bluuebunny/crossref_metadata_2025_split huggingface dataset:
Information Integration and Collective Motility in Phototactic Cyanobacteria
Authors: Menon S. N. , Varuni P. , Menon G I. 
Published: March 2019

AbstractCells in microbial colonies integrate information across multiple spatial and temporal scales while sensing environmental cues. A number of photosynthetic cyanobacteria respond in a directional manner to incident light, resulting in the phototaxis of individual cells. Colonies of such bacteria exhibit large-scale changes in morphology, arising from cell-cell interactions, during phototaxis. These interactions occur through type IV pili-mediated physical contacts between cells, as well as through the secretion of complex polysaccharides (‘slime’) that facilitates cell motion. Here, we describe a computational model for such collective behaviour in colonies of the cyanobacteriumSynechocystis. The model is designed to replicate observations from recent experiments on the emergent response of the colonies to varied light regimes. It predicts the complex colony morphologies that arise as a result. We ask if changes in colony morphology during phototaxis can be used to infer if cells integrate information from multiple light sources simultaneously, or respond to these light sources separately at each instant of time. We find that these two scenarios cannot be distinguished from the shapes of colonies alone. However, we show that tracking the trajectories of individual cyanobacteria provides a way of determining their mode of response. Our model allows us to address the emergent nature of this class of collective bacterial motion, linking individual cell response to the dynamics of colony shape.Statement of SignificanceMicrobial colonies in the wild often consist of large groups of heterogeneous cells that coordi-nate and integrate information across multiple spatio-temporal scales. We describe a computational model for one such collective behaviour, phototaxis, in colonies of the cyanobacteriumSynechocystisthat move in response to light. The model replicates experimental observations the response of cyanobacterial colonies to varied light regimes, and predicts the complex colony morphologies that arise as a result. The results suggest that tracking the trajectories of individual cyanobacteria may provide a way of determining their mode of information integration. Our model allows us to address the emergent nature of this class of collective bacterial motion, linking individual cell response to the large scale dynamics of the colony.
Time-resolved RNA-seq profiling of the infection of Dictyostelium discoideum by Mycobacterium marinum reveals an integrated host response to damage and stress
Authors: Hanna N. , Burdet F. , Melotti A. , Bosmani C. , Kicka S. , Hilbi H. , Cosson P. , Pagni M. , Soldati T. 
Published: March 2019

ABSTRACTTuberculosis remains the most pervasive infectious disease and the recent emergence of multiple drug-resistant strains emphasizes the need for more efficient drug treatments. The experimentally versatile Dictyostelium discoideum – Mycobacterium marinum infection model provides a powerful system to study mycobacteria pathogenicity and host response. In this study, a time-resolved transcriptomic analysis of the amoeba D. discoideum was performed to decipher the different host pathways impacted during infection. We investigated how D. discoideum fine-tunes its gene expression in response to M. marinum infection by assessing the transcriptomic profile covering the critical stages of entry, establishment of a permissive niche, proliferation and dissemination (1, 3, 6, 12, 24 and 48 hours post infection). Differential gene expression provided a fingerprint of the transcriptome of the host cell in the presence of mycobacteria, and helped identify specific markers and molecular signatures of infection. Enrichment pathway analysis showed that most of the Biological Processes (BP) of upregulated genes at early time point of infection hinted towards damage response and cellular defence, especially in specific pathways involved in membrane repair (ESCRT) and bacteria elimination (autophagy). Whereas at late time points of infection, BP related to starvation were upregulated. Some other signatures were more unexpected, such as cell cycle (downregulation of cytosolic large & small ribosomal subunits) and upregulation of metabolic adaptations (lipids transport).
The WT1-like transcription factor Klumpfuss maintains lineage commitment in the intestine
Authors: Korzelius Jerome , Ronnen-Oron Tal , Baldauf Maik , Meier Elke , Sousa-Victor Pedro , Jasper Heinrich 
Published: March 2019

AbstractStem cell (SC) lineages in barrier epithelia exhibit a high degree of plasticity. Mechanisms that govern the precise specification of SC daughter cells during regenerative episodes are therefore critical to maintain homeostasis. One such common mechanism is the transient activation of the Notch (N) signaling pathway. N controls the choice between absorptive and entero-endocrine cell fates in both the mammalian small intestine and theDrosophilamidgut, yet how precisely N signaling promotes lineage restriction in progenitor cells remains unclear. Here, we describe a role for the WT1-like transcription factor Klumpfuss (Klu) in restricting the fate ofDrosophilaenteroblasts (EBs) downstream of N activation. Klu is transiently induced in Notch-positive EBs and its transient activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) cell fates by repressing E(Spl)m8-HLH and Phyllopod, both negative regulators of the proneural gene Scute, which is essential for EE differentiation. At the same time, Klu suppresses cell cycle genes, committing EBs to differentiation. Klu-mediated repression of its own transcription further sets up a negative feedback loop that ensures temporal restriction of Klu-mediated gene regulation, and is essential for subsequent differentiation of ECs. Our findings define a transient cell state in which EC lineage restriction is cemented, and establish a hierarchy of transcriptional programs critical in executing a differentiation program downstream of initial induction events governed by N signaling.
Mammillothalamic disconnection alters hippocampo-cortical oscillatory activity and microstructure: Implications for diencephalic amnesia
Authors: Dillingham CM , Milczarek MM , Perry JC , Frost BE , Parker GD , Assaf Y , Sengpiel F , O’Mara SM , Vann SD 
Published: March 2019

AbstractDiencephalic amnesia can be as disruptive as the more commonly known temporal lobe amnesia, yet the precise contribution of diencephalic structures to memory processes remains elusive. We used discrete lesions of the mammillothalamic tract to model aspects of diencephalic amnesia and assessed the impact of these lesions on multiple measures of activity and plasticity within the hippocampus and retrosplenial cortex. Lesions of the mammillothalamic tract had widespread indirect effects on hippocampo-cortical oscillatory activity within both theta and gamma bands. Both within-region oscillatory activity and cross-regional synchrony were altered. The network changes were state-dependent, displaying different profiles during locomotion and paradoxical sleep. Consistent with the associations between oscillatory activity and plasticity, complementary analyses using several convergent approaches revealed microstructural changes, which appeared to reflect a suppression of learning-induced plasticity in lesioned animals. Together, these combined findings suggest a mechanism by which damage to the medial diencephalon can impact upon learning and memory processes, highlighting important role for the mammillary bodies in the co-ordination of hippocampo-cortical activity.
The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor
Authors: Coe Elizabeth A , Tan Jennifer Y , Shapiro Michael , Louphrasitthiphol Pakavarin , Bassett Andrew R , Marques Ana C , Goding Colin R , Vance Keith W 
Published: March 2019

ABSTRACTThe MITF and SOX10 transcription factors regulate the expression of genes important for melanoma proliferation, invasion and metastasis. Despite growing evidence of the contribution of long noncoding RNAs (lncRNAs) in cancer, including melanoma, their functions within MITF-SOX10 transcriptional programmes remain poorly investigated. Here we identified 245 candidate melanoma associated lncRNAs whose loci are co-occupied by MITF-SOX10 and that are enriched at active enhancer-like regions. We characterise the function and molecular mechanism of action of one of these lncRNAs,Disrupted In Renal Carcinoma 3(DIRC3), and show that it operates as a MITF-SOX10 regulated tumour suppressor.DIRC3depletion in human melanoma cells leads to increased anchorage-independent growth, a hallmark of malignant transformation, whilst melanoma patients classified by lowDIRC3expression have decreased survival.DIRC3is a nuclear lncRNA that functions locally to activate expression of its neighbouringIGFBP5tumour suppressor through modulating chromatin structure and suppressing SOX10 binding to putative regulatory elements within theDIRC3locus. In turn,DIRC3dependent regulation ofIGFBP5impacts the expression of genes involved in multiple cancer associated processes. Our work indicates that lncRNA components of the MITF-SOX10 networks are an important new class of melanoma regulators and candidate therapeutic targets.
A Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion
Authors: Cai Xiao-Chuan , Zhang Tuo , Kim Eui-jun , Jiang Ming , Wang Ke , Wang Junyi , Chen Shi , Zhang Nawei , Wu Hong , Li Fengling , dela Seña Carlo C. , Zheng Hong , Vivcharuk Victor , Niu Xiang , Zheng Weihong , Lee Jonghan P. , Chen Yuling , Barsyte Dalia , Szewczyk Magda , Hajian Taraneh , Ibáñez Glorymar , Dong Aiping , Dombrovsky Ludmila , Zhang Zhenyu , Deng Haiteng , Min Jinrong , Arrowsmith Cheryl H. , Mazutis Linas , Shi Lei , Vedadi Masoud , Brown Peter J. , Xiang Jenny , Qin Li-Xuan , Xu Wei , Luo Minkui 
Published: March 2019

AbstractCARM1 is a cancer-relevant protein arginine methyltransferase that regulates many aspects of transcription. Its pharmacological inhibition is a promising anti-cancer strategy. HereSKI-73is presented as a CARM1 chemical probe with pro-drug properties.SKI-73can rapidly penetrate cell membranes and then be processed into active inhibitors, which are retained intracellularly with 10-fold enrichment for days. These compounds were characterized for their potency, selectivity, modes of action, and on-target engagement.SKI-73recapitulates the effect of CARM1 knockout against breast cancer cell invasion. Single-cell RNA-seq analysis revealed that theSKI-73-associated reduction of invasiveness act via altering epigenetic plasticity and suppressing the invasion-prone subpopulation. Interestingly,SKI-73and CARM1 knockout alter the epigenetic plasticity with remarkable difference, arguing distinct modes of action between the small-molecule and genetic perturbation. We therefore discovered a CARM1-addiction mechanism of cancer metastasis and developed a chemical probe to target this process.
Ethanolic extract of Ocimum sanctum leaves reduced invasion and matrix metalloproteinase activity of head and neck cancer cell lines
Authors: Utispan Kusumawadee , Niyomtham Nattisa , Yingyongnarongkul Boon-ek , Koontongkaew Sittichai 
Published: March 2019

AbstractHead and neck squamous cell carcinoma (HNSCC) has a yearly incidence of 600,000 cases worldwide with a low survival rate. Ocimum sanctum L. or Ocimum tenuiflorum L. (Holy basil; Tulsi in Hindi), is a traditional medicine herb that demonstrates numerous effects, including anti-oxidant, anti-microbial, and anti-tumor effects. The aim of this study was to evaluate the anti-invasive effect of O. sanctum leaf extract on HNSCC cell lines. Ethanolic extract of O. sanctum leaf (EEOS) was prepared and the phenolic compounds were identified using high-performance liquid chromatography-electrospray ionization-time of flight-mass spectrometry. Genetically-matched HNSCC cell lines derived from primary (HN30 and HN4) and metastatic sites (HN31 and HN12) from the same patient were used in this study. The EEOS cytotoxicity to the cell lines was determined using an MTT assay. The invasion and matrix metalloproteinase (MMP)-2 and -9 activity of EEOS-treated cells were tested using a modified Boyden chamber assay and zymography, respectively. We found that EEOS significantly inhibited the invasion and MMP-2 and MMP-9 activity of HN4 and HN12 cells, but not HN30 and HN31 cells. Rosmarinic acid, caffeic acid, and apigenin were detected in EEOS. Moreover, rosmarinic acid was found as the major phenolic compound. Therefore, EEOS exerted its anti-invasive effect on HNSCC cells by attenuating MMP activity.
Rapidly increasing prevalence of overweight and obesity in older Ghanaian adults from 2007-2015: evidence from WHO-SAGE Waves 1 & 2
Authors: Lartey Stella T. , Magnussen Costan G. , Si Lei , Boateng Godfred O. , Graaff Barbara de , Biritwum Richard Berko , Minicuci Nadia , Kowal Paul , Blizzard Leigh , Palmer Andrew J. 
Published: March 2019

AbstractBackgroundStudies on changes in the prevalence and determinants of obesity in older adults living in sub-Saharan Africa are limited. We examined recent changes in obesity prevalence and associated factors for older adults in Ghana between 2007/08 and 2014/15.MethodsData on adults aged 50 years and older in Ghana were collected in the WHO SAGE Wave 1 (2007/08; n=4158) and Wave 2 (2014/15; n=1663). The weighted prevalence of obesity, overweight, normal weight and underweight, and of high central adiposity was compared in Waves 1 and 2. Multinomial and binomial logistic regressions were used to examine whether the determinants of weight status based on objectively measured body mass index and waist circumference changed between the two survey periods.ResultsThe prevalence of obesity (Wave 1=10.2%, 95% CI: 8.9-11.7%; Wave 2=15.0%, 95% CI: 12.6-17.7%) and overweight (Wave 1=19.6%, 95% CI: 18.0-21.4%; Wave 2=24.5%, 95% CI: 21.7-27.5%) was higher in Wave 2 than Wave 1 and more than half of the population had high central adiposity (Wave 1=57.7%, 95% CI: 55.4-60.1%; Wave 2=66.9%, 95% CI: 63.7-70.0%) in both study periods. Obesity prevalence was 16% lower in males and 55% higher in females comparing Wave 1 to Wave 2. Female sex, urban residence, and high household wealth were associated with higher odds of overweight/obesity and high central adiposity. Those aged 70+ years had lower odds of obesity in both study waves. In Wave 2, females with physical activity level were more likely to be obese.ConclusionOver the 7-year period between survey waves, the population prevalence of overweight and obesity increased by 25% and 47%, respectively, while underweight reduced by 43%. These findings differed considerably by sex, which points to differential impacts of past initiatives to reduce overweight/obesity, potential high-risk groups in Ghana, and the need to increase surveillance.
Dietary acculturation of Asian and the Middle East and North African region immigrants to Saudi Arabia: healthy or unhealthy acquired nutritional behavior?
Authors: Al Zeidan Rasmieh , Tharkar Shabana , Hersi Ahmed , Ullah Anhar 
Published: March 2019

AbstractTravel and migration influences food behavior. This study assessed the dietary acculturation of immigrants in Saudi Arabia, with regard to length of stay and health status of immigrants. This cross-sectional study included 880 university immigrant employees and their family members from Asian and Middle East and North African regions. Dietary acculturation was assessed based on knowledge and practice of methods of food preparation, type of food consumption, and nutrition label reading behavior, using a measurement tool on a 5-point Likert scale. Furthermore, a scoring system was adapted for healthy practices. Anthropometric, biochemical, and blood pressure measurements were performed as per the World Health Organization guidelines, to determine participants’ health and comorbid status. In addition, scores were calculated for healthy options. Factors influencing better awareness were determined by logistic regression analysis. The most adopted methods of food preparation after migration were barbeque (p=0.018), microwave cooking (p=0.002), and raw food consumption (salads) (p<0.001). Consumption of carbonated drinks (p=0.025), fried fatty and processed food (p=0.037), and sweets and candies (p=0.008) were significantly higher among recent immigrants of <5 years of residency. Label reading behavior of nutritional contents and low-fat options was higher among immigrants with ≥5 years duration of residency (63%; p<0.001). Although female gender, longer duration of residency in Saudi Arabia and presence of comorbidity significantly improved the overall awareness and practice scores in the binary analysis, they failed to show significance in regression model except for the presence of diabetes which improved only awareness. None of the other independent factors seem to influence healthy practices. Chronic diseases like obesity, diabetes and hypertension increased with longer duration of migration(p<0.001).New immigrants are at risk of acquiring negative dietary habits compromising health, necessitating follow-up studies to establish causation. Interventional policy measures are recommended to formulate dietary guidelines.
Francisella novicidaCas9 interrogates genomic DNA with very high specificity and can be used for mammalian genome editing
Authors: Acharya Sundaram , Mishra Arpit , Paul Deepanjan , Ansari Asgar Hussain , Azhar Mohd. , Kumar Manoj , Rauthan Riya , Sharma Namrata , Aich Meghali , Sinha Dipanjali , Sharma Saumya , Jain Shivani , Ray Arjun , Jain Suman , Ramalingam Sivaprakash , Maiti Souvik , Chakraborty Debojyoti 
Published: March 2019

SUMMARYGenome editing using the CRISPR Cas9 system has been used to manipulate eukaryotic DNA and make precise heritable changes. Although the widely usedStreptococcus pyogenesCas9 (SpCas9) and its engineered variants have been efficiently harnessed for numerous gene-editing applications across different platforms, concerns remain, regarding their putative off targeting at multiple loci across the genome. Here we report thatFrancisella novicidaCas9 (FnCas9) shows a very high specificity of binding to its intended targets and negligible binding to off-target loci. The specificity is determined by its minimal binding affinity with DNA when mismatches to the target sgRNA are present in the sgRNA:DNA heteroduplex. FnCas9 produces staggered cleavage, higher HDR rates and very low non-specific genome editing compared to SpCas9. We demonstrate FnCas9 mediated correction of the sickle cell mutation in patient derived iPSCs and propose that it can be used for precise therapeutic genome editing for a wide variety of genetic disorders.SIGNIFICANCE STATEMENTTherapeutic genome editing has been significantly accentuated by the advent of CRISPR based gene correction. However, genomic off-targeting has been a major setback for clinical translation. Although high fidelity versions of Cas9 have been rationally designed, they recognize and bind to off-targets. In this study, we characterize a naturally occurring Cas9 fromFrancisella novicida(FnCas9) that shows negligible binding affinity to off targets differing by one or more mismatches, rendering it highly specific in target recognition and editing. We show that FnCas9 can direct both HDR and NHEJ mediated DNA repair, generates higher rate of HDR and negligible off-target editing. Finally we show its potential in therapeutic genome editing by correcting the sickle cell anemia mutation in patient derived iPSCs.
Discrete and Continuous Cell Identities of the Adult Murine Striatum
Authors: Stanley Geoffrey , Gokce Ozgun , Malenka Robert C. , Südhof Thomas C. , Quake Stephen R. 
Published: March 2019

AbstractThe striatum is a large brain region containing two major cell types: D1 (dopamine receptor 1) and D2 (dopamine receptor 2) expressing spiny projection neurons (SPNs). We generated a cell type atlas of the adult murine striatum using single-cell RNA-seq of SPNs combined with quantitative RNAin situhybridization (ISH). We developed a novel computational pipeline that distinguishes discrete versus continuous cell identities in scRNA-seq data, and used it to show that SPNs in the striatum can be classified into four discrete types that reside in discrete anatomical clusters or are spatially intermingled. Within each discrete type, we find multiple independent axes of continuous cell identity that map to spatial gradients and whose genes are conserved between discrete types. These gradients correlate well to previously-mapped gradients of connectivity. Using these insights, we discovered multiple novel spatially localized region of the striatum, one of which contains patch-D2 SPNs that expressTac1, Htr7, andTh. Intriguingly, we found one subtype that strongly co-expresses both D1 and D2 dopamine receptors, and uniquely expresses a rare D2 receptor splice variant. These results collectively suggest an organizational principal of neuron identity in which major neuron types can be separated into discrete classes with little overlap and no implied spatial relationship. However these discrete classes are then continuously subdivided by multiple spatial gradients of expression defining anatomical location via a combinatorial mechanism. Finally, they suggest that neuronal circuitry has a substructure at far higher resolution than is typically interrogated which is defined by the precise identity and location of a neuron.
Identification of QTL and Underlying Genes for Root System Architecture associated with Nitrate Nutrition in Hexaploid Wheat
Authors: Griffiths Marcus , Atkinson Jonathan A. , Gardiner Laura-Jayne , Swarup Ranjan , Pound Michael P. , Wilson Michael H. , Bennett Malcolm J. , Wells Darren M. 
Published: March 2019

AbstractThe root system architecture (RSA) of a crop has a profound effect on the uptake of nutrients and consequently the potential yield. However, little is known about the genetic basis of RSA and resource adaptive responses in wheat (Triticum aestivumL.). Here, a high-throughput germination paper plant phenotyping system was used to identify seedling traits in a wheat doubled haploid mapping population, Savannah × Rialto. Significant genotypic and nitrate-N treatment variation was found across the population for seedling traits with distinct trait grouping for root size-related traits and root distribution-related traits. Quantitative trait locus (QTL) analysis identified a total of 59 seedling trait QTLs. Across two nitrate treatments, 27 root QTLs were specific to the nitrate treatment. Transcriptomic analyses for one of the QTLs on chromosome 2D found under low nitrate conditions was pursued revealing gene enrichment in N-related biological processes and 17 candidate up-regulated genes with possible involvement in a root angle response. Together, these findings provide genetic insight into root system architecture and plant adaptive responses to nitrate and provide targets that could help improve N capture in wheat.