bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular senescence is a central response to cytotoxic chemotherapy in high-grade serous ovarian cancer
Authors: Calvo L. , Cheng S. , Skulimowski M. , Clément I. , Portelance L. , Zhan Y. , Carmona E. , Lafontaine J. , de Ladurantaye M. , Rahimi K. , Provencher D. , Mes-Masson A.-M. , Rodier F. 
Published: September 2018

AbstractHigh-grade serous ovarian cancer (HGSOC) commonly responds to initial therapy, but this response is rarely durable. Understanding cell fate decisions taken by HGSOC cells in response to treatment could guide new therapeutic opportunities. Here we find that primary HGSOC cultures undergo therapy-induced senescence (TIS) in response to DNA damage induced by chemotherapy. HGSOC-TIS displays most senescence hallmarks including persistent DNA damage, senescence-associated inflammatory secretome, and selective sensitivity to senolytic Bcl-2 family inhibitors, suggesting avenues for preferential synergistic clearance of these cells. Comparison of pre- and post-chemotherapy HGSOC patient tissue samples revealed changes in senescence biomarkers suggestive of post-treatment “in patient” TIS, and a stronger TIS response in post-chemotherapy tissues correlated with better 5-year survival rates for patients. Together, these data suggest that the induction of cellular senescence in HGSOC cells accounts at least in part for beneficial cellular responses to treatment in patients providing a new therapeutic target.One Sentence SummaryCellular senescence is a central beneficial response to chemotherapy in high-grade serous ovarian cancer bothin vitroand in patient.
Evolutionary dynamics of recent selection for enhanced social cognition
Authors: Miller Sara E. , Legan Andrew W. , Henshaw Michael , Ostevik Katherine L. , Samuk Kieran , Uy Floria M. K. , Reeve H. Kern , Sheehan Michael J. 
Published: September 2018

AbstractCognitive abilities can vary dramatically among species though little is known about the dynamics of cognitive evolution. Here we demonstrate that recent evolution of visual individual recognition in the paper waspPolistes fuscatusis the target of arguably the strongest positive selective pressure in the species’ recent history. The most extreme selective sweeps inP. fuscatusare associated with genes known to be involved in long-term memory formation, mushroom body development and visual processing – all traits that have recently evolved in association with individual recognition. Cognitive evolution appears to have been driven initially by selection on standing variation in perceptual traits followed by both hard and soft sweeps on learning and memory. Evolutionary modeling reveals that intense selection as observed inP. fuscatusis likely the norm during the early stages of cognitive evolution. These data provide insight into the dynamics of cognition evolution demonstrating that social selection for increased intelligence can lead to rapid multi-genic adaptation of enhanced recognition abilities.
Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection
Authors: Masamsetti V. Pragathi , Mak Ka Sin , Jie Low Ronnie Ren , Riffkin Chris D. , Lamm Noa , Crabbe Laure , Karlseder Jan , Huang David C.S. , Hayashi Makoto T. , Cesare Anthony J. 
Published: September 2018

ABSTRACTMitotic catastrophe is a broad descriptor encompassing unclear mechanisms of cell death. Here we investigate replication stress-driven mitotic catastrophe in human cells and identify that replication stress principally induces mitotic death signalled through two independent pathways. In p53-compromised cells we find that lethal replication stress confers WAPL-dependent centromere cohesion defects that maintain spindle assembly checkpoint-dependent mitotic arrest in the same cell cycle. Mitotic arrest then drives cohesion fatigue and triggers mitotic death through a primary pathway of BAX/BAK-dependent apoptosis. Simultaneously, a secondary mitotic death pathway is engaged through non-canonical telomere deprotection, regulated by TRF2, Aurora B and ATM. Additionally, we find that suppressing mitotic death promotes genome instability in replication stressed cells through diverse mechanisms depending upon how cell death is averted. These data demonstrate how replication stress-induced mitotic catastrophe signals cell death with implications for cancer treatment and genome instability.
Automated leg tracking reveals distinct conserved gait and tremor signatures inDrosophilamodels of Parkinson’s Disease and Spinocerebellar ataxia 3
Authors: Wu Shuang , Tan Kah Junn , Govindarajan Lakshmi Narasimhan , Stewart James Charles , Gu Lin , Hao Ho Joses Wei , Katarya Malvika , Wong Boon Hui , Tan Eng-King , Li Daiqin , Claridge-Chang Adam , Libedinsky Camilo , Cheng Li , Aw Sherry Shiying 
Published: September 2018

SummaryGenetic models inDrosophilahave made invaluable contributions to our understanding of the molecular mechanisms underlying neurodegeneration. In human patients, some neurodegenerative diseases lead to characteristic movement dysfunctions, such as abnormal gait and tremors. However, it is currently unknown whether similar movement defects occur in the respective fly models, which could be used to model and better understand the pathophysiology of movement disorders. To address this question, we developed a machine-learning image-analysis programme — Feature Learning-based LImb segmentation and Tracking (FLLIT) — that automatically tracks leg claw positions of freely moving flies recorded on high-speed video, generating a series of body and leg movement parameters. Of note, FLLIT requires no user input for learning. We used FLLIT to characterise fly models of Parkinson’s Disease (PD) and Spinocerebellar ataxia 3 (SCA3). Between these models, walking gait and tremor characteristics differed markedly, and recapitulated signatures of the respective human diseases. Selective expression of mutant SCA3 in dopaminergic neurons led to phenotypes resembling that of PD flies, suggesting that the behavioural phenotype may depend on the circuits affected, rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits are affected. Almost 190,000 video frames were tracked in this study, allowing, for the first time, high-throughput analysis of gait and tremor features inDrosophilamutants. As an efficient assay of mutant gait and tremor features in an important model system, FLLIT will enable the analysis of the neurogenetic mechanisms that underlie movement disorders.
A systematic review and standardized clinical validity assessment of male infertility genes
Authors: Oud Manon. S. , Volozonoka Ludmila , Smits Roos M. , Vissers Lisenka E.L.M. , Ramos Liliana , Veltman Joris A. 
Published: September 2018

AbstractStudy questionWhich genes are confidently linked to human male infertility?Summary answerOur systematic literature search and clinical validity assessment reveals that a total of 67 genes are currently confidently linked to 81 human male infertility phenotypes.What is known alreadyThe discovery of novel male infertility genes is rapidly accelerating with the availability of Next-Generation Sequencing methods, but the quality of evidence for gene-disease relationships varies greatly. In order to improve genetic research, diagnostics and counseling, there is a need for an evidence-based overview of the currently known genes.Study design, size, durationWe performed a systematic literature search and evidence assessment for all publications in Pubmed until June 2018 covering genetic causes of male infertility and/or defective male genitourinary development.Participants/materials, setting, methodsTwo independent reviewers conducted the literature search and included papers on the monogenic causes of human male infertility and excluded papers on genetic association or risk factors, karyotype anomalies and/or copy number variations affecting multiple genes. Next, the quality and the extent of all evidence supporting selected genes was weighed by a standardized scoring method and used to determine the clinical validity of each gene-disease relationship as expressed by the following six categories: no evidence, limited, moderate, strong, definitive or unable to classify.Main results and the role of chanceFrom a total of 23,031 records, we included 1,286 publications about monogenic causes of male infertility leading to a list of 471 gene-disease relationships. The clinical validity of these gene-disease relationships varied widely and ranged from definitive (n=36) to strong (n=12), moderate (n=33), limited (n=86) or no evidence (n=154). A total of 150 gene-disease relationships could not be classified.Limitations, reasons for cautionOur literature search was limited to Pubmed.Wider implications of the findingsThe comprehensive overview will aid researchers and clinicians in the field to establish gene lists for diagnostic screening using validated gene-disease criteria and identify gaps in our knowledge of male infertility. For future studies, the authors discuss the relevant and important international guidelines regarding research related to gene discovery and provide specific recommendations to the field of male infertility.Study funding/competing interest(s)This work was supported by a VICI grant from The Netherlands Organisation for Scientific Research (918-15-667 to JAV).
Collection of continuous rotation MicroED Data from Ion Beam Milled Crystals of Any Size
Authors: Martynowycz Michael W. , Zhao Wei , Hattne Johan , Jensen Grant J. , Gonen Tamir 
Published: September 2018

AbstractMicrocrystal electron diffraction (MicroED) allows for macromolecular structure solution from nanocrystals. To create crystals of suitable size for MicroED data collection, sample preparation typically involves sonication or pipetting a slurry of crystals from a crystallization drop. The resultant crystal fragments are fragile and the quality of the data that can be obtained from them is sensitive to subsequent sample preparation for cryoEM as interactions in the water-air interface can damage crystals during blotting. Here, we demonstrate the use of a focused ion beam to generate lamellae of macromolecular protein crystals for continuous rotation MicroED that are of ideal thickness, easy to locate, and require no blotting optimization. In this manner, crystals of nearly any size may be scooped and milled to ideal dimensions prior to data collection, thus streamlining the methodology for sample preparation for MicroED.
Propagation of orientation selectivity in a spiking network model of layered primary visual cortex
Authors: Merkt Benjamin , Schüßler Friedrich , Rotter Stefan 
Published: September 2018

AbstractNeurons in different layers of sensory cortex generally have different functional properties. But what determines firing rates and tuning properties of neurons in different layers? Orientation selectivity in primary visual cortex (V1) is an interesting case to study these questions. Thalamic projections essentially determine the preferred orientation of neurons that receive direct input. But how is this tuning propagated though layers, and how can selective responses emerge in layers that do not have direct access to the thalamus? Here we combine numerical simulations with mathematical analyses to address this problem. We find that a large-scale network, which just accounts for experimentally measured layer and cell-type specific connection probabilities, yields firing rates and orientation selectivities matching electrophysiological recordings in rodent V1 surprisingly well. Further analysis, however, is complicated by the fact that neuronal responses emerge in a dynamic fashion and cannot be directly inferred from static neuroanatomy, as some connections tend to have unintuitive effects due to recurrent interactions and strong feedback loops. These emergent phenomena can be understood by linearizing and coarse-graining. In fact, we were able to derive a low-dimensional linear dynamical system effectively describing stimulus-driven activity layer by layer. This low-dimensional system explains layer-specific firing rates and orientation tuning by accounting for the different gain factors of the aggregate system. Our theory can also be used to design novel optogenetic stimulation experiments, thus facilitating further exploration of the interplay between connectivity and function.Author summaryUnderstanding the precise roles of neuronal sub-populations in shaping the activity of networks is a fundamental objective of neuroscience research. In complex neuronal network structures like the neocortex, the relation between the connec-tome and the algorithm implemented in it is often not self-explaining. To this end, our work makes three important contributions. First, we show that the connectivity extracted by anatomical and physiological experiments in visual cortex suffices to explain important properties of the various sub-populations, including their selectivity to visual stimulation. Second, we introduce a novel system-level approach for the analysis of input-output relations of recurrent networks, which leads to the observed activity patterns. Third, we present a method for the design of future optogenetic experiments that can be used to devise specific stimuli resulting in a predictable change of neuronal activity. In summary, we introduce a novel frame-work to determine the relevant features of neuronal microcircuit function that can be applied to a wide range of neuronal systems.
An assessment of the interactions between climatic conditions and genetic characteristic on the agricultural performance of soybeans grown in Northeast Asia
Authors: Park Myoung Ryoul , Cai Chunmei , Seo Min-Jung , Yun Hong-Tae , Park Soo-Kwon , Choi Man-Soo , Park Chang-Hwan , Moon Jung Kyung 
Published: September 2018

AbstractGlycine max, commonly known as soybean or soya bean, is a species of legume native to East Asia. The interactions between climatic conditions and genetic characteristic affect the agricultural performance of soybean. Therefore, an investigation to identify the main elements affecting the agricultural performances of 11 soybeans was conducted in Northeast Asia, China [Harbin (45°12′N) Yanji (42°53′N) Dalian (39°30′N) Qingdao (36°26′N)] Republic of Korea [Suwon (37°16′N) and Jeonju (35°49′N)]. The days to flowering (DTF) of soybeans with the e1-nf and e1-as alleles and the E1e2e3e4 genotype, except Keumgangkong, Tawonkong, and Duyoukong, was relatively short compared to soybeans with other alleles. Although DTF of the soybeans was highly correlated to all climatic conditions, days to maturity (DTM) and 100-seed weight (HSW) of the soybeans showed no significant correlation with any climatic conditions. The soybeans with a dominant Dt1 allele, except Tawonkong, had the longest stem length (STL). Moreover, the STL of the soybeans grown at the test fields showed a positive correlation with only day length (DL) although the results of our chamber test showed that STL of soybean was positively affected by average temperature (AVT) and DL. Soybean yield (YLD) showed positive correlations with latitude and DL (except L62-667, OT89-5, and OT89-6) although the response of YLD to the climatic conditions was cultivar-specific. Our results show that DTF and STL of soybeans grown in Northeast Asia are highly affected by DL although AVT and genetic characteristic also affect DTF and STL. Along with these results, we confirmed that the DTM, HSW, and YLD of the soybeans vary in relation to their genetic characteristic.
Rational Design of Peptide Vaccines for the Highly Lethal Nipah and Hendra Viruses
Authors: Dey Sumanta , Roy Proyasha , Dutta Tathagata , Nandy Ashesh , Basak Subhash C 
Published: September 2018

AbstractThe Nipah virus disease is a lethal infection that has led to 40% to 75% fatalities in Malaysia, Bangladesh and India. The reports of human-to-human transmission documented in Bangladesh has raised the specter of pandemic potential and has caused the World Health Organization to list the Nipah virus as one of the pathogens to be considered for development of drugs and vaccines on urgent basis, neither of which exist against the Nipah virus as of now, although many proposals have been made and trials initiated. Given that there are established country-specific differences in the virus’ effects and fatalities, meeting the sudden need for a vaccine in case of an epidemic will require design, development and preparation for a peptide vaccine. Thus, we propose a protocol for creating peptide vaccines that can be tailor-made for these specific countries, an approach which is being advocated for the first time. Here, we analyze the surface proteins, Fusion protein and Glycoprotein, of the strains currently affecting the three countries on a large scale and determine the specific country-based epitope differences.
A Fully Automated, Faster Noise Reduction Approach to Increasing the Analytical Capability of Chemical Imaging for Digital Histopathology
Authors: Gupta Soumyajit , Mittal Shachi , Kajdacsy-Balla Andre , Bhargava Rohit , Bajaj Chandrajit 
Published: September 2018

AbstractHigh dimensional data, for example from infrared spectral imaging, involves an inherent trade-off in the acquisition time and quality of spatial-spectral data. Minimum Noise Fraction (MNF) developed by Green et al. [1] has been extensively studied as an algorithm for noise removal in HSI (Hyper-Spectral Imaging) data. However, there is a speed-accuracy trade-off in the process of manually deciding the relevant bands in the MNF space, which by current methods could become a person month time for analyzing an entire TMA (Tissue Micro Array). We propose three approaches termed ‘Fast MNF’, ‘Approx MNF’ and ‘Rand MNF’ where the computational time of the algorithm is reduced, as well as the entire process of band selection is fully automated. This automated approach is shown to perform at the same level of reconstruction accuracy as MNF with large speedup factors, resulting in the same task to be accomplished in hours. The different approximations of the algorithm, show the reconstruction accuracy vs storage (50×) and runtime speed (60×) trade-off. We apply the approach for automating the denoising of different tissue histology samples, in which the accuracy of classification (differentiating between the different histologic and pathologic classes) strongly depends on the SNR (signal to noise ratio) of recovered data. Therefore, we also compare the effect of the proposed denoising algorithms on classification accuracy. Since denoising HSI data is done without any ground truth, we also use a metric that assesses the quality of denoising in the image domain between the noisy and denoised image in absence of ground truth.
Colloidal quantum dots suitability for long term cell imaging
Authors: Farias Patricia M. A. , Galembeck André , Milani Raquel , Mendonca Wilson S. , Stingl Andreas 
Published: September 2018

AbstractFluorescent semiconductor nanoparticles in tree-dimensional quantum confinement, quantum dots (QDs), synthesized in aqueous medium, and functionalized with polyethylene glycol, were used as probes for the long-term imaging of glial cells. In vitro living healthy as well as cancer glial cells were labelled by direct insertion of a small volume of QDs contained in aqueous suspension into the culture wells. A long-term monitoring (over 7 days) of the cells was performed and no evidence of cell fixation and/or damage was observed. Two control groups, healthy and cancer glial cells, were used to compare cell viability. During the observation period, labelled and non labelled cells presented the same dynamics and no difference was observed regarding cell viability. To our knowledge, this is the first report of the viability of hydrophilic prepared quantum dots without any further surface treatment than the polyethylene-glycol coverage for the long-term imaging of living cells. Further, the study also permitted the observation of two distinct interaction mechanisms between cells and QDs. Healthy glial cells were mainly labelled at their surface, while non-healthy glial cells have shown a high rate in the uptake of QDs.
Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis
Authors: Niemi Natalie M. , Wilson Gary M. , Overmyer Katherine A. , Vögtle F.-Nora , Lohman Danielle C. , Schueler Kathryn L. , Attie Alan D. , Meisinger Chris , Coon Joshua J. , Pagliarini David J. 
Published: September 2018

SUMMARYMitochondrial proteins are replete with phosphorylation; however, the origin, abundance, and functional relevance of these modifications are largely unclear. Nonetheless, mitochondria possess multiple resident phosphatases, suggesting that protein dephosphorylation may be broadly important for mitochondrial activities. To explore this, we deleted the poorly characterized matrix phosphatasePptc7from mice using CRISPR-Cas9 technology. Strikingly,Pptc7−/−mice exhibited marked hypoketotic hypoglycemia, elevated acylcarnitines, and lactic acidosis, and died soon after birth.Pptc7−/−tissues had significantly diminished mitochondrial size and protein content despite normal transcript levels, but consistently elevated phosphorylation on select mitochondrial proteins. These putative Pptc7 substrates include the protein translocase complex subunit Timm50, whose phosphorylation reduced import activity. We further find that phosphorylation in or near the mitochondrial targeting sequences of multiple proteins can disrupt their import rates and matrix processing. Overall, our data define Pptc7 as a protein phosphatase essential for proper mitochondrial function and biogenesis during the extrauterine transition.
A large close relative ofC. elegansis slow-developing but not long-lived
Authors: Woodruff Gavin C. , Johnson Erik , Phillips Patrick C. 
Published: September 2018

AbstractBackgroundVariation in body size is thought to be a major driver of a wide variety of ecological and evolutionary patterns, including changes in development, reproduction, and longevity.Caenorhabditis inopinatais a recently-discovered fig-associated nematode that is unusually large relative to other members of the genus, including the closely related model systemC. elegans. Here we test whether the dramatic increase in body size has led to correlated changes in key life history and developmental parameters within this species.ResultsUsing four developmental milestones,C. inopinatawas found to have a slower rate of development thanC. elegansacross a range of temperatures. Despite this,C. inopinatadid not reveal any differences in adult lifespan fromC. elegansafter accounting for differences in developmental timing and reproductive mode.C. inopinatafecundity was generally lower than that ofC. elegans, but fitness improved under continuous-mating, consistent with sperm-limitation under gonochoristic (male/female) reproduction.C. inopinataalso revealed greater fecundity and viability at higher temperatures.ConclusionConsistent with observations in other ectotherms, slower growth inC. inopinataindicates a potential trade-off between body size and developmental timing, whereas its unchanged lifespan suggests that longevity is largely uncoupled from its increase in body size. Additionally, temperature-dependent patterns of fitness inC. inopinataare consistent with its geographic origins in subtropical Okinawa. Overall, these results underscore the extent to which changes in ecological context and body size can shape life history traits.