bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unperturbed dormancy recording reveals stochastic awakening strategies in endocrine treated breast cancer cells
Authors: Rosano Dalia , Sofyali Emre , Dhiman Heena , Ivanoiu Diana , Slaven Neil , Hong Sung Pil , Rocca Andrea , Bravaccini Sara , Ravaioli Sara , Noberini Roberta , Bonaldi Tiziana , Magnani Luca 
Published: April 2021

AbstractHormone dependent breast cancer (HDBC) is the most commonly diagnosed tumor type in women. Adjuvant endocrine therapies (ET) have been the cornerstone in the clinical management of HDBC patients for over forty years. A vast proportion of HDBC patients incur long periods of clinical dormancy following ET, with tumour awakening appearing at a steady pace for up to 25 years (Pan et al., 2017). Extensive genomic studies have demonstrated that 15-30% of clinical relapses develop recurrent genomic changes which contribute to drug resistance (i.e. ESR1 activating mutations) (Bertucci et al., 2019; Magnani et al., 2017; Razavi et al., 2018). However, even in these cases, there is no conclusive evidence around the pre-existence vs.de novonature of these events. We previously showed that ETs can trigger and select for dormancy in subpopulations of breast cancer (Hong et al., 2019). In this work we took two novel approaches to investigate the dormancy and awakening roadmap of HDBC cells at unprecedented detail. Firstly, we leveraged a rare cohort of n=5 patients which were treated with primary adjuvant ETs in the absence of surgery (TRACING-HT) to dissect the contribution of genomic aberrations to tumor awakening. Next, we developed a first of its kind evolutionary studyin vitroto systematically annotate cancer cells adaptive strategies at single cell level in unperturbed systems during a period of several months (TRADITIOM). Collectively our data suggest that ETs steer HDBC cells into an inherently unstable dormant state. Over time, routes to awakening emerge sporadically and spontaneously in single lineages. Each dormant cell retains an intrinsic awakening probability which we propose is a function of epigenetic decay. Awakening occurs without an external trigger and involves multiple apparent endpoint phenotypes that cannot be fully explained by conventional Darwinian genetic selection processes. Finally, our data show that common genetic hits associated with resistance happen downstream of awakening. Overall, our data have uncovered previously unsuspected roles for stochastic nongenetic events during dormancy with profound clinical implications.
A ‘Variant Viewer’ for investigating population-level variation inArabidopsis thaliana
Authors: Cumming Matthew , Esteban Eddi , Lau Vincent , Pasha Asher , Provart Nicholas J. 
Published: April 2021

AbstractHigh throughput sequencing has opened the doors for investigators to probe genetic variation present in large populations of organisms. In plants, the 1001 Genomes Project (1001genomes.org) is one such effort that sought to characterize the extant worldwide variation inArabidopsis thalianafor future analyses to compare and draw upon. We developed a web application that accesses the 1001 Genomes database called The Variant Viewer, for investigators to view variants in anyA. thalianagene and within gene families. These variants may be visualized in the context of alignments of queried genes, across splice isoforms of these genes and in relation to conserved domains.
Informational masking vs. crowding — A mid-level trade-off between auditory and visual processing
Authors: Zhang Min , Denison Rachel N , Pelli Denis G , Le Thuy Tien C , Ihlefeld Antje 
Published: April 2021

AbstractIn noisy or cluttered environments, sensory cortical mechanisms help combine auditory or visual features into perceived objects. Knowing that individuals vary greatly in their ability to suppress unwanted sensory information, and knowing that the sizes of auditory and visual cortical regions are correlated, we wondered whether there might be a corresponding relation between an individual’s ability to suppress auditory vs. visual interference. Inauditory masking, background sound makes spoken words unrecognizable. When masking arises due to interference at central auditory processing stages, beyond the cochlea, it is calledinformationalmasking (IM). A strikingly similar phenomenon in vision, calledvisual crowding, occurs when nearby clutter makes a target object unrecognizable, despite being resolved at the retina. We here compare susceptibilities to auditory IM and visual crowding in the same participants. Surprisingly, across participants, we find a negative correlation (R= −0.7) between IM susceptibility and crowding susceptibility: Participants who have low susceptibility to IM tend to have high susceptibility to crowding, and vice versa. This reveals a mid-level trade-off between auditory and visual processing.
Optical Probing of Local Membrane Potential with Fluorescent Polystyrene Beads
Authors: Shapira Zehavit , Degani-Katzav Nurit , Yudovich Shimon , Grupi Asaf , Weiss Shimon 
Published: April 2021

AbstractStudying the electrical activity in single cells and in local circuits of excitable cells, like neurons, requires an easy to use and high throughput methodology that enables the measurement of membrane potential. Studying the electrical properties in particular sub-compartments of neurons, or in a specific type of neurons produces additional complexity. An optical voltage-imaging technique that allows high spatial and temporal resolution could be an ideal solution. However, most of the valid voltage imaging techniques are nonspecific; The ones that are more site-directed require much pre-work and specific adaptations in addition to other disadvantages. Here, a new technique for membrane voltage imaging, based on FRET between fluorescent polystyrene (FPS) beads and Dipicrylamine (DPA) is explored. Not only fluorescent intensity is demonstrated to be correlated with membrane potential, but more importantly, single particle voltage detection is demonstrated. Among other advantages, FPS beads can be synthesized with functional surface groups, and be further targeted to specific proteins via conjugation of recognition molecules. Therefore, FPS beads, in the presence of DPA, constitute single-particle detectors for membrane voltage, with a potential to be localized to specific membrane compartments. This new and accessible platform for targeted optical voltage imaging may further elucidate the mechanisms of neuronal electrical activity.
Point-localized and site-specific membrane potential optical recording by engineered single fluorescent nanodiscs
Authors: Grupi Asaf , Shapira Zehavit , Degani-Katzav Nurit , Yudovich Shimon , Weiss Shimon 
Published: April 2021

AbstractNanodisc technology was implemented as a platform for voltage nanosensors. A FRET-based voltage sensing scheme employing fluorescent nanodiscs and the hydrophobic ion dipicrylamine (DPA) was developed and utilized to optically record membrane potentials on the single nanodisc level. Ensemble- and single- nanosensor recordings were demonstrated for HEK293 cells and primary cortical neuron cells. Conjugation of nanodiscs to anti-GABA-A antibodies allowed for site specific membrane potential measurements from post synaptic sites.
A neural circuit for wind-guided olfactory navigation
Authors: Matheson Andrew M.M. , Lanz Aaron J. , Medina Ashley M. , Licata Al M. , Currier Timothy A. , Syed Mubarak H. , Nagel Katherine I. 
Published: April 2021

AbstractTo navigate towards a food source, animals must frequently combine odor cues that tell them what sources are useful with wind direction cues that tell them where the source can be found. Where and how these two cues are integrated to support navigation is unclear. Here we identify a pathway to the Drosophila fan-shaped body (FB) that encodes attractive odor and promotes upwind navigation. We show that neurons throughout this pathway encode odor, but not wind direction. Using connectomics, we identify FB local neurons called hΔC that receive input from this odor pathway and a previously described wind pathway. We show that hΔC neurons exhibit odor-gated, wind direction-tuned activity, that sparse activation of hΔC neurons promotes navigation in a reproducible direction, and that hΔC activity is required for persistent upwind orientation during odor. Based on connectome data, we develop a computational model showing how hΔC activity can promote navigation towards a goal such as an upwind odor source. Our results suggest that odor and wind cues are processed by separate pathways and integrated within the FB to support goal-directed navigation.
Pre-existing chromatin accessibility and gene expression differences among naïve CD4+T cells influence effector potential
Authors: Rogers Dakota , Sood Aditi , Wang HanChen , van Beek Jasper J. P. , Rademaker Thomas J. , Artusa Patricio , Schneider Caitlin , Shen Connie , Wong Dylan C. , Lebel Marie-Ève , Condotta Stephanie A. , Richer Martin J. , Martins Andrew J. , Tsang John S. , Barreiro Luis , Francois Paul , Langlais David , Melichar Heather J. , Textor Johannes , Mandl Judith N. 
Published: April 2021

SummaryCD4+T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probed the heterogeneity present among naïve CD4+T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and epigenetic differences. Using single-cell RNA sequencing, we showed that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a read-out of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naïve CD4+T cells impact follicular helper cell (TFH) versus non-TFHeffector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naïve CD4 T cell chromatin landscapes that ultimately shape their effector potential.
Nrf2 modulates the hybrid epithelial/mesenchymal phenotype and Notch signaling during collective cancer migration
Authors: Vilchez Mercedes Samuel A , Bocci Federico , Zhu Ninghao , Levine Herbert , Onuchic José N , Jolly Mohit Kumar , Wong Pak Kin 
Published: April 2021

AbstractHybrid epithelial/mesenchymal cells (E/M) are key players in aggressive cancer metastasis. It remains a challenge to understand how these cell states, which are mostly non-existent in healthy tissue, become stable phenotypes participating in collective cancer migration. The transcription factor Nrf2, which is associated with tumor progression and resistance to therapy, appears to be central to this process. Here, using a combination of single cell biosensors, immunocytochemistry, and computational modeling, we show that Nrf2 functions as a phenotypic stability factor for hybrid E/M cells by inhibiting a complete epithelial-mesenchymal transition (EMT) during collective cancer migration. We also demonstrate that Nrf2 and EMT signaling are spatially coordinated near the migrating front. In particular, computational analysis of an Nrf2-EMT-Notch network and experimental modulation of Nrf2 by pharmacological treatment or CRISPR/Cas9 gene editing reveal that Nrf2 stabilizes a hybrid E/M phenotype which is maximally observed in the interior region immediately behind the leading edge. We further demonstrate that the Nrf2-EMT-Notch network enhances Dll4 and Jagged1 expression near the leading edge, which correlates with the formation of leader cells and protruding tips. Altogether, our results provide direct evidence that Nrf2 acts as a phenotypic stability factor in restricting complete EMT and plays an important role in coordinating collective cancer migration.
Multi-state structure determination and dynamics analysis reveals a new ubiquitin-recognition mechanism in yeast ubiquitin C-terminal hydrolase
Authors: Okada Mayu , Tateishi Yutaka , Nojiri Eri , Mikawa Tsutomu , Rajesh Sundaresan , Ogasa Hiroki , Ueda Takumi , Yagi Hiromasa , Kohno Toshiyuki , Kigawa Takanori , Shimada Ichio , Güntert Peter , Ito Yutaka , Ikeya Teppei 
Published: April 2021

AbstractDespite accumulating evidence that protein dynamics is indispensable for understanding the structural basis of biological activities, it remains challenging to visualize the spatial description of the dynamics and to associate transient conformations with their molecular functions. We have developed a new NMR protein structure determination method for the inference of multi-state conformations using multiple types of NMR data, including paramagnetic NMR and residual dipolar couplings, as well as conventional NOEs. Integration of these data in the structure calculation permits delineating accurate ensemble structures of biomacromolecules. Applying the method to the protein yeast ubiquitin hydrolase 1 (YUH1), we find large dynamics of its N-terminus and crossover loop surrounding the active site for ubiquitin-recognition and proteolysis. The N-terminus gets into and out of the crossover loop, suggesting their underlying functional significance. Our results, including those from biochemical analysis, show that large motion surrounding the active site contributes strongly to the efficiency of the enzymatic activity.
A facilitation between large herbivores and ants accelerates litter decomposition by modifying soil microenvironmental conditions
Authors: Li Xiaofei , Risch Anita C. , Sanders Dirk , Liu Guofang , Prather Chelse , Wang Zhongnan , Hassan Nazim , Gao Qiang , Wang Deli , Zhong Zhiwei 
Published: April 2021

AbstractLarge herbivores and insects commonly coexist and play important functional roles in grassland ecosystems. The interactive effects of these two animal groups in shaping ecosystem processes and functioning are poorly understood. In a semi‐arid grassland of northeastern China, we previously found a reciprocal facilitation between large herbivores (cattle;Bos tarurs) and ants: cattle grazing led to a twofold increase in ant mound abundance compared with ungrazed sites, while the presence of ant mounds, in turn, increased the foraging of cattle during the peak of the growing season.Here, by using a large‐scale, 4‐year (2010–2013) manipulative experiment, we further investigated how such a facilitation between large herbivores and ants can affect a key ecosystem process, litter decomposition. Using a set of small‐scale reciprocal translocation litterbag experiments, we separated the effects of litter quality and soil microenvironmental factors altered by cattle and ants on litter decomposition rates.A significant interaction between the experimental factors, cattle grazing and ant presence, showed that litter decomposition rate was at the highest levels when both cattle and ants were present, with only a small impact when each was present on its own. Mechanistically, cattle and ants exerted limited effects on litter quality (litter C:N ratio). However, these animals greatly altered soil microenvironments by increasing soil N availability, which in turn increased soil microbial biomass and accelerated decomposition process.Synthesis. Our results demonstrate how positive interactions between two groups of animals, large herbivores and ants, can affect decomposition rates, with important consequences for ecosystem carbon and nutrient cycling. Large herbivores, either domestic or wild, often coexist and interact frequently with a diverse of other fauna in terrestrial ecosystems. Assessing their interactive effects will help us to better understand their role in shaping ecosystem processes and functioning with important management implications.A freePlain Language Summarycan be found within the Supporting Information of this article.
Respiratory temperature responses of tropical conifers differ with leaf morphology
Authors: Schmiege Stephanie C. , Buckley Brendan M. , Stevenson Dennis W. , Heskel Mary A. , Cuong Truong Quang , Nam Le Canh , Griffin Kevin L. 
Published: April 2021

Abstract

Photosynthetic traits suggest that shade tolerance may explain the contrasting success of two conifer taxa, Podocarpaceae and Pinaceae, in tropical forests. Needle‐leaved species from Pinus (Pinaceae) are generally absent from tropical forests, whereas Pinus krempfii, a flat‐leaved pine, and numerous flat‐leaved Podocarpaceae are abundant. Respiration (R) traits may provide additional insight into the drivers of the contrasting success of needle‐ and flat‐leaved conifers in tropical forests.

We measured the short‐term respiratory temperature (RT) response between 10 and 50°C and foliar morphological traits of three needle‐ and seven flat‐leaved conifer species coexisting in a tropical montane forest in the Central Highlands of Vietnam containing notable conifer diversity. We fit a lognormal polynomial model to each RT curve and extracted the following three parameters: a (basal R), and b and c (together describing the shape of the response).

Needle‐leaved species (Pinus kesiya, Pinus dalatensis and Dacrydium elatum) had higher rates of area‐based R at 25°C (R25‐area) as well as higher area‐based modelled basal respiration (a) than flat‐leaved species (P. krempfii, Podocarpus neriifolius, Dacrycarpus imbricatus, Nageia nana, Taxus wallichiana, Keteeleria evelyniana and Fokienia hodginsii). No significant differences were found between needle‐ and flat‐leaved species in mass‐based R25 (R25‐mass) or in the shape of the RT response (b and c); however, interspecific differences in R25‐mass, R at nighttime temperature extremes (R4.1 and R20.6) and leaf traits were apparent.

Differences in R25‐area and a suggest that needle‐leaved foliage may be more energetically costly to maintain than flat‐leaved foliage, providing new insight and additional support for the hypothesis that shade tolerance is an important driver of Podocarpaceae success and Pinaceae absence in the majority of tropical forests.

Interspecific differences in R25‐mass and leaf traits highlight that varying ecological strategies are employed by conifers to coexist and survive in the Central Highlands of Vietnam. Ultimately, these data further our understanding of current conifer biogeographical distributions and underscore the need for additional studies to elucidate the effects of extreme temperature events on the continued survival of conifers in this unique forest.

A free Plain Language Summary can be found within the Supporting Information of this article.
Disentangling the social complexities of assisted migration through deliberative methods
Authors: Hagerman Shannon , Kozak Robert 
Published: April 2021

AbstractThe impacts of climate change have prompted forest practitioners and decision makers to consider assisted migration (a form of plant translocation) as a management strategy.Historically, decisions around forest management, including the application of novel approaches, have been driven by the interests of particular groups and informed by a narrow range of knowledge inputs.Drawing on our program of social science research and that of others, we demonstrate: (a) the need to expand the range of groups consulted in climate‐adaptive forest management; (b) the necessity to incorporate a broader range of knowledge inputs; and (c) the development and application of deliberative approaches that facilitate both.Synthesis. We identify a novel deliberative agenda for understanding the societal aspects and implications of plant translocation research and practice, and make recommendations for mixed socially based research methods that revolve around engaging a diverse set of publics and forms of knowledge in environmental decision‐making and policy‐setting.
High tree diversity enhances light interception in tropical forests
Authors: Duarte Marina Melo , Moral Rafael de Andrade , Guillemot Joannès , Zuim Caroline Isaac Ferreira , Potvin Catherine , Bonat Wagner Hugo , Stape José Luiz , Brancalion Pedro H. S. 
Published: April 2021

Abstract

Understanding the processes that underlie the effects of tree diversity on primary production is of foremost importance to enhance climate change mitigation by tropical forests. Here, we investigated the effects of tree diversity on light interception over space and time in two tropical tree experiments, located in Panama—Sardinilla site (monocultures to 18‐species mixtures), and in Brazil—Anhembi site (20‐ to 114‐species mixtures).

We assessed intercepted photosynthetically active radiation (iPAR) over horizontal grids and vertical transects (up to 5 m high in Sardinilla and up to 4 m high in Anhembi), in plots containing different richness levels and combinations of species.

Light interception increased from monocultures to 5‐species mixtures in Sardinilla and from 20‐ to 114‐species mixtures in Anhembi (during the dry season). At the Sardinilla site, five‐species mixtures showed iPAR comparable to the best performing monocultures, despite substantial differences observed among monocultures. Diversity‐iPAR relationships changed seasonally and were more pronounced during the dry season. Tree richness promoted a less variable temporal and spatial (i.e. both horizontal and vertical) distribution of light interception.

Synthesis. High tree diversity (i.e. over a hundred species in mixture) maximizes the amount of light intercepted by the canopy in restored tropical forests through more even capture in space and time. Diversity‐light interception relationships should be critically considered for designing cost‐efficient large‐scale tropical forest restoration programs.
The ‘Hiroshima Maidens’ on Different Shores: Decentralising Scarred Japanese Femininity in the A‐Bomb Victimhood
Authors: Wake Naoko 
Published: April 2021

AbstractThis article explores uneven histories of hibakusha (survivors of Hiroshima and Nagasaki atomic bombings in 1945) activism involving publicly visible nuclear injuries. By looking beyond the famous ‘Hiroshima Maidens’ and expanding an intersectional analysis of gender, race and disability to Korean, Japanese and American hibakusha, this article decentralises the scarred Japanese femininity in our understanding of hibakusha history. As Japan's former colonial subjects, Korean hibakusha successfully obtained disability compensation from the Japanese government beginning in the 1970s, helping Japanese and American survivors, too, to gain better treatment by the government. By contrast, US survivors remained unrecognised by any official US entities, despite the rising activism in Asian America in the 1970s. This article argues, it was a redefined, postcolonial masculinity of Korean and Japanese hibakusha that brought them tangible state benefits. In America, transforming gender was not enough to deconstruct the ‘model minority’ myth, which trivialised any physical injuries and disabilities among Asian Americans as self‐healable. Indeed, racism might have overwhelmed gender by making both femininity and masculinity irrelevant to racial minority rights. This illuminates a need to analyse the intersection of gender, race and disability in trans‐Pacific contexts so as to better identify the roots of nuclear injustice.