bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant uses in a traditional fisherman community in northeastern Brazil
Authors: Tng DYP , Apgaua DMG , Lisboa MDS , El-Hani CN 
Published: April 2019

AbstractBackgroundKnowledge of traditional plant use in rural communities is under threat from urbanization and also land use change. Hence, elucidating region-specific patterns traditional knowledge of habitat resource use is crucial for assisting policy making with regard to nature conservation, human nutrition, and human health. Using original data from northeast Bahia, Brazil, we aim to document the collective knowledge of plant use possessed by artisanal fishermen and women in fishing communities, related to medicinal, construction, technology and ritualistic/religious uses.MethodsData were collected through interviews with and opportunistic guided tours by local specialists to record the local knowledge of plant use and methods of use.ResultsThrough interviews, 116 species of plants from 104 genera and 47 botanical families were identified along with their local names, plant parts utilized, habitats, and preparation methods, and an additional 26 spp. for which only local names were available. Of these, 72 spp. are used as medicine, 48 spp. as non-conventional edibles, 31 spp. for construction and 11 for religious/mystical purposes. Female informants generally cited more food and medicinal plants than male informants. All interviewees unanimously expressed that the use of plants for medicines and fishing technology has significantly reduced or been superseded by modern materials.ConclusionThe present study demonstrates that the rich collective plant use knowledge of an artisanal fishing community in northeast Brazil. The results of this study serves as a framework for to extend ethnobotanical investigations to other traditional fishing communities in the vicinity, and also to examine more social and demographic factors influencing traditional knowledge related to uses of plants. Finally, the rich tradition of plant use in the region underpins the need to encourage measures to preserve this cultural knowledge and conserve the natural environments that are a source of these plants.
A putative enoyl-CoA hydratase contributes to biofilm formation and the antibiotic tolerance ofAchromobacter xylosoxidans
Authors: Cameron Lydia C. , Bonis Benjamin , Phan Chi Q. , Kent Leslie A. , Lee Alysha K. , Hunter Ryan C. 
Published: April 2019

ABSTRACTAchromobacter xylosoxidanshas attracted increasing attention as an emerging pathogen in patients with cystic fibrosis. Intrinsic resistance to several classes of antimicrobials and the ability to form robust biofilmsin vivocontribute to the clinical manifestations of persistentA. xylosoxidansinfection. Still, much ofA. xylosoxidansbiofilm formation remains uncharacterized due to the scarcity of existing genetic tools. Here we demonstrate a promising genetic system for use inA. xylosoxidans; generating a transposon mutant library which was then used to identify genes involved in biofilm developmentin vitro. We further described the effects of one of the genes found in the mutagenesis screen, encoding a putative enoyl-CoA hydratase, on biofilm structure and tolerance to antimicrobials. Through additional analysis, we find that a cis-2 fatty acid signaling compound is essential toA. xylosoxidansbiofilm ultrastructure and maintenance. This work describes methods for the genetic manipulation ofA. xylosoxidansand demonstrated their use to improve our understanding ofA. xylosoxidanspathophysiology.
Isoform specificity of PKMs during long-term facilitation in Aplysia is mediated through stabilization by KIBRA
Authors: Ferguson Larissa , Hu Jiangyuan , Cai Diancai , Chen Shanping , Dunn Tyler W , Glanzman David L , Schacher Samuel , Sossin Wayne S. 
Published: April 2019

AbstractPersistent activity of protein kinase M (PKM), the truncated form of protein kinase C (PKC), can maintain long-term changes in synaptic strength in many systems including the hermaphrodite marine mollusk, Aplysia californica. Moreover, different types of long-term facilitation (LTF) in cultured Aplysia sensorimotor synapses rely on the activities of different PKM isoforms in the presynaptic sensory neuron and postsynaptic motor neuron. When the atypical PKM isoform was required, the kidney and brain expressed adaptor protein (KIBRA) was also required. Here, we explore how this isoform specificity is established. We find that PKM overexpression in the motor neuron, but not the sensory neuron, is sufficient to increase synaptic strength and that this activity is not isoform specific. KIBRA is not the rate-limiting step in facilitation since overexpression of KIBRA is neither sufficient to increase synaptic strength, nor to prolong a form of PKM-dependent intermediate synaptic facilitation. However, the isoform specificity of dominant negative (DN)-PKMs to erase LTF is correlated with isoform specific competition for stabilization by KIBRA. We identify a new conserved region of KIBRA. Different splice isoforms in this region stabilize different PKMs based on the isoform-specific sequence of an alpha-helix ‘handle’ in the PKMs. Thus, specific stabilization of distinct PKMs by different isoforms of KIBRA can explain the isoform specificity of PKMs during LTF in Aplysia.Significance StatementLong lasting changes in synaptic plasticity associated with memory formation are maintained by persistent protein kinases. We have previously shown in the Aplysia sensorimotor model that distinct isoforms of persistently active protein kinase Cs (PKMs) maintain distinct forms of long-lasting synaptic changes, even when both forms are expressed in the same motor neuron. Here, we show that, while the effects of overexpression of PKMs in not isoform specific, isoform specificity is defined by a ‘handle’ helix in PKMs that confers stabilization by distinct splice forms in a previously undefined domain of the adaptor protein KIBRA. Thus, we define new regions in both KIBRA and PKMs that define the isoform specificity for maintaining synaptic strength in distinct facilitation paradigms.
Hindbrain V2a neurons impose rhythmic activity on motor neurons in anin vitroreticulospinal circuit
Authors: Bubnys Adele V , Kandel Hagar , Kow Lee-Ming , Pfaff Donald W , Tabansky Inna 
Published: April 2019

AbstractThe reticulospinal system is an evolutionarily conserved pathway among vertebrates that relays locomotor control signals from the hindbrain to the spinal cord. Recent studies have identified specific hindbrain cell types that participate in this circuit, including Chx10+neurons of the medullary reticular formation, which project to the spinal cord and are active during periods of locomotion. To create a system in which reticulospinal neurons communicate with spinal motor effectors, we have constructed anin vitromodel using two purified excitatory neuronal subtypes: HB9+spinal motor neurons and Chx10+hindbrain neurons. Cultured separately, these neurons exhibit cell type-specific patterns of activity; the Chx10+cultures developed regular, synchronized bursts of activity that recruited neurons across the entire culture, whereas motor neuron activity consisted of an irregular pattern. A combination of the two subtypes produced cultures in which Chx10+neurons recruited the motor neurons into synchronized network bursts, which were dependent on AMPA receptors. In addition to demonstrating that the activity ofin vitronetworks can depend on the developmental identity of their constituent neurons, we provide a new model with genetically specified nerve cell types to study the activity of a reticulospinal circuit.Significance statementModels of the brain that use cultured neurons are usually comprised of a complex mixture of different kinds of cells, making it hard to determine how each cell type contributes to the overall pattern of activity. We made a simplified culture containing two cell types known to form a reticulospinal circuitin vivo. While in isolated cultures, each cell type had a distinct pattern of activity, in coculture the activity of one cell type came to dominate, indicating that the patterns observed in complex neuronal cultures arise in part from the distinctive properties of the constituent neurons.
Population structure and pangenome analysis of Enterobacter bugandensis uncover the presence ofblaCTX-M-55,blaNDM-5andblaIMI-1, along with sophisticated iron acquisition strategies
Authors: Matteoli Filipe P. , Passarelli-Araujo Hemanoel , Pedrosa-Silva Francisnei , Olivares Fabio L. , Venancio Thiago M. 
Published: April 2019

ABSTRACTEnterobacter bugandensisis a recently described species that has been largely associated with nosocomial infections. Here, we report the genome of a non-clinicalE. bugandensisstrain. We used this and other several publicly availableE. bugandensisgenomes to obtain the species pangenome, investigate the conservation of important genes, and elucidate general population structure features of the species. Core- and whole-genome multilocus sequence typing (cgMLST and wgMLST, respectively) allowed the detection of fiveE. bugandensisphylogroups (PG-A to E). We found important antimicrobial resistance and virulence determinants associated with specific PGs, notably PG-A and PG-E. IncFII was the most prevalent plasmid replicon type in this species. We uncovered several extended-spectrum β-lactamases, includingblaCTX-M-55andblaNDM-5, present in an IncX replicon type plasmid, described here for the first time inE. bugandensis. Genetic context analysis ofblaNDM-5revealed the resemblance of this plasmid with other IncX plasmids isolated from other bacteria from the same country. Further, three distinctive siderophore producing operons were found in theE. bugandensispangenome: enterobactin (ent), aerobactin (iuc/iut), and salmochelin (iro). The latter operon is conserved in all PG-E isolates. Collectively, our findings provide novel insights on the lifestyle, physiology, antimicrobial, and virulence profiles ofE. bugandensis.
Medial prefrontal cortex guides goal-directed decision-making about hunger and thirst
Authors: Eiselt Anne-Kathrin , Chen Jim , Arnold Jon , Kim Tahnbee , Sternson Scott M. 
Published: April 2019

AbstractDecision-making guided by self-evaluation of bodily need states (interoception) is thought to be important for cognitive control over eating or drinking1. However, interoception of body states is notoriously unreliable2–4 because hunger and thirst have similar motivational characteristics5. Consequently, individuals may inaccurately assess their need state and consume food when dehydrated, leading some healthcare professionals to advise overweight patients to drink water before eating6–8. Neuroimaging in humans9–11 and recordings in rodents12–15 indicate medial prefrontal frontal cortex (mPFC) involvement in need state-dependent decisions about hunger and thirst, but mPFC surgical lesions16,17 and electrical activity perturbations have little influence on eating or drinking18,19. To investigate need-state dependent decision-making as well as the function of mPFC in hunger and thirst, we developed an instrumental foraging task for mice that mimics key elements of human decisions. When homeostatic need state was variable, mice did not show intrinsic knowledge of hunger or thirst state but, instead, rapidly identified their need after consumption of small portions of food and water (outcome evaluation). We observed a food-seeking bias, even in thirsty mice, that required outcome evaluation for mice to correctly seek water. mPFC was required for need state-dependent decisions about hunger and thirst, specifically under variable need state conditions. Food-seeking or water-seeking choices were controlled by multiple decision-making processes, and mPFC was involved in goal-directed decisions about the identity of need states. Thus, we have discovered a role for mPFC in decision-making about hunger and thirst, which is relevant for human behaviors that contribute to obesity.
Possible origin of the scrapie genome in small endogenous RNAs; studies on eight candidate species in 263K scrapie-infected hamster brain
Authors: Barnard Eleanor , Estibeiro Kathryn , Duncan Rory , Baird Janet , Fettes David , Wood Jacqueline , Fraser Hugh , Estibeiro Peter , Lathe Richard 
Published: April 2019

SUMMARYThe identity of the etiologic agent of the transmissible spongiform encephalopathies (TSEs), including bovine spongiform encephalopathy (BSE), scrapie and Creutzfeldt-Jakob disease (CJD), remains unknown. While much attention has been given to the hypothesis that the TSEs may be caused by a proteinaceous infectious agent or ‘prion’, there is considerable evidence to suggest that this hypothesis is incomplete. We have pursued an alternative contention: that the etiologic agent comprises in part a modified and replicating form of an endogenous nucleic acid, probably RNA. The ‘endovirus’ hypothesis contends that the parental molecule is most likely to be a small and highly-structured cellular RNA that can convert to a replicating molecule by a finite number of nucleotide sequence changes. We have begun a systematic analysis of candidate molecular species present in hamster brain infected with scrapie strain 263K. Initial work focussed on the 7S group of small RNAs. Examination of 7-2, 7SK and 7SL failed to reveal differences in abundance and/or sequence between normal and scrapie (263K)-infected hamster brain. Inspection of other possible candidates, including U3, H1/8-2 and novel molecules KR1, nu1 and nu2, similarly failed to provide evidence for scrapie-specific molecular variants; alterations to the KR1 sequence failed to correlate with disease. We present sequences of hamster RNAs 7-2, 7SK, 7SL, H1/8-2, U3, nu1, nu2 and KR1. Together our data so far fail to contradict or confirm the hypothesis, while arguing that the major species of these 8 RNA molecules are unlikely to correspond to the etiologic agent of the TSEs.
Differential Expression of Mucins in Murine Olfactory Versus Respiratory Epithelium
Authors: Kennel Christopher , Gould Elizabeth A. , Larson Eric D. , Salcedo Ernesto , Vickery Thad W. , Restrepo Diego , Ramakrishnan Vijay R. 
Published: April 2019

AbstractMucins are a key component of the airway surface liquid and serve many functions. Given the numerous differences in olfactory versus respiratory nasal epithelia, we hypothesized that mucins would be differentially expressed between these two areas. Secondarily, we evaluated for changes in mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed in a mouse model to determine the expression of mucins 1, 2, 5AC and 5B in nasal respiratory and olfactory epithelia of control mice and one week after exposure to 8 gy of radiation. Mucins 1, 5AC and 5B exhibited differential expression between olfactory and respiratory epithelium while mucin 2 showed no difference. Within the olfactory epithelium, mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in respiratory epithelium it was only intermittently expressed. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the olfactory epithelium. Mucin 5B was expressed by submucosal glands in the olfactory epithelium but by surface epithelial cells in respiratory epithelium. At one-week after exposure to single-dose 8 gy of radiation, no qualitative effects were seen on mucin expression. Our findings demonstrate that murine olfactory and respiratory epithelia express mucins differently, and characteristic patterns of mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 gy) does not appear to affect mucin expression at one week.Author RolesChristopher Kennel conceived, organized and executed the study, performed the analysis, and contributed to the manuscript.Elizabeth Gould conceived and executed the study, and contributed to the manuscript.Diego Restrepo conceived and executed the study, supervised the experiments, reviewed the analysis, and contributed to the manuscript.Ernesto Salcedo performed experiments and reviewed the manuscript.Thad Vickery performed experiments and reviewed the manuscript.Eric Larson performed experiments and reviewed the manuscript.Vijay Ramakrishnan conceived and executed the study, reviewed the analysis, and contributed to the manuscript.All authors discussed the results and implications and contributed to the final manuscript.
Prognostic Analysis of Histopathological Images Using Pre-Trained Convolutional Neural Networks
Authors: Lu Liangqun , Daigle Bernie 
Published: April 2019

AbstractBackgroundHistopathological images contain rich phenotypic descriptions of the molecular processes underlying disease progression. Convolutional neural networks (CNNs), a state-of-the-art image analysis technique in computer vision, automatically learns representative features from such images which can be useful for disease diagnosis, prognosis, and subtyping. Despite hepatocellular carcinoma (HCC) being the sixth most common type of primary liver malignancy with a high mortality rate, little previous work has made use of CNN models to delineate the importance of histopathological images in diagnosis and clinical survival of HCC.ResultsWe applied three pre-trained CNN models – VGG 16, Inception V3, and ResNet 50 – to extract features from HCC histopathological images. The visualization and classification showed clear separation between cancer and normal samples using image features. In a univariate Cox regression analysis, 21.4% and 16% of image features on average were significantly associated with overall survival and disease-free survival, respectively. We also observed significant correlations between these features and integrated biological pathways derived from gene expression and copy number variation. Using an elastic net regularized CoxPH model of overall survival, we obtained a concordance index (C-index) of 0.789 and a significant log-rank test (p = 7.6E-18) after applying Inception image features. We also performed unsupervised classification to identify HCC subgroups from image features. The optimal two subgroups discovered using Inception image features were significantly associated with both overall (C-index = 0.628 and p = 7.39E-07) and disease-free survival (C-index =0.558 and p = 0.012). Our results suggest the feasibility of feature extraction using pre-trained models, as well as the utility of the resulting features to build an accurate prognosis model of HCC and highlight significant correlations with clinical survival and biological pathways.ConclusionsThe image features extracted from HCC histopathological images using the pre-trained CNN models VGG 16, Inception V3 and ResNet 50 can accurately distinguish normal and cancer samples. Furthermore, these image features are significantly correlated with relevant biological outcomes.
Immune Landscape of Invasive Ductal Carcinoma Tumour Microenvironment Identifies a Prognostic and Immunotherapeutically Relevant Gene Signature
Authors: Bao Xuanwen , Shi Run , Zhang Kai , Xin Shan , Li Xin , Zhao Yanbo , Wang Yanfang 
Published: April 2019

AbstractBackgroundInvasive ductal carcinoma (IDC) is a clinically and molecularly distinct disease. Tumour microenvironment (TME) immune phenotypes play crucial roles in predicting clinical outcomes and therapeutic efficacy.MethodIn this study, we depict the immune landscape of IDC by using transcriptome profiling and clinical characteristics retrieved from The Cancer Genome Atlas (TCGA) data portal. Immune cell infiltration was evaluated via single-sample gene set enrichment (ssGSEA) analysis and systematically correlated with genomic characteristics and clinicopathological features of IDC patients. Furthermore, an immune signature was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm. A random forest algorithm was applied to identify the most important somatic gene mutations associated with the constructed immune signature. A nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed by multivariate Cox regression.ResultsThe IDC were clustered into low immune infiltration, intermediate immune infiltration, and high immune infiltration by the immune landscape. The high infiltration group had a favourable survival probability compared with that of the low infiltration group. The low-risk score subtype identified by the immune signature was characterized by T cell-mediated immune activation. Additionally, activation of the interferon-α response, interferon-γ response and TNF-α signalling via the NFκB pathway was observed in the low-risk score subtype, which indicated T cell activation and may be responsible for significantly favourable outcomes in IDC patients. A random forest algorithm identified the most important somatic gene mutations associated with the constructed immune signature. Furthermore, a nomogram that integrated clinicopathological features with the immune signature to predict survival probability was constructed, revealing that the immune signature was an independent prognostic biomarker. Finally, the relationship of VEGFA, PD1, PDL-1 and CTLA-4 expression with the immune infiltration landscape and the immune signature was analysed to interpret the responses of IDC patients to immune checkpoint inhibitor therapy.ConclusionTaken together, we performed a comprehensive evaluation of the immune landscape of IDC and constructed an immune signature related to the immune landscape. This analysis of TME immune infiltration patterns has shed light on how IDC respond to immune checkpoint therapy and may guide the development of novel drug combination strategies.
A new approach to automated CBMN scoring following high doses
Authors: Repin Mikhail , Brenner David J. , Garty Guy 
Published: April 2019

AbstractIn recent years we have automated the CBMN assay using microvolumes of blood, processed in multiwell plates. We have seen that at doses above 6 Gy the detected yield of micronuclei actually declines with dose, likely because of mitotic delay, preventing cells from forming micronuclei and also, when using one color imaging, resulting in many false binucleated cells, consisting of two randomly-adjacent nuclei. By using the inverse mitotic index (the ratio of mononuclear to binuclear cells) to adjust the micronucleus yield we were able to obtain a monotonic increasing dose response curve at doses of up to at least 10 Gy from the same samples which generated dose-response curve with a peak near 6 Gy, when scored using the traditional micronucleus yield.
Structural basis for the differential regulatory roles of the PDZ domain in C-terminal processing proteases
Authors: Chueh Chuang-Kai , Som Nilanjan , Ke Lu-Chu , Ho Meng-Ru , Reddy Manjula , Chang Chung-I 
Published: April 2019

AbstractCarboxyl (C)-terminal processing proteases (CTPs) participate in protective and regulatory proteolysis in bacteria. The PDZ domain is central to the activity of CTPs but plays inherently different regulatory roles. For example, the PDZ domain inhibits the activity of the signaling protease CtpB by blocking the active site but is required for the activation of Prc (or Tsp), a tail-specific protease that degrades the ssrA-tagged proteins. Here, by structural and functional analysis we show that in the unliganded resting state of Prc, the PDZ domain is docked inside the bowl-shaped scaffold without contacting the active site, which is kept in a default misaligned conformation. In Prc, a hydrophobic substrate sensor distinct from CtpB engages substrate binding to the PDZ domain and triggers a structural remodeling to align the active site residues. Therefore, this work reveals the structural basis for understanding the contrasting roles of the PDZ domain in the regulation of CTPs.