bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Milk Oligosaccharides modulate the risk for preterm birth in a microbiome dependent and independent manner
Authors: Pausan Manuela-Raluca , Kolovetsiou-Kreiner Vassiliki , Richter Gesa Lucia , Madl Tobias , Giselbrecht Elisabeth , Weiss Eva-Christine , Jantscher-Krenn Evelyn , Moissl-Eichinger Christine 
Published: June 2019

AbstractBackgroundPreterm birth is one of the leading causes of neonatal mortality. The causes for spontaneous preterm birth (PTB) are multifactorial and remain often unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with and without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood.ResultsWe identified several microbial signatures associated with short cervix, PTB and/or preterm contractions such asLactobacillus jensenii,L. gasseri,Ureaplasma sp. andGardnerella sp..Additionally, we observed associations between sialylated HMOs, in particular 3’-sialyllactose, with PTB, short cervix and increased inflammation and confirmed an influence of HMOs on the microbiome profile.ConclusionsIdentifying serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome-mediated, potentially driven by secretor-active HMOs in urine. Our results support current efforts to improve diagnostics and therapeutic strategies.
Guilty by association: How group-based (collective) guilt arises in the brain
Authors: Li Zhiai , Yu Hongbo , Zhou Yongdi , Kalenscher Tobias , Zhou Xiaolin 
Published: June 2019

AbstractPeople do not only feel guilty for transgressions of social norms/expectations that they are causally responsible for, but they also feel guilty for transgressions committed by those they identify as in-group (i.e., collective or group-based guilt). However, the neurocognitive basis of group-based guilt and its relation to personal guilt are unknown. To address these questions, we combined functional MRI with an interaction-based minimal group paradigm in which participants either directly caused harm to victims (i.e., personal guilt), or observed in-group members cause harm to the victims (i.e., group-based guilt). In three experiments (N = 90), we demonstrated that perceived shared responsibility with in-group members in the transgression predicted behavioral and neural manifestations of group-based guilt. Multivariate pattern analysis of the functional MRI data showed that group-based guilt recruited a similar brain representation in anterior middle cingulate cortex as personal guilt. These results have broaden our understanding of how group membership is integrated into social emotions.
Investigating the physical effects in bacterial therapies for avascular tumors
Authors: Mascheroni Pietro , Meyer-Hermann Michael , Hatzikirou Haralampos 
Published: June 2019

AbstractTumor-targeting bacteria elicit anticancer effects by infiltrating hypoxic regions, releasing toxic agents and inducing immune responses. Although current research has largely focused on the influence of chemical and immunological aspects on the mechanisms of bacterial therapy, the impact of physical effects is still elusive. Here, we propose a mathematical model for the anti-tumor activity of bacteria in avascular tumors that takes into account the relevant chemo-mechanical effects. We consider a time-dependent administration of bacteria and analyze the impact of bacterial chemotaxis and killing rate. We show that active bacterial migration towards tumor hypoxic regions provides optimal infiltration and that high killing rates combined with high chemotactic values provide the smallest tumor volumes at the end of the treatment. We highlight the emergence of steady states in which a small population of bacteria is able to constrain tumor growth. Finally, we show that bacteria treatment works best in the case of tumors with high cellular proliferation and low oxygen consumption.
Single-cell analysis of childhood leukemia reveals a link between developmental states and ribosomal protein expression as a source of intra-individual heterogeneity
Authors: Caron Maxime , St-Onge Pascal , Sontag Thomas , Wang Yu Chang , Richer Chantal , Ragoussis Ioannis , Sinnett Daniel , Bourque Guillaume 
Published: June 2019

AbstractChildhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer. It is characterized by bone marrow lymphoid precursors that acquire genetic alterations, resulting in disrupted maturation and uncontrollable proliferation. More than a dozen molecular subtypes of variable severity can be used to classify cALL cases. Modern therapy protocols currently cure 85-90% of cases, but other patients are refractory or will relapse and eventually succumb to their disease. To better understand these difficult cases, we investigated the nature and extent of intra-individual transcriptional heterogeneity of cALL at the cellular level by sequencing the transcriptomes of 39,375 individual cells in eight patients (six pre-B and two pre-T) and three healthy pediatric controls. We observed intra-individual transcriptional clusters in five out of the eight patients. Using pseudotime maturation trajectories of healthy B and T cells, we obtained the predicted developmental state of each leukemia cell and observed distribution shifts within patients. We showed that the predicted developmental states of these cancer cells are inversely correlated with ribosomal protein expression levels, which could be a common contributor to intra-individual heterogeneity in cALL patients.
Fighting the spread of antibiotic resistance with bacterial competence inhibitors
Authors: Domenech Arnau , Brochado Ana Rita , Sender Vicky , Hentrich Karina , Henriques-Normark Birgitta , Typas Athanasios , Veening Jan-Willem 
Published: June 2019

AbstractStreptococcus pneumoniaeis a commensal of the human nasopharynx, but it can also cause severe life-threatening antibiotic-resistant infections. Antibiotic consumption drives the spread of resistance by inducingS. pneumoniaecompetence leading to the uptake of exogenous DNA and horizontal gene transfer (HGT). We have identified potent inhibitors of competence, collectively called COM-blockers. We show that COM-blockers inhibit HGT by perturbing the proton motive force, thereby disrupting the export of the peptide that regulates competence. COM-blockers do not affect growth or compromise antibiotic activity at their active concentrations, and we did not observe any resistance development against them. Used as adjuvants of antibiotics, COM-blockers provide a strategy to reduce the spread of virulence factors and antibiotic resistance in human pathogens.One Sentence SummaryAntibiotic adjuvants block competence
Compounds without borders: a novel paradigm for quantifying complex odors and responses to scent-pollution in bumblebees
Authors: Sprayberry Jordanna D. H. 
Published: June 2019

AbstractBumblebees are critical pollinators whose populations have been experiencing troubling declines over the past several decades. Successful foraging improves colony fitness, thus understanding how anthropogenic influences modulate foraging behavior may aid conservation efforts. Odor pollution can have negative impacts on bumble- and honey-bees foraging behavior. However, given the vast array of potential scent contaminants, individually testing pollutants is an ineffective approach. The ability to quantitatively measure how much scent-pollution of a floral-odor bumblebees can tolerate would represent a paradigm shift in odor-pollution studies. Current statistical methods for analyzing complex odors have poor predictive power because statistically-derived odor-spaces are rewritten when new odors are added. This study presents an alternative method of analyzing complex odor blends based on the encoding properties of insect olfactory systems. This “Compounds Without Borders” (CWB) method vectorizes odors in a multidimensional space representing relevant functional group and carbon characteristics of their component odorants. A single vector can be built for any scent, which allows the angular distance between any two odors to be calculated – including a learned odor and its polluted counterpart. Data presented here indicate that CWB-angles are capable of both describing and predicting bumblebee odor-discrimination behavior: odor pairs with angular distances in the 20-29° range are generalized, while odor pairs over 30 degrees are differentiated. The neurophysiological properties underlying CWB-vectorization of odors are not unique to bumblebees; CWB-angle analysis of published data on a hawkmoth supports the idea that this method may have broader applications.
Pac1/LIS1 promotes an uninhibited conformation of dynein that coordinates its localization and activity
Authors: Marzo Matthew G. , Griswold Jacqueline M. , Markus Steven M. 
Published: June 2019

ABSTRACTCytoplasmic dynein is a minus end-directed microtubule motor that transports myriad cargos in various cell types and contexts. How dynein is regulated to perform all these activities with a high degree of spatial and temporal precision is unclear. Recent studies have revealed that human dynein-1 and dynein-2 can be regulated by a mechanism of autoinhibition, whereby intermolecular contacts limit motor activity. Whether this autoinhibitory mechanism is conserved throughout evolution, whether it can be affected by extrinsic factors, and its precise role in regulating cellular dynein activity remain unknown. Here, we use a combination of negative stain EM, single molecule motility assays, genetic, and cell biological techniques to show that the autoinhibitory conformation is conserved in budding yeast, and it plays an important role in coordinating dynein localization and function in cells. Moreover, we find that the Lissencephaly-related protein, LIS1 (Pac1 in yeast) plays an important role in regulating this autoinhibitory conformation of dynein. Specifically, our studies demonstrate that rather than inhibiting dynein motility, Pac1/LIS1 promotes dynein activity by stabilizing the uninhibited conformation, which ensures appropriate localization and activity of dynein in cells.
Movement patterns of free-roaming dogs on heterogeneous urban landscapes: implications for rabies control
Authors: Raynor Brinkley , De la Puente-León Micaela , Johnson Andrew , Díaz-Espinoza Elvis , Levy Michael Z. , Recuenco Sergio E. , Castillo-Neyra Ricardo 
Published: June 2019

AbstractIn 2015, a case of canine rabies in Arequipa, Peru indicated the re-emergence of rabies virus in the city. Despite mass dog vaccination campaigns across the city and reactive ring vaccination and other control activities around positive cases (e.g. elimination of unowned dogs), the outbreak has spread. Here we explore how the urban landscape of Arequipa affects the movement patterns of free-roaming dogs, the main reservoirs of the rabies virus in the area. We tracked 23 free-roaming dogs using Global Positioning System (GPS) collars. We analyzed the spatio-temporal GPS data using the time- local convex hull method. Dog movement patterns varied across local environments. We found that water channels, an urban feature of Arequipa that are dry most of the year, promote movement. Dogs that used the water channels move further, faster and more directionally than dogs that do not. Our findings suggest that water channels can be used by dogs as ‘highways’ to transverse the city and have the potential to spread disease far beyond the radius of control practices. Control efforts should focus on a robust vaccination campaign attuned to the geography of the city, and not limited to small-scale rings surrounding cases.
Tel1 activation by the MRX complex is sufficient for telomere length regulation but not for the DNA damage response inS. cerevisiae
Authors: Keener Rebecca , Connelly Carla J. , Greider Carol W. 
Published: June 2019

AbstractPrevious models suggested that regulation of telomere length inS. cerevisiaeby Tel1(ATM) and Mec1(ATR) parallel the established pathways regulating the DNA damage response. Here we provide evidence that telomere length regulation differs from the DNA damage response in both the Tel1 and Mec1 pathways. We found that Rad53 mediates a Mec1 telomere length regulation pathway but is dispensable for Tel1 telomere length regulation, whereas in the DNA damage response Rad53 is regulated by both Mec1 and Tel1. Using epistasis analysis with a Tel1 hypermorphic allele, Tel1-hy909, we found that the MRX complex is not required downstream of Tel1 for telomere elongation but is required downstream of Tel1 for the DNA damage response. Since models that invoke a required end processing event for telomerase elongation are primarily based on the yeast pathways, our data call for a re-examination of the requirement for telomere end processing in both yeast and mammalian cells.
Transcription reinitiation by recycling RNA polymerase that diffuses on DNA after releasing terminated RNA
Authors: Kang Wooyoung , Ha Kook Sun , Uhm Heesoo , Park Kyuhyong , Lee Ja Yil , Hohng Sungchul , Kang Changwon 
Published: June 2019

(Abstract)Despite extensive studies on transcription mechanisms, it is unknown how termination complexes are disassembled, especially in what order the components dissociate. Our single-molecule fluorescence study unveils that RNA transcript release precedes RNA polymerase (RNAP) dissociation from DNA template in bacterial intrinsic termination of transcription much more often than concurrent dissociation. As termination is defined by release of product RNA from transcription complex, the subsequent retention of RNAP on DNA constitutes a previously unidentified stage, termed here as ‘recycling.’ During the recycling stage, RNAPs one-dimensionally diffuse on DNA in downward and upward directions, and these RNAPs can initiate transcription again at nearby promoters in case of retaining a sigma factor. The efficiency of this event, termed here as ‘reinitiation,’ increases with supplement of a sigma factor. In summary, after releasing RNA product at intrinsic termination, recycling RNAP diffuses on DNA template for reinitiation most times.
Towards a Better Estimation of Functional Brain Network for Mild Cognitive Impairment Identification: A Transfer Learning View
Authors: Li Weikai , Zhang Limei , Qiao Lishan , Shen Dinggang 
Published: June 2019

AbstractMild cognitive impairment (MCI) is an intermediate stage of brain cognitive decline, associated with increasing risk of developing Alzheimer’s disease (AD). It is believed that early treatment of MCI could slow down the progression of AD, and functional brain network (FBN) could provide potential imaging biomarkers for MCI diagnosis and response to treatment. However, there are still some challenges to estimate a “good” FBN, particularly due to the poor quality and limited quantity of functional magnetic resonance imaging (fMRI) data from thetarget domain(i.e., MCI study). Inspired by the idea of transfer learning, we attempt to transfer information in high-quality data fromsource domain(e.g., human connectome project in this paper) into thetarget domaintowards a better FBN estimation, and propose a novel method, namely NERTL (Network Estimation via Regularized Transfer Learning). Specifically, we first construct a high-quality network “template” based on thesourcedata, and then use the template to guide or constrain thetargetof FBN estimation by a weightedl1-norm regularizer. Finally, we conduct experiments to identify subjects with MCI from normal controls (NCs) based on the estimated FBNs. Despite its simplicity, our proposed method is more effective than the baseline methods in modeling discriminative FBNs, as demonstrated by the superior MCI classification accuracy of 82.4% and the area under curve (AUC) of 0.910.
CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation
Authors: Zhong Yichen , Paudel Bishnu Prasad , Ryan Daniel P. , Low Jason K. K. , Franck Charlotte , Patel Karishma , Bedward Max J. , Payne Richard J. , van Oijen Antoine M. , Mackay Joel P. 
Published: June 2019

SummaryChromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and unclear if it is conserved among the four remodeller families. Here we use single-molecule assays to examine the mechanism of action of CHD4, which is part of the least well understood family of remodellers. We demonstrate that the binding energy for CHD4-nucleosome complex formation – even in the absence of nucleotide – triggers significant conformational changes in DNA at the entry side, effectively priming the system for remodelling. During remodelling, flanking DNA enters the nucleosome in a continuous, gradual manner but exits in concerted 4–6 base-pair steps. This decoupling of entry- and exit-side translocation suggests that ATP-driven movement of entry-side DNA builds up strain inside the nucleosome that is subsequently released at the exit side by DNA expulsion. We propose a mechanism for nucleosome sliding based on these and published data.
Orbitofrontal cortex promotes trial-by-trial learning of risky, but not spatial, biases
Authors: Constantinople Christine M. , Piet Alex T. , Bibawi Peter , Akrami Athena , Kopec Charles D. , Brody Carlos D. 
Published: June 2019

SummaryIndividual choices are not made in isolation but are embedded in a series of past experiences, decisions, and outcomes. The effects of past experiences on choices, often called sequential biases, are ubiquitous in perceptual and value-based decision-making, but their neural substrates are unclear. We trained rats to choose between explicitly cued guaranteed and probabilistic rewards in a task in which outcomes on each trial were independent. Behavioral variability often reflected the effects of previous trials, including increased willingness to take risks following risky wins, and spatial “win-stay/lose-shift” biases. Electrophysiological recordings from lateral orbitofrontal cortex (lOFC) revealed strong encoding of reward history and receipt, and optogenetic inhibition of lOFC during choice reporting eliminated rats’ increased preference for risk on subsequent trials following risky wins, but spared other sequential effects. Our data show that different sequential biases are neurally dissociable, and that the lOFC’s role in adaptive behavior promotes learning of more abstract, task-specific biases (here, biases for the risky option), but not spatial ones. These data are consistent with proposals that the OFC represents the animal’s location in an abstract representation of task states, and highlight the lOFC’s role in learning.
A bHLH interaction code controls bipotential differentiation and self-renewal in theDrosophilagut
Authors: Puig-Barbe Aleix , Dettmann Svenja , Nirello Vinicius Dias , Moor Helen , Azami Sina , Edgar Bruce A. , Varga-Weisz Patrick , Korzelius Jerome , de Navascués Joaquín 
Published: June 2019

ABSTRACTMultipotent adult stem cells balance self-renewal with differentiation into various cell types. How this balance is regulated at the transcriptional level is poorly understood. Here we show that a network of basic Helix-Loop-Helix (bHLH) transcription factors controls both stemness and bi-potential differentiation in theDrosophilaadult intestine. We find that homodimers of Daughterless (Da), homolog of mammalian E proteins, maintain self-renewal of intestinal stem cells (ISCs), antagonising the Enteroendocrine fate promoted by heterodimers of Da and Scute (Sc, homolog of ASCL). The HLH factor Extramacrochaetae (Emc, homologous to Id proteins) promotes absorptive differentiation by titrating Da and Sc. Emc prevents the committed absorptive progenitor from de-differentiating, underscoring the plasticity of these cells. Switching physical interaction partners in this way enables the active maintenance of stemness while priming stem cells for differentiation along two alternative fates. Such regulatory logic is likely operative in other bipotent stem cell systems.
Non-additive effects of changing the cytochrome P450 ensemble: incorporation of CYP2E1 into human liver microsomes and its impact on CYP1A2
Authors: Davydova Nadezhda Y. , Dangi Bikash , Maldonado Marc A. , Vavilov Nikita E. , Zgoda Victor G. , Davydov Dmitri R. 
Published: June 2019

AbstractThe aim of this study is to investigate the ability of ethanol-inducible CYP2E1 to interact with other cytochrome P450 species and affect the metabolism of their substrates. As a model system we used CYP2E1-enriched microsomes obtained by incorporation of purified CYP2E1 protein into HLM. Using the method based on homo-FRET in homo-oligomers of CYP2E1 labeled with BODIPY 577/618 maleimide we demonstrated that the interactions of CYP2E1 with microsomes result in dissociation of the protein homo-oligomers. The finding that this effect is much better pronounced in HLM as compared to the microsomes containing no P450 proteins indicates the formation of mixed oligomers of CYP2E1 with other P450 species that takes place in expense of dissociation of the homo-oligomers.Incorporation of CYP2E1 into HLM results in a multifold increase in the rate of metabolism of CYP2E1-specific substratesp-Nitrophenol (pNP) and Chlorzaxozone (CLZ). The rate of their oxidation remains proportional to the amount of incorporated CYP2E1 up to the content of 0.3-0.4 nmol/mg protein (or about 50% CYP2E1 in the P450 pool). These results demonstrate that the incorporated CYP2E1 becomes a fully-functional member of the P450 ensemble and do not exhibit any detectable functional differences with the endogenous CYP2E1 in HLM.Enrichment of HLM with CYP2E1 results in a pronounced alteration of the metabolism of 7-etoxy-4-cyanocoumarin (CEC), the substrate of CYP2C19 and CYP1A2, that suggests an important augmentation of the involvement of CYP1A2 in its metabolism. This effect goes together with a remarkable increase in the rate of dealkylation of CYP1A2-specific substrate 7-ethoxyresorufin by CYP2E1-enriched HLM. Furthermore, probing the interactions of CYP2E1 with model microsomes (Supersomes™) containing individual P450 enzymes we found that CYP2E1 efficiently interacts with CYP1A2, but lacks any ability to form complexes with CYP2C19. This finding goes inline with CYP2E1-induced redirection of the main route of CEC metabolism from CYP2C19 to CYP1A2.
Kinesin-8B controls basal body function and flagellum formation and is key to malaria parasite transmission
Authors: Zeeshan Mohammad , Ferguson David J. P. , Abel Steven , Burrrell Alana , Rea Edward , Brady Declan , Daniel Emilie , Delves Michael , Vaughan Sue , Holder Anthony A. , Le Roch Karine G. , Moores Carolyn A. , Tewari Rita 
Published: June 2019

AbstractEukaryotic flagella are conserved microtubule-based organelles that drive cell motility. Plasmodium, the causative agent of malaria, has a single flagellate stage: the male gamete in the mosquito. Three rounds of endomitotic division together with an unusual mode of flagellum assembly rapidly produce eight motile gametes. These processes are tightly coordinated but their regulation is poorly understood. To understand this important developmental stage, we studied the function and location of the microtubule-based motor kinesin-8B, using gene-targeting, electron microscopy and live cell imaging. Deletion of the kinesin-8B gene showed no effect on mitosis but disrupted 9+2 axoneme assembly and flagellum formation during male gamete development and also completely ablated parasite transmission. Live cell imaging showed that kinesin-8B-GFP did not colocalise with kinetochores in the nucleus but instead revealed dynamic, cytoplasmic localisation with the basal bodies and the assembling axoneme during flagellum formation. We thus uncovered an unexpected role for kinesin-8B in parasite flagellum formation that is vital for the parasite life cycle.