pro-inflammatory macrophage activation and metaflammation
Authors: Embgenbroich Maria , van der Zande Hendrik J.P. , Hussaarts Leonie , Schulte-Schrepping Jonas , Pelgrom Leonard R. , García-Tardón Noemí , Schlautmann Laura , Stoetzel Isabel , Händler Kristian , Lambooij Joost M. , Zawistowska-Deniziak Anna , Hoving Lisa , de Ruiter Karin , Wijngaarden Marjolein , Pijl Hanno , van Dijk Ko Willems , Everts Bart , van Harmelen Vanessa , Yazdanbakhsh Maria , Schultze Joachim L. , Guigas Bruno , Burgdorf Sven 
Published: October 2020

AbstractPro-inflammatory activation of macrophages in metabolic tissues is critically important in induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct, functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to a Src/Akt/NF-κB-mediated cellular reprogramming towards an inflammatory phenotype bothin vitroandin vivo.Remarkably, increased serum sMR levels were observed in obese mice and humans and directly correlated with body weight. Additionally, MR deficiency lowers pro-inflammatory macrophages in metabolic tissues and protects against hepatic steatosis and whole-body metabolic dysfunctions in high-fat diet-induced obese mice. Conversely, administration of sMR in lean mice increases serum pro-inflammatory cytokines, activates tissue macrophages and promotes insulin resistance. Altogether, our results reveal sMR as novel regulator of pro-inflammatory macrophage activation which could constitute a new therapeutic target for metaflammation and other hyperinflammatory diseases.
Reconfiguring primase DNA-recognition sequences by using a data-driven approach
Authors: Soffer Adam , Ifrach Morya , Ilic Stefan , Afek Ariel , Schussheim Hallel , Vilenchik Dan , Akabayov Barak 
Published: October 2020

ABSTRACTDNA-protein interactions are essential in all aspects of every living cell. Understanding of how features embedded in the DNA sequence affect specific interactions with proteins is challenging but important, since it may contribute to finding the means to regulate metabolic pathways involving DNA-protein interactions. Using a massive experimental benchmark dataset of binding scores for DNA sequences and a machine learning workflow, we describe the binding to DNA of T7 primase, as a model system for specific DNA-protein interactions. Effective binding of T7 primase to its specific DNA recognition sequences triggers the formation of RNA primers that serve as Okazaki fragment start sites during DNA replication.
Separation of coiled-coil structures in lamin A/C is required for elongation of the filament
Authors: Ahn Jinsook , Jeong Soyeon , Kang So-mi , Jo Inseong , Park Bum-Joon , Ha Nam-Chul 
Published: September 2020

AbstractIntermediate filaments (IFs) commonly have structural elements of a central α-helical coiled-coil domain consisting of coil 1a, coil 1b, coil 2, and their flanking linkers. Recently, crystal structure of a long lamin A/C fragment was determined and showed detailed features of a tetrameric unit. The structure further suggested a new binding mode between tetramers, designated eA22, where a parallel overlap of coil 1a and coil 2 is the key interaction. In this study, we investigated the biochemical effects of genetic mutations causing human diseases, focusing on the eA22 interaction. The mutant proteins exhibited either weakened or augmented interactions between coil 1a and coil 2. The ensuing biochemical results indicated that the interaction requires the separation of the coiled-coils in N-terminal of coil 1a and C-terminal of coil 2, coupled with the structural transition in the central α-helical rod domain. This study provides insight into the role of coil 1a as a molecular regulator in elongation of the IF proteins.
Carbon for nutrient exchange between the lycophyte,Lycopodiella inundataand Mucoromycotina ‘fine root endophytes’ is unresponsive to high atmospheric CO2concentration
Authors: Hoysted Grace A. , Kowal Jill , Pressel Silvia , Duckett Jeffrey G. , Bidartondo Martin I. , Field Katie J. 
Published: October 2020

Background and AimsNon-vascular plants associating with arbuscular mycorrhizal (AMF) and Mucoromycotina ‘fine root endophyte’ (MFRE) fungi derive greater benefits from their fungal associates under higher atmospheric [CO2] than ambient, however nothing is known about how changes in [CO2] affects MFRE function in vascular plants.MethodsWe measured movement of phosphorus (P), nitrogen (N) and carbon (C) between the lycophyte,Lycopodiella inundataand Mucoromycotina fine root endophyte fungi using33P-orthophosphate,15N-ammonium chloride and14CO2isotope tracers under ambient and elevated atmospheric [CO2] concentrations of 440 and 800 ppm, respectively.Key ResultsTransfer of33P and15N from MFRE to plant were unaffected by changes in [CO2]. There was a slight increase in C transfer from plant to MFRE under elevated [CO2].ConclusionsOur results demonstrate that the exchange of C-for-nutrients between a vascular plant and Mucoromycotina FRE is largely unaffected by changes in atmospheric [CO2]. Unravelling the role of MFRE in host plant nutrition and potential C-for-N trade changes between symbionts under varying abiotic conditions is imperative to further our understanding of the past, present and future roles of diverse plant-fungal symbioses in global ecosystems.
Genome-wide identification of novel genes involved inCorynebacterialescell envelope biogenesis usingCorynebacterium glutamicumas a model
Authors: de Sousa-d’Auria Célia , Constantinesco-Becker Florence , Constant Patricia , Tropis Maryelle , Houssin Christine 
Published: September 2020

AbstractCorynebacterialesareActinobacteriathat possess an atypical didermic cell envelope. One of the principal features of this cell envelope is the presence of a large complex made up of peptidoglycan, arabinogalactan and mycolic acids. This covalent complex constitutes the backbone of the cell wall and supports an outer membrane, called mycomembrane in reference to the mycolic acids that are its major component. The biosynthesis of the cell envelope ofCorynebacterialeshas been extensively studied, in particular because it is crucial for the survival of important pathogens such asMycobacterium tuberculosisand is therefore a key target for anti-tuberculosis drugs. In this study, we explore the biogenesis of the cell envelope ofCorynebacterium glutamicum, a non-pathogenicCorynebacteriales, which can tolerate dramatic modifications of its cell envelope as important as the loss of its mycomembrane. For this purpose, we used a genetic approach based on genome-wide transposon mutagenesis. We developed a highly effective immunological test based on the use of anti-arabinogalactan antibodies that allowed us to rapidly identify bacteria exhibiting an altered cell envelope. A very large number (10,073) of insertional mutants were screened by means of this test, and 80 were finally selected, representing 55 different loci. Bioinformatics analyses of these loci showed that approximately 60% corresponded to genes already characterized, 63% of which are known to be directly involved in cell wall processes, and more specifically in the biosynthesis of the mycoloyl-arabinogalactan-peptidoglycan complex. We identified 22 new loci potentially involved in cell envelope biogenesis, 76% of which encode putative cell envelope proteins. A mutant of particular interest was further characterized and revealed a new player in mycolic acid metabolism. Because a large proportion of the genes identified by our study is conserved inCorynebacteriales, the library described here provides a new resource of genes whose characterization could lead to a better understanding of the biosynthesis of the envelope components of these bacteria.
Tumor Necrosis Factor andSchistosoma mansoniegg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response
Authors: Takaki Kevin K. , Roca Francisco J. , Schramm Gabriele , Wilbers Ruud H. P. , Ittiprasert Wannaporn , Brindley Paul J. , Rinaldi Gabriel , Berriman Matthew , Ramakrishnan Lalita , Pagán Antonio J. 
Published: September 2020

AbstractInfections by schistosomes result in granulomatous lesions around parasite eggs entrapped within the host tissues. The host and parasite determinants of theSchistosoma mansoniegg-induced granulomatous response are areas of active investigation. Some studies in mice implicate Tumor Necrosis Factor (TNF) produced in response to the infection whereas others fail to find a role for it. In addition, in the mouse model, theS. mansonisecreted egg antigen omega-1 is found to induce granulomas but the underlying mechanism remains unknown. We have recently developed the zebrafish larva as a model to study macrophage recruitment and granuloma formation in response toSchistosoma mansonieggs. Here we use this model to investigate the mechanisms by which TNF and omega-1 shape the early granulomatous response. We find that TNF, specifically signaling through TNF receptor 1, is not required for macrophage recruitment to the egg and granuloma initiation but does mediate granuloma enlargement. In contrast, omega-1 mediates initial macrophage recruitment, with this chemotactic activity being dependent on its RNase activity. Our findings further the understanding of the role of these host- and parasite-derived factors and show that they impact distinct facets of the granulomatous response to the schistosome egg.
PYL8 ABA receptors ofPhoenix dactyliferaplay a crucial role in response to abiotic stress and are stabilized by ABA (118)
Authors: Garcia-Maquilon Irene , Coego Alberto , Lozano-Juste Jorge , Messerer Maxim , de Ollas Carlos , Julian Jose , Ruiz-Partida Rafael , Pizzio Gaston , Belda-Palazón Borja , Gomez-Cadenas Aurelio , Mayer Klaus F.X. , Geiger Dietmar , Alquraishi Saleh A. , Alrefaei Abdulwahed F. , Ache Peter , Hedrich Rainer , Rodriguez Pedro L. 
Published: October 2020

AbstractThe identification of those prevailing ABA receptors and molecular mechanisms that trigger drought adaptation in crops well adapted to harsh conditions such as date palm (Phoenix dactylifera, Pd) sheds light on plant-environment interactions. We reveal that PdPYL8-like receptors are predominantly expressed under abiotic stress, being Pd27 the most expressed receptor in date palm. Therefore, subfamily I PdPYL8-like receptors have been selected for ABA signaling during abiotic stress response in this crop. Biochemical characterization of PdPYL8-like and PdPYL1-like receptors revealed receptor- and ABA-dependent inhibition of PP2Cs, which triggers activation of thepRD29B-LUCreporter in response to ABA. PdPYLs efficiently abolish PP2C-mediated repression of ABA signaling, but loss of the Trp lock in the seed-specific AHG1-like phosphatase PdPP2C79 markedly impairs its inhibition by ABA receptors. Characterization ofArabidopsistransgenic plants that express PdPYLs shows enhanced ABA signaling in seed, root and guard cells. Specifically, Pd27 overexpressing (OE) plants showed lower ABA content and were more efficient than wild type to lower transpiration at negative soil water potential, leading to enhanced drought tolerance. Finally, PdPYL8-like receptors accumulate after ABA treatment, which suggests that ABA-induced stabilization of these receptors operates in date palm for efficient boosting of ABA signaling in response to abiotic stress.HighlightDate palm response to abiotic stress is triggered through PYL8-like ABA receptors that are stabilized by the hormone, which boosts plant adaptation to drought mediated by ABA.
Fitness dependence preserves selection for recombination across diverse mixed mating systems
Authors: Rybnikov Sviatoslav , Weissman Daniel B. , Hübner Sariel , Korol Abraham B. 
Published: October 2020

AbstractMeiotic recombination and the factors affecting its rate and fate in nature have inspired many theoretical studies in evolutionary biology. Classical theoretical models have inferred that non-zero recombination can be favoured under a rather restricted parameter range. Thus, the ubiquity of recombination in nature remains an open question. However, these models assumed constant (uniform) recombination with an equal rate across all individuals within the population. Models of fitness-dependent recombination, with the rate varying among genotypes according to their fitness have shown that such a strategy can often be favoured over the best constant recombination. Here we use simulations to show that across a range of mating systems with varying frequencies of selfing and clonality, fitness-dependent recombination is often favoured even when any non-zero constant recombination is disfavoured. This recombination-protecting effect of fitness dependence is strongest under intermediate rates of selfing or high rates of clonality.
Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA
Authors: Choi Heejin , Wang Zhengpin , Dean Jurrien 
Published: September 2020

AbstractpiRNAs are germline-specific, small non-coding RNAs required to maintain genome integrity and preserve RNA homeostasis during male gametogenesis. In murine adult testes, the highest levels of piRNAs are present in the pachytene stage of meiosis, but their mode of action and function remains incompletely understood. We previously reported that BTBD18 binds to 50 pachytene piRNA-producing loci. Here we show that spermatozoa in gene-edited mice lacking a BTBD18 targeted pachytene piRNA cluster on Chr18 have severe sperm head dysmorphology, poor motility, impaired acrosome exocytosis and are sterile. The absence of Chr18 piRNA results in an imbalance of heat shock proteins associated with renaturing proteins and the ubiquitin-proteasome system involved with protein degradation. The mutant phenotype arises from aberrant formation of proacrosomal vesicles, distortion of thetrans-Golgi network, and up-regulation of GOLGA2 associated with acrosome dysgenesis. Collectively, our findings reveal central role of pachytene piRNAs in controlling spermiogenesis and male fertility.
Mechanisms underlying proximity between oral commensal bacteria
Authors: Perera Dasith , McLean Anthony , Lopez Viviana Morillo , Cloutier-Leblanc Kaileigh , Almeida Eric , Cabana Kiana , Welch Jessica Mark , Ramsey Matthew 
Published: September 2020

AbstractComplex polymicrobial biofilm communities are abundant in nature particularly in the human oral cavity where their composition and fitness can affect health. While the study of these communities during disease is essential and prevalent, little is known about interactions within the healthy plaque community. Here we describe interactions between two of the most abundant species in this healthy microbiome,Haemophilus parainfluenzaeandStreptococcus mitis. We discovered thatH. parainfluenzaetypically exists adjacent to Mitis group streptococciin vivowith which it also positively correlated based on microbiome data. By comparingin vitrococulture data toex vivomicroscopy we revealed that this co-occurrence is density dependent and further influenced by H2O2production. We discovered thatH. parainfluenzaehas a more redundant, multifactorial response to H2O2than related organisms and that the integrity of this system enhances streptococcal fitness. We also show that Mitis group streptococci can act as anin vivosource of NAD forH. parainfluenzaeand that streptococciin vitroevoke patterns of carbon utilization fromH. parainfluenzaethat are similar to those observedin vivo. Our findings describe mechanistic interactions between two of the most abundant and prevalent members of healthy supragingival plaque that contribute to their survivalin vivo.