bluuebunny/crossref_metadata_2025_split huggingface dataset:
SP1 and STAT3 functionally synergize to induce the RhoU small GTPase and a subclass of non-canonical WNT responsive genes correlating with poor prognosis in breast cancer
Authors: Monteleone Emanuele , Orecchia Valeria , Corrieri Paola , Schiavone Davide , Avalle Lidia , Moiso Enrico , Savino Aurora , Molineris Ivan , Provero Paolo , Poli Valeria 
Published: August 2018

ABSTRACTBreast cancer is a complex disease in which heterogeneity makes clinical management very challenging. Although breast cancer subtypes classified according to specific molecular features are associated to better or worse prognosis, the identification of specific markers predicting disease outcome within the single subtypes still lags behind. Both the non-canonical WNT and the STAT3 pathways are often constitutively activated in breast tumors, and both can induce the small GTPase RhoU gene transcription. Here we show that RhoU transcription can be triggered by both canonical and non-canonical WNT ligands via the activation of JNK and the recruitment of the SP1 transcription factor to the RhoU promoter, identifying for the first time SP1 as a JNK-dependent mediator of WNT signaling. RhoU down-regulation by silencing or treatment with JNK, SP1 or STAT3 inhibitors lead to impaired cell migration in basal-like MDA-MB-231 cells, which display constitutive activation of both the non-canonical WNT and STAT3 pathways. These data suggest that STAT3 and SP1 can cooperate to induce high RhoU expression and enhance migration of breast cancer cells.In vivobinding of both factors characterizes a group of SP1/STAT3 responsive genes belonging to the non-canonical WNT and the IL-6/STAT3 pathways. High expression of this signature is significantly correlated with poor prognosis across all profiled patients. Thus, concomitant binding of both STAT3 and SP1 defines a subclass of genes contributing to breast cancer aggressiveness, suggesting the relevance of developing novel targeted therapies combining inhibitors of the STAT3 and WNT pathways or of their downstream mediators.Novelty and ImpactThe WNT and STAT3 pathways are often activated in breast tumors, but whether they can cooperate towards aggressiveness is not presently known. Here the authors show that WNT ligands can elicit the activation of the transcription factor SP1, which cooperates with STAT3 to induce a subset of non-canonical WNT and IL-6/STAT3 genes. Expression of this gene signature correlates with bad prognosis in breast cancer, suggesting coordinated interference with both TFs as a novel therapeutic option.
Genome-wide chromatin accessibility and transcriptome profiling show minimal epigenome changes and coordinated transcriptional dysregulation of hedgehog signaling in Danforth’s short tail mice
Authors: Orchard Peter , White James S. , Thomas Peedikayil E. , Mychalowych Anna , Kiseleva Anya , Hensley John , Allen Benjamin , Parker Stephen C. J. , Keegan Catherine E. 
Published: August 2018

AbstractDanforth’s short tail(Sd)mice provide an excellent model for investigating the underlying etiology of human caudal birth defects, which affect 1 in 10,000 live births.Sdanimals exhibit aberrant axial skeleton, urogenital, and gastrointestinal development similar to human caudal malformation syndromes including urorectal septum malformation, caudal regression, VACTERL association, and persistent cloaca. Previous studies have shown that theSdmutation results from an endogenous retroviral (ERV) insertion upstream of thePtf1agene resulting in its ectopic expression at E9.5. Though the genetic lesion has been determined, the resulting epigenomic and transcriptomic changes driving the phenotype have not been investigated. Here, we performed ATAC-seq experiments on isolated E9.5 tailbud tissue, which revealed minimal changes in chromatin accessibility inSd/Sdmutant embryos. Interestingly, chromatin changes were localized to a small interval adjacent to theSdERV insertion overlapping a knownPtf1aenhancer region, which is conserved in mice and humans. Furthermore, mRNA-seq experiments revealed increased transcription of PTF1A target genes and, importantly, downregulation of hedgehog pathway genes. Reduced sonic hedgehog (SHH) signaling was confirmed by in situ hybridization and immunofluorescence suggesting that theSdphenotype results, in part, from downregulated SHH signaling. Taken together, these data demonstrate substantial transcriptome changes in theSdmouse, and indicate that the effect of the ERV insertion onPtf1aexpression may be mediated by increased chromatin accessibility at a conservedPtf1aenhancer. We propose that human caudal dysgenesis disorders may result from dysregulation of hedgehog signaling pathways.
Early and Late Effects of Maternal Experience on Hippocampal Neurogenesis, Microglia, and the Circulating Cytokine Milieu
Authors: Eid Rand S , Chaiton Jessica A , Lieblich Stephanie E , Bodnar Tamara S , Weinberg Joanne , Galea Liisa AM 
Published: August 2018

AbstractThe maternal brain displays considerable plasticity, and motherhood is associated with changes in affective and cognitive function. Motherhood can alter the trajectory of brain ageing, including modifications to neuroplasticity and cognition. Here, we investigated the short- and long-term effects of motherhood on hippocampal neurogenesis, microglial density and morphology, and circulating cytokines, domains known to be altered with age and implicated in cognition and mood. Female rats were bred then euthanized during gestation or at various postpartum timepoints, culminating in middle age, and nulliparous rats served as age-matched controls. Hippocampal neurogenesis was significantly suppressed during gestation and the postpartum period. Interestingly, neurogenesis declined significantly in middle-aged nulliparous rats, but increased in primiparous rats across the same period. Transient postpartum adaptations to the neuroimmune environment of the hippocampus were evidenced, as Iba-1-immunoreactive microglia assumed a de-ramified morphology followed by increased density. Intriguingly, ageing-related changes in circulating cytokines were dependent on parity. These adaptations in neurogenic and immune processes may have ramifications for maternal mood and cognition across the peripartum period and beyond.
Molecular bases for the constitutive photomorphogenic phenotypes in Arabidopsis
Authors: Pham Vinh Ngoc , Xu Xiaosa , Huq Enamul 
Published: August 2018

Summary statementStrikingly similar morphological and gene expression phenotypes among cop1, spaQ and pifQ mutants suggest that the cop phenotype of the cop1 and spaQ mutants might be due in part to a reduced level of PIFsAbstractThe transition from skotomorphogenesis to photomorphogenesis is regulated in part by COP1/SPA complex and PIFs in Arabidopsis. The constitutive photomorphogenic (cop) phenotypes of the cop1 and spaQ mutants were shown to be due to a high abundance of the positively acting transcription factors. Here we show that the four major PIF proteins are unstable in cop1 mutant, and an overexpression of P1F1, P1F3, P1F4 and P1F5 suppresses the cop1 phenotypes in the dark. A comparison of the transcriptome data among cop1, spaQ and pifQ reveals remarkably overlapping gene expression profiles with a preferential regulation of the PIF direct target genes. Additionally, HFR1 strongly inhibits the in vivo binding and transcriptional activation activity of PIF1 in the dark. Taken together, these data suggest that the cop phenotypes of the cop1 and spaQ mutants might be due to a combination of the reduced level of PIFs, increased level of the positive factors (e.g., HY5/HFR1 and others), and the HFR1-mediated inhibition of PIF targeted gene expression in the dark.
Cholinergic Midbrain Afferents Modulate Striatal Circuits and Shape Encoding of Action Control
Authors: Dautan Daniel , Huerta-Ocampo Icnelia , Valencia Miguel , Kondabolu Krishnakanth , Gerdjikov Todor V. , Mena-Segovia Juan 
Published: August 2018

SummaryAssimilation of novel strategies into a consolidated action repertoire is a crucial function for behavioral adaptation and cognitive flexibility. Acetylcholine in the striatum plays a pivotal role in such adaptation and its release has been causally associated with the activity of cholinergic interneurons. Here we show that the midbrain, a previously unknown source of acetylcholine in the striatum, is a major contributor to cholinergic transmission in the striatal complex. Neurons of the pedunculopontine and laterodorsal tegmental nuclei synapse with striatal cholinergic interneurons and give rise to excitatory responses that, in turn, mediate inhibition of spiny projection neurons. Inhibition of acetylcholine release from midbrain terminals in the striatum impairs action shifting and mimics the effects observed following inhibition of acetylcholine release from striatal cholinergic interneurons. These results suggest the existence of two hierarchically-organized modes of cholinergic transmission in the striatum where cholinergic interneurons are modulated by cholinergic neurons of the midbrain.
Magnaporthe oryzae SMO1encodes a Ras GTPase-activating protein required for spore morphology, appressorium function and rice blast disease
Authors: Kershaw Michael J. , Basiewicz Magdalena , Soanes Darren M. , Yan Xia , Ryder Lauren S. , Csukai Michael , Valent Barbara , Talbot Nicholas J. 
Published: August 2018

AbstractThe pathogenic life cycle of the rice blast fungusMagnaporthe oryzaeinvolves a series of morphogenetic changes, essential for its ability to cause disease. Thesmomutation was identified more than twenty-five years ago and affects the shape and development of diverse cell types inM. oryzae,including conidia, appressoria and asci. All attempts to clone theSMO1gene by map-based cloning and/or complementation, have failed over many years. Here, we report the identification ofSMO1by a combination of bulk segregant analysis and comparative genome analysis.SMO1encodes a GTPase-activating protein (GAP), which regulates Ras signalling during infection-related development. Targeted deletion ofSMO1results in abnormal, non-adherent conidia, impaired in their production of spore tip mucilage. Smo1 mutants also develop smaller appressoria, with a severely reduced capacity to infect rice plants.SMO1is necessary for organisation of microtubules and for septin-dependent remodelling of the F-actin cytoskeleton at the appressorium pore. Smo1 physically interacts with components of the Ras2 signaling complex, and a range of other signalling and cytoskeletal components, including the four core septins.SMO1is therefore necessary for regulation of RAS activation required for conidial morphogenesis and septin-mediated plant infection.
Interpretable genotype-to-phenotype classifiers with performance guarantees
Authors: Drouin Alexandre , Letarte Gaël , Raymond Frédéric , Marchand Mario , Corbeil Jacques , Laviolette François 
Published: August 2018

ABSTRACTUnderstanding the relationship between the genome of a cell and its phenotype is a central problem in precision medicine. Nonetheless, genotype-to-phenotype prediction comes with great challenges for machine learning algorithms that limit their use in this setting. The high dimensionality of the data tends to hinder generalization and challenges the scalability of most learning algorithms. Additionally, most algorithms produce models that are complex and difficult to interpret. We alleviate these limitations by proposing strong performance guarantees, based on sample compression theory, for rule-based learning algorithms that produce highly interpretable models. We show that these guarantees can be leveraged to accelerate learning and improve model interpretability. Our approach is validated through an application to the genomic prediction of antimicrobial resistance, an important public health concern. Highly accurate models were obtained for 12 species and 56 antibiotics, and their interpretation revealed known resistance mechanisms, as well as some potentially new ones. An open-source disk-based implementation that is both memory and computationally efficient is provided with this work. The implementation is turnkey, requires no prior knowledge of machine learning, and is complemented by comprehensive tutorials.
Effects of the anesthetic MS-222 on silver pomfret (Pampus argenteus) juveniles under aquaculture treatment stresses
Authors: Yu Na , Cao Xiaohuan , Wang Yajun , Kuang Siwen , Hu Jiabao , Yang Yang , Xu Shanliang , Zhang Man , Sun Yibo , Gu Weiwei , Yan Xiaojun 
Published: August 2018

AbstractThe silver pomfret (Pampus argenteus) is a major economically important marine fish in China. However, P. argenteus is sensitive to many stress factors and susceptible to injury. This problem could be resolved using anesthesia. We determined the lowest effective dose (LED) of tricaine methanesulfonate (MS-222) and assessed the longest safe deep anesthesia time and effect after aquaculture treatment stresses. P. argenteus juveniles were exposed to six concentrations of MS-222 (10, 25, 50, 75, 100, and 125 mg L-1); LED was established at 75 mg L-1. The juveniles were exposed to different deep anesthesia times (4, 7, 10, 12, and 15 min) at 75 mg L-1; the longest safe deep anesthesia time under LED was 10 min. Finally, the juveniles were randomly divided into four groups: control group (CG), draining group (DG, drain), anesthetic group (AG, drain + MS-222 + aquaculture treatment); and non-anesthetic group (NAG, drain + aquaculture treatment). Plasma cortisol levels in the NAG, AG, DG, and CG groups were 38.739 ± 1.065 (highest), 25.083 ± 0.587, 28.644 ± 0.612, and 22.620 ± 0.836 ng mL-1 (lowest). The AG group showed significant differences in superoxide dismutase, catalase, and malondialdehyde activities, except for glutathione. HSP70, HSP90, GR1, and GR2 mRNA levels in the NAG group increased sharply in response to stressors. GR1 and GR2 mRNA levels in the AG group also increased significantly, whereas HSP70 and HSP90 mRNA levels showed no significant differences. Thus, MS-222 can reduce oxidative damage, stress reaction, and resistance to aquaculture treatment stresses in P. argenteus.
Longitudinal Surveys Show that Urethral Catheters Harbor Recurrent Polymicrobial Biofilms with Cooperative and Competitive Behaviors Among Cohabitating Pathogens
Authors: Yu Yanbao , Singh Harinder , Tsitrin Tamara , Bekele Shiferaw , Moncera Kelvin J. , Sikorski Patricia , Torralba Manolito G. , Morrow Lisa , Wolcott Randall , Nelson Karen E. , Pieper Rembert 
Published: August 2018

AbstractThe analysis of catheter biofilms (CBs) from patients with neurogenic bladder disorders revealed persistent colonization by polymicrobial communities. The recurrence of bacterial species in the CBs of sequentially replaced catheters suggests urothelial reservoirs responsible for recolonization of the catheter surface. Proteomic data for CB samples were indicative of chronic inflammation in the patients’ urinary tracts via neutrophil and eosinophil infiltration and epithelial cell exfoliation. These host defense pathways, effective in killing pathogens during uncomplicated urinary tract infection, failed to eliminate CBs. Intermittent antibiotic drug treatment had different outcomes: either replacement of drug-susceptible by drug-tolerant bacteria or transient microbial biomass reduction followed by resurgence of the previously colonizing bacteria. Proteins that sequester iron and zinc such as lactotransferrin, lipocalin-2 and calprotectin were abundant in the patient’s CBs and urine sediments. Indicative of a host-pathogen battle for bivalent metal ions, acquisition and transport systems for such ions were highly expressed by many organisms residing in CBs. Species part of the Enterococcaceae and Aerococcaceae families, generally not well-characterized in their ability to synthesize siderophores, frequently cohabitated biofilms dominated by siderophore-producingEnterobacteriaceae.In support of metal acquisition cooperativity, we noticed positive abundance correlations for aProteus mirabilisyersiniabactin-type siderophore system and twoEnterococcus faecalisABC transporters. Distinct bacterial strains highly expressed known or putative cytotoxins that appeared to compromise the survival of co-resident bacteria, e.g. aP. mirabilishemolysin andPseudomonas aeruginosatype 6 secretion and pyoverdin biosynthesis systems. In conclusion, there is support for cooperative and competitive behaviors among bacteria cohabitating CBs.
HIV-Attributed Causes of Death in the Medical Ward at the Chris Hani Baragwanath Hospital, South Africa
Authors: Black Andrew , Sitas Freddy , Chibrawara Trust , Gill Zoe , Kubanje Mmamapudi , Williams Brian 
Published: August 2018

SummaryBackgroundThere are sparse data in Africa on the association between HIV infection and deaths from underlying medical conditions. Using records from the Chris Hani Baragwanath Hospital (CHBH) in Soweto, South Africa, we determined mortality from medical conditions associated with HIV.MethodsFrom January 2006 to December 2009 AB collected data on 15,725 deaths including age, sex, day of admittance and death, HIV status, ART initiation and CD4+ cell counts and reviewed the underlying cause of death using medical notes. Conditions known to be associated with HIV were cases; conditions not associated with HIV were controls. We calculate the HIV odds-ratios for cases relative to controls and HIV-attributable deaths as the fraction of those with each condition, the disease-attributable fraction (DA), and as the fraction of all deaths, the population-attributable fraction (PAF).InterpretationThe high prevalence of HIV among those that died in the medical wards at the CHBH, especially in those below the age of 50 years, demonstrates the impact of the HIV-epidemic on adult mortality and hospital services and the extent to which early antiretroviral treatment would have reduced the burden of both. Of the deaths included in the analysis the prevalence of HIV was 61% and the prevalence of AIDS related conditions was 69%. The HIV-attributable fraction was 36% in the whole sample and 60% in those that were HIV-positive. Cryptococcosis, Kaposi’s sarcoma and Pneumocystis jeroveci are highly predictive of HIV while TB, gastroenteritis and anaemia are very strongly associated with HIV. The greatest number of deaths attributable to HIV was among those dying of TB or of other respiratory conditions.FundingNo funding was received for this study.
MAP7 family proteins regulate kinesin-1 recruitment and activation
Authors: Hooikaas Peter Jan , Martin Maud , Mühlethaler Tobias , Kuijntjes Gert-Jan , Peeters Cathelijn A.E. , Katrukha Eugene A. , Ferrari Luca , Stucchi Riccardo , Verhagen Daan G.F. , Riel Wilhelmina E. van , Grigoriev Ilya , Altelaar A.F. Maarten , Hoogenraad Casper C. , Rüdiger Stefan G.D. , Steinmetz Michel O. , Kapitein Lukas C. , Akhmanova Anna 
Published: August 2018

AbstractKinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation of kinesin-1 by MAP7 proteins. We found that all four mammalian MAP7 family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1 and MAP7D3 act redundantly to enable kinesin-1-dependent transport and microtubule recruitment of the truncated kinesin-1 KIF5B-560, which contains the stalk but not the cargo-binding and autoregulatory regions. In vitro, purified MAP7 and MAP7D3 increase microtubule landing rate and processivity of kinesin-1 through transient association with the motor. MAP7 proteins promote binding of kinesin-1 to microtubules both directly, through the N-terminal microtubule-binding domain and unstructured linker region, and indirectly, through an allosteric effect exerted by the kinesin-binding C-terminal domain. Compared to MAP7, MAP7D3 has a higher affinity for kinesin-1 and a lower affinity for microtubules and, unlike MAP7, can be co-transported with the motor. We propose that MAP7 proteins are microtubule-tethered kinesin-1 activators, with which the motor transiently interacts as it moves along microtubules.SummaryA combination of experiments in cells and in vitro reconstitution assays demonstrated that mammalian MAP7 family proteins act redundantly to activate kinesin-1 and promote its microtubule binding and processivity by transiently associating with the stalk region of the motor.
Stimulus-induced Gamma Power Predicts the Amplitude of the Subsequent Visual Evoked Response
Authors: van Es Mats W.J. , Schoffelen Jan-Mathijs 
Published: August 2018

AbstractThe efficiency of neuronal information transfer in activated brain networks may affect behavioral performance. Gamma-band synchronization has been proposed to be a mechanism that facilitates neuronal processing of behaviorally relevant stimuli. In line with this, it has been shown that strong gamma-band activity in visual cortical areas leads to faster responses to a visual go cue. We investigated whether there are directly observable consequences of trial-by-trial fluctuations in non-invasively observed gamma-band activity on the neuronal response. Specifically, we hypothesizedthat the amplitude of the visual evoked response to a go cue can be predicted by gamma power in the visual system, in the window preceding the evoked response. Thirty-three human subjects (22 female) performed a visual speeded response task while their magnetoencephalogram (MEG) was recorded. The participants had to respond to a pattern reversal of a concentric moving grating. We estimated single trial stimulus-induced visual cortical gamma power, and correlated this with the estimated single trial amplitude of the most prominent event-related field (ERF) peak within the first 100 ms after the pattern reversal. In parieto-occipital cortical areas, the amplitude of the ERF correlated positively with gamma power, and correlated negatively with reaction times. No effects were observed for the alpha and beta frequency bands, despite clear stimulus onset induced modulation at those frequencies. These results support a mechanistic model, in which gamma-band synchronization enhances the neuronal gain to relevant visual input, thus leading to more efficient downstream processing and to faster responses.Significance statementGamma-band activity has been associated with many cognitive functions and improved behavioral performance. For example, high amplitude gamma-band activity in visual cortical areas before a go cue leads to faster reaction times. However, it remains unclear through which neural mechanism(s) gamma-band activity eventually affects behavior. We tested whether the strength of induced gamma-band activity affects evoked activity elicited by a subsequent visual stimulus. We found enhanced amplitudes of early visual evoked activity, and faster responses with higher gamma power. This suggests that gamma-band activity affects the neuronal gain to new sensory input, and thus these results bridge the gap between gamma power and behavior, and support the putative role of gamma-band activity in the efficiency of cortical processing.