bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ensemble learning for robust knee cartilage segmentation: data from the osteoarthritis initiative
Authors: Peake Edward J , Chevasson Raphael , Pszczolkowski Stefan , Auer Dorothee P , Arthofer Christoph 
Published: September 2020

AbstractPurposeTo evaluate the performance of an ensemble learning approach for fully automated cartilage segmentation on knee magnetic resonance images of patients with osteoarthritis.Materials and MethodsThis retrospective study of 88 participants with knee osteoarthritis involved the study of three-dimensional (3D) double echo steady state (DESS) MR imaging volumes with manual segmentations for 6 different compartments of cartilage (Data available from the Osteoarthritis Initiative). We propose ensemble learning to boost the sensitivity of our deep learning method by combining predictions from two models, a U-Net for the segmentation of two labels (cartilage vs background) and a multi-label U-Net for specific cartilage compartments. Segmentation accuracy is evaluated using Dice coefficient, while volumetric measures and Bland Altman plots provide complimentary information when assessing segmentation results.ResultsOur model showed excellent accuracy for all 6 cartilage locations: femoral 0.88, medial tibial 0.84, lateral tibial 0.88, patellar 0.85, medial meniscal 0.85 and lateral meniscal 0.90. The average volume correlation was 0.988, overestimating volume by 9% ± 14% over all compartments. Simple post processing creates a single 3D connected component per compartment resulting in higher anatomical face validity.ConclusionOur model produces automated segmentation with high Dice coefficients when compared to expert manual annotations and leads to the recovery of missing labels in the manual annotations, while also creating smoother, more realistic boundaries avoiding slice discontinuity artifacts present in the manual annotations.Key ResultsCombining a 2-label U-Net (cartilage vs background) with a multi-class U-Net for segmentation of cartilage compartment boosts the accuracy of our deep learning model leading to the recovery of missing annotations in the manual dataset.Automatically generated segmentations have high Dice coefficients (0.85-0.90) and reduce inter-slice discontinuity artefact caused by slice wise delineation.Model refinement yields more anatomically plausible segmentations where each cartilage label is composed of only a single 3D region of interest.
Synchrony in the periphery: inter-subject correlation of physiological responses during live music concerts
Authors: Czepiel Anna , Fink Lauren K. , Fink Lea T. , Wald-Fuhrmann Melanie , Tröndle Martin , Merrill Julia 
Published: September 2020

AbstractA concert is a common event at which people gather to share a musical experience. While techniques are increasingly offering insights into naturalistic stimuli perception, this study extended methods to a more ecological context in order to explore real-world music listening within a concert setting. Cardiorespiratory, skin conductance, and facial muscle responses were measured from participants attending one of three concerts with live chamber music performances of works of varying Western Classical styles (Viennese Classical, Contemporary, and Romantic). Collective physiological synchronisation of audience members was operationalised via inter-subject correlation (ISC). By assessing which musical features (obtained via Music Information Retrieval and music-theoretical analyses) evoked moments of high synchrony, logistic regressions revealed that tempo consistently predicted physiological synchrony across all concerts in Classical and Romantic styles, but not the Contemporary style. Highly synchronised responses across all three concert audiences seemed to occur during structural transitional passages, boundaries, and at phrase repetitions. The results support the idea that group synchronisation is linked to musical arousal, structural coherence, and familiarity. By employing physiological ISC and an inter-disciplinary musical analysis, the current study demonstrates a novel approach to gain valuable insight into experiences of naturalistic stimuli in an ecological context.
mtDNA replication in dysfunctional mitochondria promotes deleterious heteroplasmy via the UPRmt
Authors: Yang Qiyuan , Liu Pengpeng , Anderson Nadine S. , Shpilka Tomer , Du YunGuang , Naresh Nandhitha Uma , Luk Kevin , Lavelle Josh , Zeinert Rilee D. , Chien Peter , Wolfe Scot A. , Haynes Cole M. 
Published: September 2020

ABSTRACTThe accumulation of deleterious mitochondrial genomes (ΔmtDNAs) underlies inherited mitochondrial diseases and contributes to the aging-associated decline in mitochondrial function. In heteroplasmic cells, oxidative phosphorylation (OXPHOS) function declines as the population of ΔmtDNAs increase relative to wildtype mtDNAs. In response to mitochondrial perturbations, the bZIP protein ATFS-1 induces a transcription program to promote the recovery of mitochondrial function. Paradoxically, ATFS-1 is also required to maintain ΔmtDNAs in heteroplasmic worms. However, the mechanism(s) by which ATFS-1 promotes ΔmtDNA accumulation relative to wildtype mtDNAs is unclear. Here, we show that mitochondrial-localized ATFS-1 binds almost exclusively to ΔmtDNAs in heteroplasmic worms. Moreover, we demonstrate that mitochondrial ATFS-1 promotes the preferential binding of the mtDNA replicative polymerase (POLG) to ΔmtDNAs. Interestingly, inhibition of the mtDNA-bound protease LONP-1 increased ATFS-1 and POLG binding to wildtype mtDNAs. Furthermore, LONP-1 inhibition inC. elegansand human cybrid cells improved the heteroplasmy ratio and restored OXPHOS function. Our findings suggest that ATFS-1 promotes mtDNA replication by recruiting POLG to mtDNA in a manner that is antagonized by LONP-1. We speculate that this mechanism promotes the repair and expansion of the mitochondrial network by synchronizing mtDNA replication with UPRmtactivation driven by nuclear ATFS-1 activity. However, this repair mechanism cannot resolve OXPHOS defects in mitochondria harboring ΔmtDNAs, resulting in an accumulation of ATFS-1 in dysfunctional mitochondria and constitutive replication of ΔmtDNAs.
THE MODEL OFPPARγDOWNREGULATED SIGNALING IN PSORIASIS
Authors: Sobolev Vladimir , Nesterova Anastasia , Soboleva Anna , Dvoriankova Evgenia , Piruzyan Anastas , Mildzikhova Dzerassa , Korsunskaya Irina , Svitich Oxana 
Published: September 2020

ABSTRACTInteractions of genes in intersecting signaling pathways, as well as environmental influences, are required for the development of psoriasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and transcription factor which inhibits the expression of many proinflammatory genes. We tested the hypothesis that low levels ofPPARγexpression promote the development of psoriatic lesions. We combined experimental results and network functional analysis to reconstruct the model ofPPARγdownregulated signaling in psoriasis. We hypothesize that the expression ofIL17, STAT3, FOXP3, andRORCandFOSL1genes in psoriatic skin are correlated with the level ofPPARγexpression and they belong to the same signaling pathway that regulates the development of psoriasis lesion.
Dynamic fluctuations of the locus coeruleus-norepinephrine system underlie sleep state transitions
Authors: Kjaerby Celia , Andersen Mie , Hauglund Natalie , Ding Fengfei , Wang Wei , Xu Qiwu , Deng Saiyue , Kang Ning , Peng Sisi , Sun Qian , Dall Camilla , Jørgensen Peter Kusk , Feng Jiesi , Li Yulong , Weikop Pia , Hirase Hajime , Nedergaard Maiken 
Published: September 2020

SummaryWe normally regard sleep and wake as two distinct opposing brain states, where sleep requires silence of wake-promoting structures such as the locus coeruleus (LC)-norepinephrine (NE) system. We set out to investigate how cortical NE dynamics and NE-related astrocytic activity relates to LC population activity during sleep states.We show that LC displays regular phasic activity bouts during NREM sleep leading to a slow oscillatory pattern of prefrontal NE levels of which the majority of NE increases does not lead to awakening. NE troughs link to sleep spindles and continued NE decline transitions into REM sleep. Last, we show that prefrontal astrocytes have reduced sensitivity towards NE during sleep.Our results suggest that dynamic changes in the activity of wake-promoting systems during sleep create alternation between crucial sleep processes and broadening of sensitivity towards incoming sensory input.HighlightsExtracellular levels of norepinephrine display dynamic changes during NREM and REM sleepPhasic activity of locus coeruleus neurons during NREM underlies slow norepinephrine oscillationsSpindles occur at norepinephrine troughs and are abolished by norepinephrine increasesIncreased spindles prior to REM reflect the beginning of a long-lasting norepinephrine declineREM episodes are characterized by a sub-threshold continuous norepinephrine declineThe responsiveness of astrocytic Ca2+to norepinephrine is reduced during sleep
Essential role for FtsL in activation of septal PG synthesis
Authors: Park Kyung-Tae , Du Shishen , Lutkenhaus Joe 
Published: September 2020

AbstractSpatiotemporal regulation of septal PG synthesis is achieved by coupling assembly and activation of the synthetic enzymes (FtsWI) to the Z ring, a cytoskeletal element required for division in most bacteria. InE. colithe recruitment of the FtsWI complex is dependent upon the cytoplasmic domain of FtsL, a component of the conserved FtsQLB complex. Once assembled, FtsWI is activated by the arrival of FtsN, which acts through FtsQLB and FtsA that are also essential for their recruitment. However, the mechanism of activation of FtsWI by FtsN is not clear. Here, we identify a region of FtsL that plays a key role in the activation of FtsWI which we designate AWI (Activation of FtsWI) and present evidence that FtsL acts through FtsI. Our results suggest that FtsN switches FtsQLB from a recruitment complex to an activator with FtsL interacting with FtsI to activate FtsW. Since FtsQLB and FtsWI are widely conserved in bacteria this mechanism is likely to be also widely conserved.SignificanceA critical step in bacterial cytokinesis is the activation of septal peptidoglycan synthesis at the Z ring. Although FtsN is the trigger and acts through FtsQLB and FtsA to activate FtsWI the mechanism is unclear. Here we find an essential role for FtsL in activating septal PG synthesis and find that it acts on FtsI. Our results suggest a model where FtsWI is recruited in an inactive form by FtsQLB and upon FtsN arrival, FtsQLB undergoes a conformational change so that a region of FtsL, that we designate the AWI domain, becomes available to interact with FtsI and activate the FtsWI complex. This mechanism for activation of the divisome has similarities to activation of the elongasome and is likely to be widely conserved in bacteria.
Regression plane concept: analysing continuous cellular processes with machine learning
Authors: Szkalisity Abel , Piccinini Filippo , Beleon Attila , Balassa Tamas , Varga Istvan Gergely , Migh Ede , Paavolainen Lassi , Timonen Sanna , Banerjee Indranil , Yamauchi Yohei , Ando Istvan , Peltonen Jaakko , Pietiäinen Vilja , Honti Viktor , Horvath Peter 
Published: September 2020

ABSTRACTBiological processes are inherently continuous, and the chance of phenotypic discovery is significantly restricted by discretising them. Using multi-parametric active regression we introduce a novel concept to describe and explore biological data in a continuous manner. We have implementedRegression Plane (RP), the first user-friendly discovery tool enabling class-free phenotypic supervised machine learning.
Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17
Authors: Niu Jingwen , Sanders Shaun S. , Jeong Hey-Kyeong , Holland Sabrina M. , Sun Yue , Collura Kaitlin M. , Hernandez Luiselys , Huang Haoliang , Hayden Michael R. , Smith George M. , Hu Yang , Jin Yishi , Thomas Gareth M. 
Published: September 2020

SummaryAfter optic nerve crush (ONC), the cell bodies and distal axons of most retinal ganglion cells (RGCs) degenerate. RGC somal and distal axon degeneration were previously thought to be controlled by two distinct pathways, involving activation of the kinase DLK and loss of the axon survival factor NMNAT2, respectively. However, we found that mutual palmitoylation by the palmitoyl acyltransferase ZDHHC17 couples the DLK and NMNAT2 signals, which together form a “trust, but verify system”. In healthy optic nerves, ZDHHC17-dependent palmitoylation ensures NMNAT-dependent distal axon integrity, while following ONC, ZDHHC17-dependent palmitoylation is critical for DLK-dependent somal degeneration. We found that ZDHHC17 also controls survival-versus-degeneration decisions in sensory neurons and identified motifs in NMNAT2 and DLK that govern their ZDHHC17-dependent regulation. These findings suggest that the control of somal and distal axon integrity should be considered as a single, holistic process, involving two palmitoylation-dependent pathways acting in concert.
L1PA2 transposons contribute abundant regulatory sequences in MCF7 breast cancer cell line
Authors: Jiang Jiayue-Clara , Rothnagel Joseph , Upton Kyle 
Published: September 2020

ABSTRACTTransposons, a type of repetitive DNA elements, can contribute cis-regulatory sequences and regulate the expression of human genes. L1PA2 is a hominoid-specific subfamily of LINE1 transposons, with approximately 4,940 copies in the human genome. Individual transposons have been demonstrated to contribute specific biological functions, such as cancer-specific alternate promoter activity for theMEToncogene, which is correlated with enhanced malignancy and poor prognosis in cancer. Given the sequence similarity between L1PA2 elements, we hypothesise that transposons within the L1PA2 subfamily likely have a common regulatory potential and may provide a mechanism for global genome regulation. Here we show that in breast cancer, the regulatory potential of L1PA2 is not limited to single transposons, but is common within the subfamily. We demonstrate that the L1PA2 subfamily is an abundant reservoir of transcription factor binding sites, the majority of which cluster in the LINE1 5’UTR. In MCF7 breast cancer cells, over 27% of L1PA2 transposons harbour binding sites of functionally interacting, cancer-associated transcription factors. The ubiquitous and replicative nature of L1PA2 makes them an exemplary vector to disperse co-localised transcription factor binding sites, facilitating the co-ordinated regulation of genes. In MCF7 cells, L1PA2 transposons also supply transcription start sites to up-regulated transcripts. These transcriptionally active L1PA2 transposons display a cancer-specific active epigenetic profile, and likely play an oncogenic role in breast cancer aetiology. Overall, we show that the L1PA2 subfamily contributes abundant regulatory sequences in breast cancer cells, and likely plays a global role in modulating the tumorigenic state in breast cancer.
Combination of photoactivation with lattice light-sheet imaging reveals untemplated, lamellar ruffle generation by PA-Rac1
Authors: Leyden Finian , Uthishtran Sanjeev , Moorthi U K , York H M , Patil A , Gandhi H , Petrov EP , Arumugam S 
Published: September 2020

ABSTRACTMembrane protrusions that occur on the dorsal surface of a cell are an excellent experimental system to study actin machinery at work in a living cell. Small GTPase Rac1 controls the membrane protrusions that form and encapsulate extracellular volumes to perform pinocytic or phagocytic functions. Here, capitalizing on rapid volumetric imaging capabilities of lattice light-sheet microscopy (LLSM), we describe optogenetic approaches using photoactivable Rac1 (PA-Rac1) for controlled ruffle generation. We demonstrate that PA-Rac1 activation needs to be continuous, suggesting a threshold local concentration for sustained actin polymerization leading to ruffling. We show that Rac1 activation leads to actin assembly at the dorsal surface of the cell membrane that result in sheet-like protrusion formation without any requirement of a template. Further, this approach can be used to study the complex morpho-dynamics of the protrusions or to investigate specific proteins that may be enriched in the ruffles. Deactivating PA-Rac1 leads to complex contractile processes resulting in formation of macropinosomes. Using multicolour imaging in combination with these approaches, we find that Myo1e specifically is enriched in the ruffles.
Quantifying the impacts of urban human-wildlife conflicts – how can we solve the urban gull problem in St Andrews?
Authors: Smith Grania P. 
Published: September 2020

AbstractInteractions between urban wildlife and people are increasing globally. Some of these interactions can be negative and lead to human-wildlife conflicts. In St Andrews, Scotland, residents and business owners have come into conflict with herring gulls (Larus argentatus) and lesser black-backed gulls (Larus fuscus) that nest and forage in the town. This study quantified the number, species and distribution of nesting gulls; the vulnerability of different sources of rubbish to attack; and the likelihood of negative human-gull interactions related to food. Surveys were conducted in St Andrews during the 2016 breeding season (May-July). Nesting gull density and distribution were estimated during weekly street surveys of buildings; vantage surveys were conducted for some buildings and a correction factor estimating a minimum number of nesting gulls was produced. 110 nesting gull pairs were estimated and these occupied ~10% of buildings. The vulnerability of waste sources to attack was monitored during transects recording whether or not rubbish sources were attacked. Black bin bags had the highest probability of being attacked, but placing these in secured hessian bags prevented this. The frequency of negative human-gull interactions involving food at street-level was determined during 10-minute timed watches at various locations. Incidences of gulls taking food were rare; only eight were seen in 30 hours of watches. Altering human behaviour (for example, disposing of waste securely) will mitigate potential issues with urban wildlife. Findings from this study will enable effective management of human-gull conflicts in St Andrews and have potential applications in other urban communities.
The CONDOR pipeline for simultaneous knockdown of multiple genes identifies RBBP-5 as a germ cell reprogramming barrier inC. elegans
Authors: Kazmierczak Marlon , Díaz Carlota Farré i , Ofenbauer Andreas , Tursun Baris 
Published: September 2020

ABSTRACTMultiple gene activities control complex biological processes such as cell fate specification during development and cellular reprogramming. Investigating the manifold gene functions in biological systems requires also simultaneous depletion of two or more gene activities. RNA interference-mediated knockdown (RNAi) is commonly used inC. elegansto assess essential genes, which otherwise lead to lethality or developmental arrest upon full knockout. RNAi application is straightforward by feeding worms with RNAi plasmid-containing bacteria. However, the general approach of mixing bacterial RNAi clones to deplete two genes simultaneously often yields poor results. To address this issue, we developed a bacterial conjugation-mediated double RNAi technique ‘CONDOR’. It allows combining RNAi bacteria for robust double RNAi with high-throughput. To demonstrate the power of CONDOR for large scale double RNAi screens we conjugated RNAi against the histone chaperone genelin-53with more than 700 other chromatin factor genes. Thereby, we identified the Set1/MLL methyltransferase complex member RBBP-5 as a novel germ cell reprogramming barrier. Our findings demonstrate that CONDOR increases efficiency and versatility of RNAi screens to examine interconnected biological processes inC. eleganswith high-throughput.
Potential malaria vectorAnopheles minimus(species A) still persisting in North East India
Authors: Tyagi Varun , Goswami Diganta , Dhiman Sunil , Dey Dipanjan , Rabha Bipul , Chattopadhyay P. , Dwivedi Sanjai K 
Published: September 2020

ABSTRACTBackgroundVector borne infectious diseases affect two third of the world’s human population and cause mortality in millions each year. Malaria remains one of the major killers in the Indian sub-continent and transmitted uninterruptedly by many efficient vectors and their sibling species. In North East India (NE),Anopheles minimushas been recognized as an important vector which shares majority of malaria cases. This study primarily focuses on to recognize the presence and distribution of sibling species ofAn. minimusin certain endemic area of NE India.MethodsAnophelesspecies were collected and identified using available morphological keys. The genomic DNA was extracted from the mosquito specimen and used to perform species specific PCR (ss PCR) for molecular identification of major malaria vectorAn. minimussibling speciesResultMorphological identification suggested the presence ofAn. minimus slin low density in the study area. The specimen ofAn. minimussubjected to ss PCR confirmed the prevalence of only one sibling species namely,An. minimusA in Sialmari and Chandubi.ConclusionThough in low density, but malaria vectorAn. minimusis still present in certain endemic areas of NE India. The ss PCR assay employed presently suggested thatAn. minimussibling species A is prevailing in the region. Presently used ss PCR assay was simpler, faster, cheaper and more readily interpreted than earlier assays. This information could be useful in understanding of current prevalence and distribution ofAn. minimussibling species complex in NE region of India.
Maintaining robust size across environmental conditions through plastic brain growth dynamics
Authors: Cobham Ansa E. , Neumann Brent , Mirth Christen K. 
Published: September 2020

AbstractOrgan growth is tightly regulated across environmental conditions to generate appropriate final size. While the size of some organs is free to vary, others need to maintain constant size to function properly. This poses a unique problem: how is robust final size achieved when environmental conditions can alter some major growth processes? While we know that brain growth is “spared” from the effects of the environment from humans to fruit flies, we do not understand how this process alters growth dynamics across brain compartments. Here, we explore how this robustness in brain size is achieved by examining differences in growth patterns between the larval body, the brain, and a brain compartment – the mushroom bodies – inDrosophila melanogasteracross both thermal and nutritional conditions. We identify key differences in patterns of growth between the whole brain and mushroom bodies that are likely to underlie robustness of final organ shape. Further, we show that these differences produce distinct brain shapes across environments.Significance of StudyA long-standing question in Biology has been how fully functional multicellular organisms with highly specialized organs are generated, given that organs initiate growth at different times across development. Although the genetic mechanisms that underlie growth has been studied extensively, we are yet to understand how growth pattern of organs produces distinct final shapes across changing environmental conditions. We use the Drosophila brain, to reveal that key differences in growth dynamics are likely to underlie robustness of final organ shape and are tuned by nutrition and temperature. Further deepening our knowledge of how final organ shape is maintained across environmental conditions.