bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel factor essential for unconventional secretion of chitinase Cts1
Authors: Reindl Michèle , Stock Janpeter , Hussnaetter Kai P. , Genc Aycin , Brachmann Andreas , Schipper Kerstin 
Published: February 2020

AbstractSubcellular targeting of proteins is essential to orchestrate cytokinesis in eukaryotic cells. During cell division ofUstilago maydis, for example, chitinases must be specifically targeted to the fragmentation zone at the site of cell division to degrade remnant chitin and thus separate mother and daughter cells. Chitinase Cts1 is exported to this location via an unconventional secretion pathway putatively operating in a lock-type manner. The underlying mechanism is largely unexplored. Here, we applied a forward genetic screen based on UV mutagenesis to identify components essential for Cts1 export. The screen revealed a novel factor termed Jps1 lacking known protein domains. Deletion of the corresponding gene confirmed its essential role for Cts1 secretion. Localization studies demonstrated that Jps1 colocalizes with Cts1 in the fragmentation zone of dividing yeast cells. While loss of Jps1 leads to exclusion of Cts1 from the fragmentation zone and strongly reduced unconventional secretion, deletion of the chitinase does not disturb Jps1 localization. Yeast-two hybrid experiments suggest that the two proteins interact. In essence, we identified a novel component of unconventional secretion that functions in the fragmentation zone to enable export of Cts1. We hypothesize that Jps1 acts as an anchoring factor, supporting the proposed novel lock-type mechanism of unconventional secretion.
Mechanisms underlying the cooperation between loss of epithelial polarity and Notch signaling during neoplastic growth in Drosophila
Authors: Logeay Rémi , Géminard Charles , Lassus Patrice , Rodríguez-Vázquez Miriam , Kantar Diala , Héron-Milhavet Lisa , Fischer Bettina , Bray Sarah J. , Colinge Jacques , Djiane Alexandre 
Published: February 2020

SUMMARYAggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch dedicated transcription factor. The Notch-dependent neoplasms require however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1, and bZIP factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally our work highlights some Notch/scrib specificities, in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.
A Wnt-BMP4 signalling axis induces MSX and NOTCH proteins and promotes growth suppression and differentiation in neuroblastoma
Authors: Szemes Marianna , Melegh Zsombor , Bellamy Jacob , Kollareddy Madhu , Catchpoole Daniel , Malik Karim 
Published: February 2020

ABSTRACTThe Wnt and bone morphogenetic protein (BMP) signalling pathways are known to be crucial in the development of neural crest lineages, including the sympathetic nervous system. Surprisingly, their role in paediatric neuroblastoma, the prototypic tumour arising from this lineage, remains relatively uncharacterised. We previously demonstrated that Wnt/β-catenin signalling can have cell-type specific effects on neuroblastoma phenotypes, including growth inhibition and differentiation, and that BMP4 mRNA and protein were induced by Wnt3a/Rspo2. In this study, we characterise the phenotypic effects of BMP4 on neuroblastoma cells, demonstrating convergent induction of MSX homeobox transcription factors by Wnt and BMP4 signalling and BMP4-induced growth suppression and differentiation. Immunohistochemical analysis of BMP4 expression in primary neuroblastomas confirms a striking absence of BMP4 in poorly differentiated tumours, in contrast to high expression in ganglion cells. These results are consistent with a tumour suppressive role for BMP4 in neuroblastoma. RNA sequencing following BMP4 treatment revealed induction of Notch signalling, verified by increases of Notch3 and Hes1 proteins. Together, our data demonstrate for the first time Wnt-BMP-Notch signalling crosstalk associated with growth suppression of neuroblastoma.
Characterization of the motor cortex transcriptome supports microgial-related key events in amyotrophic lateral sclerosis
Authors: Dols-Icardo Oriol , Montal Victor , Sirisi Sònia , López-Pernas Gema , Cervera-Carles Laura , Querol-Vilaseca Marta , Muñoz Laia , Belbin Olivia , Alcolea Daniel , Molina-Porcel Laura , Pegueroles Jordi , Turón-Sans Janina , Blesa Rafael , Lleó Alberto , Fortea Juan , Rojas-García Ricard , Clarimón Jordi 
Published: February 2020

AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. A major neuropathological finding in ALS is the coexistence of glial activation and aggregation of the phosphorylated transactive response DNA-binding protein 43-kDa (pTDP43) in the motor cortex at the earliest stages of the disease. Despite this, the transcriptional alterations associated with these pathological changes in this major vulnerable brain region have yet to be fully characterized. Here, we have performed massive RNA sequencing of the motor cortex of ALS (n=11) and healthy controls (HC; n=8). We report extensive RNA expression alterations at gene and isoform levels, characterized by the enrichment of neuroinflammatory and synapse related pathways. The assembly of gene co-expression modules confirmed the involvement of these two principal transcriptomic changes, and showed a strong negative correlation between them. Furthermore, cell-type deconvolution using human single-nucleus RNA sequencing data as reference demonstrated that microglial cells are overrepresented in ALS compared to HC. Importantly, we also show for the first time in the human ALS motor cortex, that microgliosis is mostly driven by the increased proportion of a microglial subpopulation characterized by gene markers overlapping with the recently described disease associated microglia (DAM). Using immunohistochemistry, we further evidenced that this microglial subpopulation is overrepresented in ALS and that variability in pTDP43 aggregation among patients negatively correlates with the proportion of microglial cells. In conclusion, we report that neuroinflammatory changes in ALS motor cortex are dominated by microglia which is concomitant with a reduced expression of postsynaptic transcripts, in which DAM might have a prominent role. Microgliosis therefore represents a promising avenue for therapeutic intervention in ALS.
EXO70D isoforms mediate selective autophagic degradation of Type-A ARR proteins to regulate cytokinin sensitivity
Authors: Acheampong Atiako Kwame , Shanks Carly , Chang Chai-Yi , Schaller G. Eric , Dagdas Yasin , Kieber Joseph J. 
Published: February 2020

AbstractThe phytohormone cytokinin influences many aspects of plant growth and development, several of which also involve the cellular process of autophagy, including leaf senescence, nutrient re-mobilization, and developmental transitions. The Arabidopsis type-A Response Regulators (type-A ARR) are negative regulators of cytokinin signaling that are transcriptionally induced in response to cytokinin. Here, we describe a mechanistic link between cytokinin signaling and autophagy, demonstrating that plants modulate cytokinin sensitivity through autophagic regulation of type-A ARR proteins. Type-A ARR proteins were degraded by autophagy in an AUTOPHAGY-RELATED (ATG)5-dependent manner. EXO70D family members interacted with Type-A ARR proteins, likely in a phosphorylation-dependent manner, and recruited them to autophagosomes via interaction with the core autophagy protein, ATG8. Consistently, loss-of-function exo70D1,2,3 mutants compromised targeting of type-A ARRs to autophagic vesicles, have elevated levels of type-A ARR proteins, and are hyposensitive to cytokinin. Disruption of both type-A ARRs and EXO70D1,2,3 compromised survival in carbon-deficient conditions, suggesting interaction between autophagy and cytokinin responsiveness in response to stress. These results indicate that the EXO70D proteins act as selective autophagy receptors to target type-A ARR cargos for autophagic degradation, demonstrating that cytokinin signaling can be modulated by selective autophagy.
Telomere length heterogeneity in ALT cells is maintained by PML-dependent localization of the BTR complex to telomeres
Authors: Loe Taylor K , Li Julia Su Zhou , Zhang Yuxiang , Azeroglu Benura , Boddy Michael Nicholas , Denchi Eros Lazzerini 
Published: February 2020

ABSTRACTTelomeres consist of TTAGGG repeats bound by protein complexes that serve to protect the natural end of linear chromosomes. Most cells maintain telomere repeat lengths by utilizing the enzyme telomerase, although there are some cancer cells that use a telomerase-independent mechanism of telomere extension, termed Alternative Lengthening of Telomeres (ALT). Cells that employ ALT are characterized, in part, by the presence of specialized PML nuclear bodies called ALT-associated PML-Bodies (APBs). APBs localize to and cluster telomeric ends together with telomeric and DNA damage factors, which led to the proposal that these bodies act as a platform on which ALT can occur. However, the necessity of APBs and their function in the ALT pathway has remained unclear. Here, we used CRISPR/Cas9 to delete PML and APB components from ALT-positive cells to cleanly define the function of APBs in ALT. We find that PML is required for the ALT mechanism, and that this necessity stems from APBs’ role in localizing the BLM-TOP3A-RMI (BTR) complex to ALT telomere ends. Strikingly, recruitment of the BTR complex to telomeres in a PML-independent manner bypasses the need for PML in the ALT pathway, suggesting that BTR localization to telomeres is sufficient to sustain ALT activity.
Phosphoproteomic analysis of mammalian infectiveTrypanosoma bruceisubjected to heat shock suggests atypical mechanisms for thermotolerance
Authors: Ooi Cher P. , Benz Corinna , Urbaniak Michael D. 
Published: February 2020

AbstractThe symptoms of African sleeping sickness, caused by the parasiteTrypanosoma brucei, can include periods of fever as high as 41 °C which triggers a heat shock response in the parasite. To capture events involved in sensing and responding to heat shock in the mammalian infective form we have conducted a SILAC-based quantitative proteomic and phosphoproteomic analysis ofT. bruceicells treated at 41 °C for 1h. Our analysis identified 193 heat shock responsive phosphorylation sites with an average of 5-fold change in abundance, but only 20 heat shock responsive proteins with average of 1.5-fold change. These data indicate that protein abundance does not rapidly respond (≤1 h) to heat shock, and that the changes observed in phosphorylation site abundance are larger and more widespread. The heat shock responsive phosphorylation sites showed enrichment of RNA binding proteins with putative roles in heat shock response included P-body / stress granules and the eukaryotic translation initiation 4F complex. The ZC3H11-MKT1 complex, which stabilises mRNAs of thermotolerance proteins, appears to represent a key signal integration node in the heat shock response.
A 3D human liver model of nonalcoholic steatohepatitis
Authors: Duriez Marion , Jacquet Agnes , Hoet Lucile , Roche Sandrine , Bock Marie-Dominique , Rocher Corinne , Haussy Gilles , Vigé Xavier , Bocskei Zsolt , Slavnic Tamara , Martin Valérie , Guillemot Jean-Claude , Didier Michel , Kannt Aimo , Orsini Cécile , Mikol Vincent , Le Fèvre Anne-Céline 
Published: February 2020

AbstractWe have developed anin vitropreclinical 3D Non-Alcoholic SteatoHepatitis (NASH) model by co-culturing four human primary liver cell types: hepatocytes, stellate, endothelial and Kupffer cells. Cells were embedded in a hydrogel of rat collagen in 96-well plate and a NASH-like environment was induced with a medium containing free fatty acids (FFAs) and tumor necrosis factor α (TNFα). This model was characterized by biochemical, imaging and transcriptomics analysis. On the one hand, we succeed in defining suitable culture conditions to maintain the 3D co-culture up to 10 daysin vitrowith the lowest level of steatosis, and reproducible low levels of inflammation and fibrosis. On the other hand, we induced NASH disease with a custom medium mimicking NASH features (hepatocyte injury, steatosis, inflammation and fibrosis). The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.SummaryWe developed a 3D human liver model which exhibits many features of non-alcoholic steatohepatitis and that could become a platform for medium throughput drug screening.
Phasing and imputation of single nucleotide polymorphism data of missing parents of bi-parental plant populations
Authors: Gonen Serap , Wimmer Valentin , Gaynor R. Chris , Byrne Ed , Gorjanc Gregor , Hickey John M. 
Published: February 2020

AbstractThis paper presents an extension to a heuristic method for phasing and imputation of genotypes of descendants in bi-parental populations so that it can phase and impute genotypes of parents of bi-parental populations that are fully ungenotyped or partially genotyped. The imputed genotypes of the parent are then used to impute low-density genotyped descendants of the bi-parental population to high-density. The extension works in three steps. First, it identifies whether a parent has no or low-density genotypes available and it identifies all of its relatives that have high-density genotypes. Second, using the high-density information of relatives, it determines whether the parent is homozygous or heterozygous for a given locus. Third, it phases heterozygous positions of the parent by matching haplotypes to its relatives.We implemented the new algorithm in an extension of the AlphaPlantImptue software and tested its accuracy of imputing missing parent genotypes in simulated bi-parental populations from different scenarios. We also tested the accuracy of imputation of the missing parent’s descendants using the true genotype of the parent and compared this to using the imputed genotypes of the parent. Our results show that across all scenarios, the accuracy of imputation of a parent, measured as the correlation between true and imputed genotypes, was > 0.98 and did not drop below ∼ 0.96. The imputation accuracy of a parent was always higher when it was inbred than when it was outbred and when it had low-density genotypes. Including ancestors of the parent at HD, increasing the number of crosses and the number of high-density descendants all increased the accuracy of imputation. The high imputation accuracy achieved for the parent across all scenarios translated to little or no impact on the accuracy of imputation of its descendants at low-density.Key MessageNew fast and accurate method for phasing and imputation of SNP chip genotypes within diploid bi-parental plant populations.
SPAs promote thermomorphogenesis via regulating the phyB-PIF4 module inArabidopsis
Authors: Lee Sanghwa , Paik Inyup , Huq Enamul 
Published: February 2020

SUMMARYHigh ambient temperature due to global warming has a profound influence on plant growth and development at all stages of life cycle. Plant response to high ambient temperature termed thermomorphogenesis is characterized by hypocotyl and petiole elongation, and hyponastic growth at seedling stage. However, the molecular mechanism of thermomorphogenesis is still rudimentary. Here, we show that a set of fourSUPPRESSOR OF PHYA-105(SPA) genes are required for thermomorphogenesis. Consistently, SPAs are necessary for global gene expression changes in response to high ambient temperature. SPA1 level is unaffected, while the thermosensor phyB is stabilized in thespaQmutant at high ambient temperature. Furthermore, in the absence of fourSPAgenes, the pivotal transcription factor PIF4 fails to accumulate, indicating a role of SPAs in regulating the phyB-PIF4 module at high ambient temperature. SPA1 directly phosphorylates PIF4in vitro, and a mutant SPA1 affecting the kinase activity fails to rescue the PIF4 level as well as the thermo-insensitive phenotype ofspaQ, suggesting that the SPA1 kinase activity is necessary for thermomorphogenesis. Taken together, these data suggest that SPAs integrate light and temperature signaling via fine tuning the phyB-PIF4 module.
Mitochondria dynamics in postmitotic cells drives neurogenesis through Sirtuin-dependent chromatin remodeling
Authors: Iwata Ryohei , Vanderhaeghen Pierre 
Published: February 2020

AbstractThe conversion of neural stem cells into neurons is associated with massive remodeling of organelles and chromatin, but whether and how these are linked to control neuronal fate commitment remains unknown. We examined and manipulated mitochondria dynamics with high temporal resolution during mouse and human cortical neurogenesis. We reveal that shortly after cortical stem cells have divided, daughter cells that retain high levels of mitochondria fission will become neurons, while those destined to self-renew undergo rapid mitochondria fusion. Induction of mitochondria fusion after mitosis redirects daughter cells towards cell self-renewal, but only during a restricted time window, which is doubled in human cortical stem cells with higher self-renewing potential. Mitochondria dynamics drives neurogenesis through modulation of the NAD+sensor Sirtuin-1, leading to Histone deacetylation and chromatin remodeling necessary for neurogenic conversion. Our data reveal a post-mitotic critical period of neurogenesis, linking mitochondria state with cell fate.
Improved design and analysis of practical minimizers
Authors: Zheng Hongyu , Kingsford Carl , Marçais Guillaume 
Published: February 2020

AbstractMotivationMinimizers are methods to samplek-mers from a sequence, with the guarantee that similar set ofk-mers will be chosen on similar sequences. It is parameterized by thek-mer lengthk, a window lengthwand an order on thek-mers. Minimizers are used in a large number of softwares and pipelines to improve computation efficiency and decrease memory usage. Despite the method’s popularity, many theoretical questions regarding its performance remain open. The core metric for measuring performance of a minimizer is the density, which measures the sparsity of sampledk-mers. The theoretical optimal density for a minimizer is 1/w, provably not achievable in general. For givenkandw, little is known about asymptotically optimal minimizers, that is minimizers with densityO(1/w).ResultsWe derive a necessary and sufficient condition for existence of asymptotically optimal minimizers. We also provide a randomized algorithm, called the Miniception, to design minimizers with the best theoretical guarantee to date on density in practical scenarios. Constructing and using the Miniception is as easy as constructing and using a random minimizer, which allows the design of efficient minimizers that scale to the values ofkandwused in current bioinformatics software programs.AvailabilityReference implementation of the Miniception and the codes for analysis can be found athttps://github.com/kingsford-group/miniception.Contactgmarcais@cs.cmu.edu
Canopy position has a stronger effect than tree species identity on phyllosphere bacterial diversity in a floodplain hardwood forest
Authors: Herrmann Martina , Geesink Patricia , Richter Ronny , Küsel Kirsten 
Published: February 2020

AbstractThe phyllosphere is a challenging microbial habitat in which microorganisms can flourish on organic carbon released by plant leaves but are also exposed to harsh environmental conditions. Here, we assessed the relative importance of canopy position – top, mid, and bottom at a height between 31 m and 20 m – and tree species identity for shaping the phyllosphere microbiome in a floodplain hardwood forest. Leaf material was sampled from three tree species - maple (Acer pseudoplatanus L.), oak (Quercus robur L.), and lime (Tilia cordata MILL.) - at the Leipzig canopy crane facility (Germany). Estimated bacterial species richness (Chao1) and bacterial abundances approximated by quantitative PCR of 16S rRNA genes exhibited clear vertical trends with a strong increase from the top to the mid and bottom position of the canopy. 30 Operational Taxonomic Units (OTUs) formed the core microbiome, which accounted for 77% of all sequence reads. These core OTUs showed contrasting trends in their vertical distribution within the canopy, pointing to different ecological preferences and tolerance to presumably more extreme conditions at the top position of the canopy. Co-occurrence analysis revealed distinct tree species-specific OTU networks, and 55-57% of the OTUs were unique to each tree species. Overall, the phyllosphere microbiome harbored surprisingly high fractions of Actinobacteria of up to 46%. Our results clearly demonstrate strong effects of the position in the canopy on phyllosphere bacterial communities in a floodplain hardwood forest and - in contrast to other temperate or tropical forests - a strong predominance of Actinobacteria.
Forensic implication of cadaveric behaviors of the Japanese pavement ant (Tetramorium tsushimae Emery) attending to rabbit cadavers
Authors: Park Sang‐Hyun , Moon Tae‐Young 
Published: February 2020

AbstractIt is noticed by some researchers that ants may cause some forensic confusion in understanding death scenes. In the aspect of relationship between the ant‐animal decomposition, we observed the behavior of ants congregating on dead animals. Amongst various species of ants visiting dead rabbits, Tetramorium tsushimae Emery was noticeable in producing scratched scars, mounds, and nests around dead rabbits and covering them with soils. The behaviors are likely to interfere or to disturb the usual process of decomposition succession lead by maggots. We discussed that a series of cadaveric behaviors of T. tsushimae may be used as a potential forensic hint not to misunderstand death scenes disturbed by the species.
Food allergy immunotherapy: Oral immunotherapy and epicutaneous immunotherapy
Authors: Kim Edwin H. , Burks Arvil Wesley 
Published: February 2020

AbstractIgE‐mediated food allergy remains a significant and growing problem across the globe. Of the various treatment modalities, oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) have been the best studied. Across various studies of OIT for egg, milk, and peanut allergy, strong levels of desensitization have been shown. With egg and peanut OIT, a limited remission, or sustained unresponsiveness (SU), has further been demonstrated. These advances have been further validated by successful phase 2 and phase 3 studies of peanut OIT. EPIT, using daily administrations of a proprietary patch, demonstrated efficacy as well as safety and tolerability in parallel phase 2 studies; however, its phase 3 study did not meet its primary efficacy outcome. Despite its good track record of desensitization, the safety and tolerability of OIT has remained a question. EPIT, on the other hand, has proven safe and tolerable; however, the adequacy of its desensitization has remained to be determined. As OIT and EPIT continue their march toward regulatory review, optimizations for immunotherapy and novel therapies continue to be developed providing hope for food allergy patients everywhere.