bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Dimensional Activity in Spiking Neuronal Networks
Authors: Wärnberg Emil , Kumar Arvind 
Published: July 2018

AbstractSeveral recent studies have shown that neural activityin vivotends to be constrained to a low-dimensional manifold. Such activity does not arise in simulated neural networks with homogeneous connectivity and it has been suggested that it is indicative of some other connectivity pattern in neuronal networks. Surprisingly, the structure of the intrinsic manifold of the network activity puts constraints on learning. For instance, animals find it difficult to perform tasks that may require a change in the intrinsic manifold. Here, we demonstrate that theNeural Engineering Framework(NEF) can be adapted to design a biologically plausible spiking neuronal network that exhibit low dimensional activity. Consistent with experimental observations, the resulting synaptic weight distribution is heavy-tailed (log-normal). In our model, a change in the intrinsic manifold of the network activity requires rewiring of the whole network, which may be either not possible or a very slow process. This observation provides an explanation of why learning is easier when it does not require the neural activity to leave its intrinsic manifold.Significance statementA network in the brain consists of thousands of neurons. A priori, we expect that the network will have as many degrees of freedom as its number of neurons. Surprisingly, experimental evidence suggests that local brain activity is confined to a space spanned by 10 variables. Here, we describe an approach to construct spiking neuronal networks that exhibit low-dimensional activity and address the question: how the intrinsic dimensionality of the network activity restricts the learning as suggested by recent experiments? Specifically, we show that tasks that requires animals to change the network activity outside the intrinsic space would entail large changes in the neuronal connectivity, and therefore, animals are either slow or not able to acquire such tasks.
Atomic force microscopy reveals new biomarkers for monitoring subcellular changes in oxidative injury: neuroprotective effects of quercetin at the nanoscale
Authors: Jembrek Maja Jazvinšćak , Vlainić Josipa , Čadež Vida , Šegota Suzana 
Published: July 2018

AbstractOxidative stress is a process involved in the pathogenesis of many diseases, including atherosclerosis, hypertension, diabetes, Alzheimer’s disease etc. The biomarkers for assessing the degree of oxidative stress have been attracting much interest because of their potential clinical relevance in understanding cellular effects of free radicals and evaluation of the efficacy of drug treatment. Here, an interdisciplinary approach using atomic force microscopy (AFM) and cellular and biological molecular methods were used to obtain new potential biomarkers for monitoring oxidative stress condition. Biological methods confirmed the oxidative damage of investigated P19 neurons and revealed the underlying mechanism of quercetin protective action. AFM was employed to evaluate morphological (roughness) and nanomechanical (elasticity) properties that may be specific biomarkers for oxidative stress-induced cytoskeletal reorganization manifested by changes in the lateral dimension and height of neuronal somas. The morphological and nanomechanical analysis of neurons showed the strong mutual correlation between changes in cell membrane elasticity and neuroprotective effects of quercetin. Our findings indicate that AFM is a highly valuable tool for biomedical applications, detection and clarifying of drug-induced changes at the nanoscale and emphasize the potential of AFM approach in the development of novel therapeutic strategies directed against oxidative stress-induced neurodegeneration.
IL-2 Modulates Th2 cell Responses to Glucocorticoid: A Cause of Persistent Type 2 Inflammation?
Authors: Kanagalingam Tharsan , Vijeyakumaran Meerah , Palikhe Nami Shrestha , Solomon Lauren , Vliagoftis Harissios , Cameron Lisa 
Published: July 2018

ABSTRACTBackgroundInhaled glucocorticosteroids (GCs) are the main treatment for asthma as they reduce type 2 cytokine (IL-4, IL-5 and IL-13) expression and induce apoptosis. Asthma severity is associated with GC insensitivity, increased type 2 inflammation and circulating Th2 cells. Since IL-2 is a T cell survival factor, we assessed whether IL-2 levels associate with the proportion of Th2 cells and/or correlate with clinical features of asthma severity.MethodsPeripheral blood from asthma patients (n=18) was obtained and Th2 cell numbers determined by flow cytometry. Peripheral blood cells were activated with mitogen (24hrs) and supernatant levels of IL-2 and IL-13 measured by ELISA.In vitrodifferentiated Th2 cells were treated with dexamethasone and IL-2 and assessed for apoptosis by flow cytometry staining of Annexin V. Level of mRNA for anti-apoptotic (BCL-2) and pro-apoptotic (BIM) genes as well as IL-13 were determined by qRT-PCR.ResultsIL-2 produced by activated peripheral blood cells correlated negatively with lung function (FEV1) and positively with daily dose of inhaled GC. When patients were stratified based on IL-2 level, high IL-2 producers made more IL-13 and had more circulating Th2 cells.In vitro, increasing the level of IL-2 in the culture media was associated with resistance to DEX-induced apoptosis, more BCL-2 and less BIM mRNA. Th2 cells cultured with higher IL-2 also had more IL-13 mRNA and required higher concentrations of DEX for cytokine suppression.Conclusions and Clinical RelevanceIL-2 modulates Th2 cell responses to GC, supporting both their survival and pro-inflammatory capacity, suggesting that a patient’s potential to produce IL-2 may be a determinant in asthma severity.
Impaired miRNA processing by DICER1 downregulation endows thyroid cancer with increased aggressiveness
Authors: Ramírez-Moya Julia , Wert-Lamas León , Riesco-Eizaguirre Garcilaso , Santisteban Pilar 
Published: July 2018

AbstractThe global downregulation of miRNAs (miRs) is emerging as a common hallmark of cancer. However, the mechanisms underlying this phenomenon are not well known. We identified that the oncogenic miR-146b-5p attenuates miRNA biosynthesis by targeting DICER1 and reducing its expression. DICER1 overexpression inhibited all the miR-146b-induced aggressive phenotypes in thyroid cells. Systemic injection of an antimiR-146b in mice with orthotopic thyroid tumors suppressed tumor growth and recovered DICER1 levels. Notably, DICER1 downregulation promoted proliferation, migration, invasion and epithelial-mesenchymal transition through miR downregulation. Our analysis of TCGA revealed a general decrease in DICER1 expression in thyroid cancer that was associated with a worse clinical outcome. Administration of the small molecule enoxacin to promote DICER1 complex activity reduced tumor aggressiveness bothin vitroandin vivo. Overall, our data establish DICER1 as a tumor suppressor and that the oncogenic miR-146b contributes to its downregulation. Moreover, this study highlights a potential therapeutic application of RNA-based therapies including miR-inhibitors and restoration of the biogenesis machinery, which may provide treatments in for thyroid and other cancers.
Increased GITRL impairs the function of MDSCs and exacerbates primary Sjögren’s syndrome
Authors: Tian Jie , Rui Ke , Hong Yue , Lin Xiang , Wang Xiaohui , Xiao Fan , Xu Huaxi , Lu Liwei , Wang Shengjun 
Published: July 2018

AbstractIt is largely unclear how MDSCs contribute to the development of primary Sjögren’s syndrome (pSS). In experimental SS (ESS) mice, MDSCs were significantly increased but exhibited gradually diminished suppressive capacity during the disease progression. The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased with the development of pSS, and the increased GITRL was found to down-regulate the function of MDSCs while blocking GITR signal in MDSCs significantly restored their function and ameliorated ESS progression in mice. In pSS patients, expanded MDSCs expressed lower level of arginase were observed in patients with higher SSDAI. Moreover, the increased GITRL in serum was also found to closely correlate with the aberrant function of MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive capacity of MDSCs in pSS, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.
Psychoactive plant- and mushroom-associated alkaloids from two behavior modifying cicada pathogens
Authors: Boyce Greg R. , Gluck-Thaler Emile , Slot Jason C. , Stajich Jason E. , Davis William J. , James Tim Y. , Cooley John R. , Panaccione Daniel G. , Eilenberg Jørgen , Licht Henrik H. De Fine , Macias Angie M. , Berger Matthew C. , Wickert Kristen L. , Stauder Cameron M. , Spahr Ellie J. , Maust Matthew D. , Metheny Amy M. , Simon Chris , Kritsky Gene , Hodge Kathie T. , Humber Richard A. , Gullion Terry , Short Dylan P. G. , Kijimoto Teiya , Mozgai Dan , Arguedas Nidia , Kasson Matt T. 
Published: July 2018

AbstractEntomopathogenic fungi routinely kill their hosts before releasing infectious spores, but select species keep insects alive while sporulating, which enhances dispersal. Transcriptomics and metabolomics studies of entomopathogens with post-mortem dissemination from their parasitized hosts have unraveled infection processes and host responses, yet mechanisms underlying active spore transmission by Entomophthoralean fungi in living insects remain elusive. Here we report the discovery, through metabolomics, of the plant-associated amphetamine, cathinone, in four Massospora cicadina-infected periodical cicada populations, and the mushroom-associated tryptamine, psilocybin, in annual cicadas infected with Massospora platypediae or Massospora levispora, which appear to represent a single fungal species. The absence of some fungal enzymes necessary for cathinone and psilocybin biosynthesis along with the inability to detect intermediate metabolites or gene orthologs are consistent with possibly novel biosynthesis pathways in Massospora. The neurogenic activities of these compounds suggest the extended phenotype of Massospora that modifies cicada behavior to maximize dissemination is chemically-induced.
A screen for gene regulators encoded by Kaposi’s sarcoma-associated herpesvirus uncovers a novel role for the ORF42 protein in regulating the production of cellular and viral proteins
Authors: Butnaru Matthew , Rivas Hembly , Gaglia Marta M. 
Published: July 2018

AbstractThe tight control of viral and host gene expression is critical to the replication of herpesviruses, including the gamma-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). While some of the KSHV proteins that contribute to viral and host gene regulation are known, it is clear that there are additional uncharacterized contributing viral factors. Identifying these proteins and their role in gene regulation is important to determine the mechanistic underpinnings of the complex replication cycle of KSHV. Through a reporter-based screen, we have identified several new potential KSHV-encoded gene regulators, including the previously uncharacterized protein ORF42, which we find stimulates global protein production upon overexpression. We have generated an ORF42-null virus, which revealed that ORF42 is required for wild-type levels of virus production. Moreover, global protein synthesis and the accumulation of viral proteins are reduced in infected cells in the absence of ORF42, suggesting that ORF42 regulates protein synthesis during infection. A comparison of the effects of ORF42 on the levels of RNA and protein suggests that ORF42 acts post-transcriptionally to control protein levels. In addition to gene regulation, ORF42 may have other functions in virion formation, as it is found in viral particles, which is consistent with the described roles of the ORF42 homologs in alpha- and beta-herpesviruses.ImportanceKaposi’s sarcoma-associated herpesvirus (KSHV) causes Kaposi’s sarcoma, an AIDS-associated malignancy that remains one of the leading causes of cancer deaths in sub-Saharan Africa. Replication of the virus is important for tumor formation and inhibition of viral replication may be used for treatment. The correct levels and temporal expression of viral and host genes during KSHV replication are key to viral replication, but the mechanisms that control this regulation remain enigmatic. Here we identify several new KSHV proteins involved in viral and cellular gene regulation and characterize the previously unstudied KSHV ORF42 protein in regulation of viral and host protein levels and efficient formation of viral progeny.
Conjugation dynamics of self-transmissible and mobilisable plasmids intoE. coliO157:H7 onArabidopsis thalianarosettes
Authors: Remus-Emsermann Mitja N.P. , Pelludat Cosima , Gisler Pascal , Drissner David 
Published: July 2018

AbstractMany antibiotic resistance genes present in human pathogenic bacteria are believed to originate from environmental bacteria and conjugation of antibiotic resistance conferring plasmids is considered to be one of the major reasons for the increasing prevalence of antibiotic resistances. A hotspot for plasmid-based horizontal gene transfer is the phyllosphere,i.e.the surfaces of aboveground plant parts. Bacteria in the phyllosphere might serve as intermediate hosts with transfer capability to human pathogenic bacteria. In this study, the exchange of mobilisable and self-transmissible plasmids via conjugation was evaluated. The conjugation from the laboratory strainE. coliS17-1, the model phyllosphere colonizerPantoea eucalypti299R, and the model pathogenE. coliO157:H7∆stxto the recipient strainE. coliO157:H7∷MRE1O3∆stxin the phyllosphere ofArabidopsis thalianawas determined. The results suggest that short-term occurrence of a competent donor is sufficient to fix plasmids in a recipient population ofE. coliO157:H7∷MRE1O3∆stx. The spread of self-transmissible plasmids was limited after initial steep increases of transconjugants that contributed up to 10% of the total recipient population. The here-presented data of plasmid transfer will be important for future modelling approaches to estimate environmental spread of antibiotic resistance in agricultural production environments.ImportanceThis study investigated the transfer of antibiotic resistance conferring plasmids to enteropathogenicE. colion plant leaf surfaces. The results indicate that plasmid transfer may be high within the first 24 hours after inoculation. Transconjugant populations are maintained and stable for a considerable time frame on plant leaves, but invasion of the plasmid to the recipient population is limited.
A method for genome editing in the anaerobic magnetotactic bacteriumDesulfovibrio magneticusRS-1
Authors: Grant Carly R. , Rahn-Lee Lilah , LeGault Kristen N. , Komeili Arash 
Published: July 2018

ABSTRACTMagnetosomes are complex bacterial organelles that serve as model systems for studying cell biology, biomineralization, and global iron cycling. Magnetosome biogenesis is primarily studied in two closely related AlphaproteobacterialMagnetospirillumspp. that form cubooctahedral-shaped magnetite crystals within a lipid membrane. However, chemically and structurally distinct magnetic particles have also been found in physiologically and phylogenetically diverse bacteria. Due to a lack of molecular genetic tools, the mechanistic diversity of magnetosome formation remains poorly understood.Desulfovibrio magneticusRS-1 is an anaerobic sulfate-reducing Deltaproteobacterium that forms bullet-shaped magnetite crystals. A recent forward genetic screen identified ten genes in the conserved magnetosome gene island ofD. magneticusthat are essential for its magnetic phenotype. However, this screen likely missed many interesting mutants with defects in crystal size, shape, and arrangement. Reverse genetics to target the remaining putative magnetosome genes using standard genetic methods of suicide vector integration has not been feasible due to low transconjugation efficiency. Here, we present a reverse genetic method for targeted mutagenesis inD. magneticususing a replicative plasmid. To test this method, we generated a mutant resistant to 5-fluorouracil by making a markerless deletion of theuppgene that encodes uracil phosphoribosyltransferase. We also used this method for targeted marker exchange mutagenesis by replacingkupM,a gene identified in our previous screen as a magnetosome formation factor, with a streptomycin resistance cassette. Overall, our results show that targeted mutagenesis using a replicative plasmid is effective inD. magneticusand may also be applied to other genetically recalcitrant bacteria.IMPORTANCEMagnetotactic bacteria (MTB) are a group of organisms that form small, intracellular magnetic crystals though a complex process involving lipid and protein scaffolds. These magnetic crystals and their lipid membrane, termed magnetosomes, are model systems for studying bacterial cell biology and biomineralization as well as potential platforms for biotechnological applications. Due to a lack of genetic tools and unculturable representatives, the mechanisms of magnetosome formation in phylogenetically deeply-branching MTB remain unknown. These MTB contain elongated bullet-/tooth-shaped magnetite and greigite crystals that likely form in a manner distinct from the cubooctahedral-shaped magnetite crystals of the genetically tractable Alphaproteobacteria MTB. Here, we present a method for genome editing in the anaerobic DeltaproteobacteriumDesulfovibrio magneticusRS-1, the first cultured representative of the deeply-branching MTB. This marks a crucial step in developingD. magneticusas a model for studying diverse mechanisms of magnetic particle formation by MTB.
Point of care influenza testing using Alere-i Influenza A & B assay: a practical assessment
Authors: Blackmore Timothy K , Taylor James , Kelly Matthew , Buckley Jessica , Corban Karen , Tan Chor-Ee , Balm Michelle 
Published: July 2018

AbstractWe assessed the utility of the Alere i Influenza A & B point of care influenza test (Ai-POCIT) with laboratory testing using RT-PCR. 270 adult hospital patients had both Ai-POCIT and laboratory influenza tests conducted on the same sample. Overall, 30% and 32% influenza tests were positive by Ai-POCIT and RT-PCR, respectively. The sensitivity of the Ai-POCIT for influenza A, influenza B and any influenza were 93%, 100%, and 95%, respectively. Specificity was 100% for both viruses, but an 11% test failure rate indicates the need for better training of users. We believe that the use of nasopharyngeal (NP) swabs resulted in the observed high performance of the Ai-POCIT in comparison to other published studies. Ai-POCIT was regarded as very useful by front line clinical staff for clinical decision making and acute bed management.
AKT regulates mitotic progression of mammalian cells by phosphorylating MASTL
Authors: Reshi Irfana , Nisa Misbah Un , Farooq Umer , Gillani Syed Qaaifah , Bhat Sameer Ahmad , Sarwar Zarka , Fazili Khalid Majid , Andrabi Shaida 
Published: July 2018

AbstractMicrotubule associated serine threonine like kinase (MASTL) has been recently identified as an important regulator of mitosis. By inhibiting protein phosphatase 2A, it plays a crucial role in activating one of the most important mitotic kinases known as cyclin dependent kinase1 (CDK1). MASTL has been seen to be up regulated in various types of cancers and is involved in tumor recurrence. It is activated by CDK1 through its auto regulatory loop but the complete mechanism of its activation is still unclear. In this study, we evaluated the regulation of MASTL via AKT during mitosis. Here we report that AKT phosphorylates MASTL at T299 which plays a critical role in its activation. Our results suggest that AKT increases CDK1 mediated phosphorylation and hence activity of MASTL which in turn promotes cell proliferation.. We also show that the oncogenic potential of AKT is augmented by MASTL activation as the AKT mediated oncogenesis in colorectal cell lines can be attenuated by inhibiting and/or silencing MASTL. In brief, we report that AKT has an important role in the progression of mitosis in mammalian cells and it does so through the phosphorylation and activation of MASTL.
Polygenic predictors of age-related decline in cognitive ability
Authors: Ritchie Stuart J. , Hill W. David , Marioni Riccardo E. , Davies Gail , Hagenaars Saskia P. , Harris Sarah E. , Cox Simon R. , Taylor Adele M. , Corley Janie , Pattie Alison , Redmond Paul , Starr John M. , Deary Ian J. 
Published: July 2018

AbstractPolygenic scores can be used to distil the knowledge gained in genome-wide association studies for prediction of health, lifestyle, and environmental factors in independent samples. In this preregistered study, we used fourteen polygenic scores to predict variation in cognitive ability level at age 70 and cognitive change from age 70 to age 79 in the longitudinal Lothian Birth Cohort 1936 study. The polygenic scores were created for phenotypes that have been suggested as risk or protective factors for cognitive ageing. Cognitive abilities within old age were indexed using a latent general factor estimated from thirteen varied cognitive tests taken at four waves, each three years apart (initialn= 1,091 age 70; finaln= 550 age 79). The general factor indexed over two-thirds of the variance in longitudinal cognitive change. We also ran an additional analysis using an age-11 intelligence test to index cognitive change from age 11 to age 70. Several polygenic scores were associated with the level of cognitive ability at age-70 baseline (range of standardizedβ-values = –178 to .264), and the score for education was associated with cognitive change from childhood to age 70 (standardized = .102). None was statistically significantly associated with variation in cognitive change between ages 70 and 79.APOEe4 status made a significant prediction of cognitive decline from age 70 to 79 (standardizedβ= –319 for carriers vs. non-carriers). The results suggest that the predictive validity for cognitive ageing of polygenic scores derived from genome-wide association study summary statistics is not yet on a par withAPOEe4, a more well-established predictor.
Dengue virus infection changesAedes aegyptioviposition olfactory preferences
Authors: Gaburro Julie , Paradkar Prasad N , Klein Melissa , Bhatti Asim , Nahavandi Saeid , Duchemin Jean-Bernard 
Published: July 2018

AbstractAedes aegyptimosquitoes, main vectors for numerous flaviviruses, have olfactory preferences and are capable of olfactory learning especially when seeking their required environmental conditions to lay their eggs. In this study, we showed that semiochemical conditions duringAedes aegyptilarval rearing affected future female choice for oviposition: water-reared mosquitoes preferred to lay eggs in water or p-cresol containers, while skatole reared mosquitoes preferred skatole sites. Using two independent behavioural assays, we showed that this skatole preference was lost in mosquitoes infected with dengue virus. Viral RNA was extracted from infected female mosquito heads, and an increase of virus load was detected from 3 to 10 days post infection, indicating replication in the insect head and possibly in the central nervous system. Expression of selected genes, potentially implied in olfactory learning processes, were also altered during dengue infection. Based on these results, we hypothesise that dengue virus infection alters gene expression in the mosquito’s head and is associated with a loss of olfactory preferences, possibly modifying oviposition site choice of female mosquitoes.