bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of SALM3 dimerization and synaptic adhesion complex formation with PTPσ
Authors: Karki Sudeep , Shkumatov Alexander V. , Bae Sungwon , Ko Jaewon , Kajander Tommi 
Published: January 2020

AbstractSynaptic adhesion molecules play an important role in the formation, maintenance and refinement of neuronal connectivity. Recently, several leucine rich repeat (LRR) domain containing neuronal adhesion molecules have been characterized including netrin G-ligands, SLITRKs and the synaptic adhesion-like molecules (SALMs). Dysregulation of these adhesion molecules have been genetically and functionally linked to various neurological disorders. Here we investigated the molecular structure and mechanism of ligand interactions for the postsynaptic SALM3 adhesion protein with its presynaptic ligand, receptor protein tyrosine phosphatase σ (PTPσ). We solved the crystal structure of the dimerized leucine rich repeat (LRR) domain of SALM3, revealing the conserved structural features and mechanism of dimerization. Furthermore, we determined the complex structure of SALM3 with PTPσ using small angle X-ray scattering, revealing a 2:2 complex similar to that observed for SALM5. Solution studies unraveled additional flexibility for the complex structure, but validated the uniform mode of action for SALM3 and SALM5 to promote synapse formation. The relevance of the key interface residues was further confirmed by mutational analysis with cellular binding assays and artificial synapse formation assays. Collectively, our results suggest that SALM3 dimerization is a pre-requisite for the SALM3-PTPσ complex to exert synaptogenic activity.
Centrosome impairment causes DNA replication stress through MLK3/MK2 signaling and R-loop formation
Authors: Tayeh Zainab , Stegmann Kim , Kleeberg Antonia , Friedrich Mascha , Choo Josephine Ann Mun Yee , Wollnik Bernd , Dobbelstein Matthias 
Published: January 2020

AbstractCentrosomes function as organizing centers of microtubules and support accurate mitosis in many animal cells. However, it remains to be explored whether and how centrosomes also facilitate the progression through different phases of the cell cycle. Here we show that impairing the composition of centrosomes, by depletion of centrosomal components or by inhibition of polo-like kinase 4 (PLK4), reduces the progression of DNA replication forks. This occurs even when the cell cycle is arrested before damaging the centrosomes, thus excluding mitotic failure as the source of replication stress. Mechanistically, the kinase MLK3 associates with centrosomes. When centrosomes are disintegrated, MLK3 activates the kinases p38 and MK2/MAPKAPK2. Transcription-dependent RNA:DNA hybrids (R-loops) are then causing DNA replication stress. Fibroblasts from patients with microcephalic primordial dwarfism (Seckel syndrome) harbouring defective centrosomes showed replication stress and diminished proliferation, which were each alleviated by inhibition of MK2. Thus, centrosomes not only facilitate mitosis, but their integrity is also supportive in DNA replication.HighlightsCentrosome defects cause replication stress independent of mitosis.MLK3, p38 and MK2 (alias MAPKAPK2) are signalling between centrosome defects and DNA replication stress through R-loop formation.Patient-derived cells with defective centrosomes display replication stress, whereas inhibition of MK2 restores their DNA replication fork progression and proliferation.Graphical abstract
Changes in partner traits drive variation in plant–nectar robber interactions across habitats
Authors: Fitch Gordon , Vandermeer John 
Published: January 2020

AbstractThe frequency and outcome of biotic interactions commonly vary with environmental conditions, even without changes to community composition. Yet the drivers of such environmentally-mediated change in biotic interactions are poorly understood, limiting our ability to predict how environmental change will impact communities. Studying nectar robbery by stingless bees ofOdontonema cuspidatum(Acanthaceae) in a coffee agroecosystem, we documented a temporally consistent difference in nectar robbing intensity between anthropogenic and seminatural habitats. Plants growing in coffee fields (anthropogenic habitat) experienced significantly more nectar robbery than plants growing in forest fragments (seminatural habitat). Using a combination of field surveys and manipulative experiments, we found that nectar robbery was higher in coffee fields primarily due to environmental effects on a) neighborhood floral context and b)O. cuspidatumfloral traits. This led to both preferential foraging by nectar robbers in coffee fields, and to changes in foraging behavior onO. cuspidatumthat increased robbery. Nectar robbery significantly reduced fruit set inO. cuspidatum. These results suggest that the effects of anthropogenic environmental change on species traits may be more important than its effect on species density in determining how interaction frequency and outcome are affected by such environmental change.
Photosynthetic protein classification using genome neighborhood-based machine learning feature
Authors: Sangphukieo Apiwat , Laomettachit Teeraphan , Ruengjitchatchawalya Marasri 
Published: January 2020

AbstractIdentification of novel photosynthetic proteins is important for understanding and improving photosynthetic efficiency. Synergistically, genomic context such as genome neighborhood can provide additional useful information to identify the photosynthetic proteins. We, therefore, expected that applying the computational approach, particularly machine learning (ML) with the genome neighborhood-based feature should facilitate the photosynthetic function assignment. Our results revealed a functional relationship between photosynthetic genes and their genomic neighbors, indicating the possibility to assign functions from their genome neighborhood profile. Therefore, we created a new method for extracting the patterns based on genome neighborhood network (GNN) and applied for the photosynthetic protein classification using ML algorithms. Random forest (RF) classifier using genome neighborhood-based features achieved the highest accuracy up to 94% in the classification of photosynthetic proteins and also showed better performance (Mathew’s correlation coefficient = 0.852) than other available tools including the sequence similarity search (0.497) and ML-based method (0.512). Furthermore, we demonstrated the ability of our model to identify novel photosynthetic proteins comparing to the other methods. Our classifier is available athttp://bicep.kmutt.ac.th/photomod_standalone,https://bit.ly/2S0I2Oxand DockerHub:https://hub.docker.com/r/asangphukieo/photomod
CRY1-CBS binding regulates circadian clock function and metabolism
Authors: Cal-Kayitmazbatir Sibel , Kulkoyluoglu-Cotul Eylem , Growe Jacqueline , Selby Christopher P. , Rhoades Seth D. , Malik Dania , Oner Hasimcan , Asimgil Hande , Francey Lauren J. , Sancar Aziz , Kruger Warren D. , Hogenesch John B. , Weljie Aalim , Anafi Ron C. , Kavakli Ibrahim Halil 
Published: January 2020

AbstractCircadian disruption influences metabolic health. Metabolism modulates circadian function. However, the mechanisms coupling circadian rhythms and metabolism remain poorly understood. Here we report that Cystathionine β-synthase (CBS), a central enzyme in one-carbon metabolism, functionally interacts with the core circadian protein Cryptochrome1 (CRY1). In cells, CBS augments CRY1 mediated repression of the CLOCK/BMAL1 complex and shortens circadian period. Notably, we find that mutant CBS-I278T protein, the most common cause of homocystinuria, does not bind CRY1 or regulate its repressor activity. TransgenicCbsZn/Znmice, while maintaining circadian locomotor activity period, exhibit reduced circadian power and increased expression of E-BOX outputs. CBS function is reciprocally influenced by CRY1 binding. CRY1 modulates enzymatic activity of the CBS. Liver extracts fromCry1−/−mice show reduced CBS activity that normalizes after the addition of exogenous wild type (WT) CRY1. Metabolomic analysis of WT,CbsZn/Zn,Cry1−/−, andCry2−/−samples highlights the metabolic importance of endogenous CRY1. We observed temporal variation in one-carbon and transsulfuration pathways attributable to CRY1 induced CBS activation. CBS-CRY1 binding provides a post-translational switch to modulate cellular circadian physiology and metabolic control.
Disassembly and degradation of MinD oscillator complexes byEscherichia coliClpXP
Authors: LaBreck Christopher J. , Trebino Catherine E. , Ferreira Colby N. , Morrison Josiah J. , DiBiasio Eric C. , Conti Joseph , Camberg Jodi L. 
Published: January 2020

AbstractMinD is a cell division ATPase inEscherichia colithat oscillates from pole to pole and regulates the spatial position of the cell division machinery. Together with MinC and MinE, the Min system restricts assembly of the FtsZ-ring to midcell, oscillating between the opposite ends of the cell and preventing FtsZ-ring misassembly at the poles. Here, we show that the ATP-dependent bacterial proteasome complex ClpXP degrades MinD in reconstituted degradation reactions in vitro, through direct recognition of the MinD N-terminal region, and in vivo. MinD degradation is enhanced during stationary phase, suggesting that ClpXP regulates levels of MinD in cells that are not actively dividing. MinC and MinD are known to co-assemble into linear polymers, therefore we monitored copolymers assembled in vitro after incubation with ClpXP and observed that ClpXP promotes rapid MinCD copolymer disassembly as a result of direct MinD degradation by ClpXP. The N-terminus of MinD, including residue Arg 3, which is near the ATP-binding site, is critical for degradation by ClpXP. Together, these results demonstrate that ClpXP degradation modifies conformational assemblies of MinD in vitro and depresses Min function in vivo during periods of reduced proliferation.
FTO-mediated cytoplasmic m6Amdemethylation adjusts stem-like properties in colorectal cancer cell
Authors: Relier Sébastien , Ripoll Julie , Guillorit Hélène , Amalric Amandine , Boissière Florence , Vialaret Jérôme , Attina Aurore , Debart Françoise , Choquet Armelle , Macari Françoise , Samalin Emmanuelle , Vasseur Jean-Jacques , Pannequin Julie , Crapez Evelyne , Hirtz Christophe , Rivals Eric , Bastide Amandine , David Alexandre 
Published: January 2020

ABSTRACTCancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications dynamic in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its m6Am(N6,2’-O-dimethyladenosine) demethylase activity. While m6Amis strategically located next to the m7G-mRNA cap, its biological function is not well understood and has not been addressed in cancer. Low FTO expression in patient-derived cell lines elevates m6Amlevel in mRNA which results in enhancedin vivotumorigenicity and chemoresistance. Inhibition of the nuclear m6Ammethyltransferase, PCIF1/CAPAM, partially reverses this phenotype. FTO-mediated regulation of m6Ammarking constitutes a novel, reversible pathway controlling CSC abilities that does not involve transcriptome remodeling, but could fine-tune translation efficiency of selected m6Ammarked transcripts. Altogether, our findings bring to light the first biological function of the m6Ammodification and its potential adverse consequences for colorectal cancer management.
Limb contraction drives fear perception
Authors: Solanas Marta Poyo , Vaessen Maarten , de Gelder Beatrice 
Published: January 2020

AbstractHumans and other primate species are experts at recognizing affective information from body movements but the underlying brain mechanisms are still largely unknown. Previous research focusing on the brain representation of symbolic emotion categories has led to mixed results. This study used representational similarity and multi-voxel pattern analysis techniques to investigate how postural and kinematic features computed from affective whole-body movement videos are related to brain processes. We show that body posture and kinematics differentially activated brain regions indicating that this information might be selectively encoded in these regions. Most specifically, the feature limb contraction seemed to be particularly relevant for distinguishing fear and it was represented in several regions spanning affective, action observation and motor preparation networks. Our approach goes beyond traditional methods of mapping symbolic emotion categories to brain activation/deactivation by discovering which specific movement features are encoded in the brain, and possibly drive automatic emotion perception.
ModelTeller: model selection for optimal phylogenetic reconstruction using machine learning
Authors: Abadi Shiran , Avram Oren , Rosset Saharon , Pupko Tal , Mayrose Itay 
Published: January 2020

AbstractStatistical criteria have long been the standard for selecting the best model for phylogenetic reconstruction and downstream statistical inference. While model selection is regarded as a fundamental step in phylogenetics, existing methods for this task consume computational resources for long processing time, they are not always feasible, and sometimes depend on preliminary assumptions which do not hold for sequence data. Moreover, while these methods are dedicated to revealing the processes that underlie the sequence data, in most cases they do not produce the most accurate trees. Notably, phylogeny reconstruction consists of two related tasks, topology reconstruction and branch-length estimation. It was previously shown that in many cases the most complex model, GTR+I+G, leads to topologies that are as accurate as using existing model selection criteria, but overestimates branch lengths. Here, we present ModelTeller, a computational methodology for phylogenetic model selection, devised within the machine-learning framework, optimized to predict the most accurate model for branch-length estimation accuracy. ModelTeller relies on a readily implemented machine-learning model and thus the prediction according to features extracted from the sequence data results in a substantial decrease in running time compared to existing strategies. We show that on datasets simulated under simple homogenous substitution models ModelTeller leads to branch-length estimation that is as accurate as the statistical model selection criteria. We then demonstrate that ModelTeller outperforms these criteria when more intricate patterns – that aim at mimicking realistic processes – are considered.
Dual-light photodynamic therapy administered daily provides a sustained antibacterial effect on biofilm and preventsStreptococcus mutansadaptation
Authors: Nikinmaa S , Alapulli H , Auvinen P , Vaara M , Rantala J , Kankuri E , Sorsa T , Meurman J , Pätilä T 
Published: January 2020

AbstractIntroductionAntibacterial photodynamic therapy (aPDT) and antibacterial blue light (aBL) are emerging treatment methods auxiliary to mechanical debridement for periodontitis. APDT provided with a near infrared (NIR) light in conjunction with an indocyanine green (ICG) photosensitizer has shown efficacy in several dental in-office-treatment protocols. In this study, we testedStreptococcus mutansbiofilm sensitivity to either single-light (aPDT or aBL) or dual-light aPDT (simultaneous aPDT and aBL) exposure.Materials and MethodsBiofilm was cultured by pipeting dilutedStreptococcus mutanssuspension with growth medium on the bottom of well plates. Either a single-light aPDT (810-nm aPDT or 405-nm aBL) or a dual-light aPDT (simultaneous 810-nm aPDT and 405nm aBL) was applied, in both cases together with the ICG photosensitizer, while keeping the total light energy constant at 100J/cm2. Single-dose light exposures were given after one-day, four-day or fourteen-day biofilm incubations. Also, a repeated daily dose of the same light energy was applied during biofilm incubations on four-day and fourteen-day biofilms. Finally, antibacterial action of the dual-light aPDT with different relative ratios of 810 nm and 405 nm of light energy was examined on the single-day and four-day protocols. Biofilms were scraped, diluted into ratios between 1:1 to 1:100 000, and plated. After re-incubation, colony-forming units (CFUs) were counted, and confocal 3D biofilm imaging was performed.ResultsOn a one-day biofilm, dual-light aPDT was significantly more efficient than single-light aBL or aPDT, although all modalities were bactericidal. On a four-day maturated biofilm, a single exposure of aPDT or dual-light aPDT was more efficient than aBL, resulting in a four logarithmic scale reduction in bacterial counts. Surprisingly, when the same amount of aPDT was repeated with a daily dosing on a four-day or a fourteen-day biofilm, bacterial viability improved significantly. A similar but milder response of improved bacterial viability was seen after repetitive aBL application. The viability improvement was eliminated when dual-light aPDT was applied. By changing the relative light energy ratios in dual-light aPDT, a relative increase in aBL improved the antibacterial action of dual-light aPDT when the biofilm was older.ConclusionWhen aPDT is administered repeatedly toS. mutansbiofilm, a single wavelength-based aBL or aPDT leads to a significant biofilm adaptation and increasedS. mutansviability. The combined use of aBL light in synchrony with aPDT arrests the adaptation and provides significantly improved and sustained antibacterial efficacy.
Limited dispersal and an unexpected aggression pattern in a native supercolonial ant
Authors: Hakala S. M. , Ittonen M. , Seppä P. , Helanterä H. 
Published: January 2020

ABSTRACTUnderstanding how social groups function requires studies on how individuals move across the landscape and interact with each other. Ant supercolonies are extreme cooperative units that may consist of thousands of interconnected nests, and their individuals cooperate over large spatial scales. However, the inner structure of suggested supercolonial (or unicolonial) societies has rarely been extensively studied using both genetic and behavioral analyses. We describe a dense supercolony-like aggregation of more than 1 300 nests of the antFormica(Coptoformica)pressilabris. We performed aggression bioassays and found that, while aggression levels were generally low, there was some aggression within the assumed supercolony. The occurrence of aggression increased with distance from the focal nest, in accordance with the genetically viscous population structure we observe by using 10 microsatellite markers. However, the aggressive interactions do not follow any clear pattern that would allow specifying colony borders within the area. The genetic data indicate limited gene flow within and away from the supercolony. Our results show that aFormicasupercolony is not necessarily a single unit but can be a more fluid mosaic of aggressive and amicable interactions instead, highlighting the need to study internest interactions in detail when describing supercolonies.
Physiotherapist and Podiatrist Independent Prescribing in the United Kingdom: A quasi experimental study
Authors: Carey Nicola , Edwards Judith , Otter Simon , Gage Heather , Williams Peter , Courtenay Molly , Moore Ann , Stenner Karen 
Published: January 2020

AbstractBackgroundIncreasing numbers of nurses, pharmacists and allied health professionals across the world have prescribing rights: over 90,000 of the eligible United Kingdom workforce are qualified as non-doctor prescribers. In order to inform future developments, it is important to understand the benefits and impact of prescribing by allied health professionals including physiotherapists and podiatrists.Aim:to compare outcomes of Physiotherapist and Podiatrist Independent Prescriber (PP-IP) patients with those of Physiotherapist and Podiatrist non-prescribers (PP-NPs). Outcome measures included patient satisfaction, ease of access to services, quality of life and cost implications.Design:a quasi-experimental, post-test control group designMethods:Using mixed methods outcomes were compared between 7 sites where care was provided from a PP-IP (3 podiatrist and 4 physiotherapist IPs) and 7 sites from a PP-NP (3 podiatrist and 4 physiotherapist NPs). Patients were followed up for 2 months (2015-2016).Results:489 patients were recruited: n=243 IP sites, and n=246 NP sites. Independent prescribing was found to be highly acceptable, and equivalent in terms of quality of life (p>0.05) and patient satisfaction (p≤0.05) compared to care provided by NPs. PP-IP care delivery was found to be more resource intensive than NP-PP, with longer consultation duration for IPs (around 6.5 mins), and a higher proportion of physiotherapy patients discussed with medical colleagues (around 9.5 minutes).ConclusionThis study provides new knowledge that PP-IPs provide high levels of care. PP-IP care delivery was found to be more resource intensive. Further research is required to explore cost effectiveness. A more focussed exploration within each profession using targeted outcome measures would enable a more robust comparison, inform future developments around the world and help ensure non-doctor prescribing is recognised as an effective way to alleviate shortfalls in the global workforce.
G9a Promotes Breast Cancer Recurrence Through Repression of a Pro-inflammatory Program
Authors: Mabe Nathaniel W. , Wolery Shayna E. , Newcomb Rachel , Meingasner Ryan C. , Vilona Brittany A. , Lin Chao-Chieh , Lupo Ryan , Chi Jen-Tsan , Alvarez James V. 
Published: January 2020

AbstractEpigenetic dysregulation is a common feature of cancer, and is thought to underlie many aspects of tumor progression. Using a genetically engineered mouse model of breast cancer recurrence, we show that recurrent mammary tumors undergo widespread epigenomic and transcriptional alterations, and acquire dependence on the G9a histone methyltransferase. Genetic ablation of G9a delays tumor recurrence, and pharmacologic inhibition of G9a slows the growth of recurrent tumors. Mechanistically, G9a activity is required to silence pro-inflammatory cytokines, including TNF, through H3K9 methylation at gene promoters. G9a inhibition induces re-expression of these cytokines, leading to p53 activation and necroptosis. Recurrent tumors upregulate receptor interacting protein kinase-3 (RIPK3) expression and are dependent upon RIPK3 activity. High RIPK3 expression renders recurrent tumors sensitive to necroptosis following G9a inhibition. These findings demonstrate that epigenetic rewiring – specifically G9a-mediated silencing of pro-necroptotic proteins – is a critical step in tumor recurrence and suggest that G9a is a targetable dependency in recurrent breast cancer.