bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling semantic composition and semantic association in the left temporal lobe
Authors: Li Jixing , Pylkkänen Liina 
Published: August 2020

AbstractAlthough composing two words into a complex representation (e.g., “coffee cake”) is conceptually different from forming associations between a pair of words (e.g., “coffee, cake”), the brain regions supporting semantic composition have also been implicated for associative encoding. Here, we adopted a two-word magnetoencephalography (MEG) paradigm which varies compositionality (“French/Korean cheese” vs. “France/Korea cheese”) and strength of association (“France/French cheese” vs. “Korea/Korean cheese”) between the two words. We collected MEG data while 42 English speakers (24 females) viewed the two words successively in the scanner, and we applied both univariate regression analyses and multivariate pattern classification to the source estimates of the two words. We show that the left anterior and middle temporal lobe (LATL; LMTL) are distinctively modulated by semantic composition and semantic association. Specifically, the LATL is mostly sensitive to high-association compositional phrases, while the LMTL responds more to low-association compositional phrases. Pattern-based directed connectivity analyses further revealed a continuous information flow from the anterior to the middle temporal region, suggesting that the integration of adjective and noun properties originated earlier in the LATL is consistently delivered to the LMTL when the complex meaning is newly encountered. Taken together, our findings shed light into a functional dissociation within the left temporal lobe for compositional and distributional semantic processing.Significance StatementPrior studies on semantic composition and associative encoding have been conducted independently within the subfields of language and memory, and they typically adopt similar two-word experimental paradigms. However, no direct comparison has been made on the neural substrates of the two processes. The current study relates the two streams of literature, and appeals to audiences in both subfields within cognitive neuroscience. Disentangling the neural computations for semantic composition and association also offers insight into modeling compositional and distributional semantics, which has been the subject of much discussion in Natural Language Processing and cognitive science.
Cleavage Site Specificity for Processing of Farnesylated Prelamin A by the Zinc Metalloprotease ZMPSTE24
Authors: Babatz Timothy D. , Spear Eric D. , Xu Wenxin , Sun Olivia L. , Nie Laiyin , Carpenter Elisabeth P. , Michaelis Susan 
Published: August 2020

AbstractThe integral membrane zinc metalloprotease ZMPSTE24 is important for human health and longevity. ZMPSTE24 performs a key proteolytic step in maturation of prelamin A, the precursor of the nuclear scaffold protein lamin A. Mutations in the genes encoding either prelamin A or ZMPSTE24 that prevent cleavage cause the premature aging disease Hutchinson Gilford Progeria Syndrome (HGPS) and related progeroid disorders. ZMPSTE24 has a novel structure, with seven transmembrane spans that form a large water-filled membrane chamber whose catalytic site faces the chamber interior. Prelamin A is the only known mammalian substrate for ZMPSTE24, however, the basis of this specificity remains unclear. To define the sequence requirements for ZMPSTE24 cleavage, we mutagenized the eight residues flanking the prelamin A scissile bond (TRSY↓LLGN) to all other 19 amino acids, creating a library of 152 variants. We also replaced these eight residues with sequences derived from putative ZMPSTE24 cleavage sites from amphibian, bird, and fish prelamin A. Cleavage of prelamin A variants was assessed using anin vivoyeast assay that provides a sensitive measure of ZMPSTE24 processing efficiency. We found that residues on the C-terminal side of the cleavage site are most sensitive to changes. Consistent with other zinc metalloproteases, including thermolysin, ZMPSTE24 preferred hydrophobic residues at the P1’ position (Leu647), but in addition, showed a similar, albeit muted, pattern at P2’. Our findings begin to define a consensus sequence for ZMPSTE24 that helps to clarify how this physiologically important protease functions and may ultimately lead to identifying additional substrates.
Promoterless Transposon Mutagenesis Drives Solid Cancers via Tumor Suppressor Inactivation
Authors: Aiderus Aziz , Contreras-Sandoval Ana M. , Meshey Amanda L. , Newberg Justin Y. , Ward Jerrold M. , Swing Deborah , Copeland Neal G. , Jenkins Nancy A. , Mann Karen M. , Mann Michael B. 
Published: August 2020

AbstractA central challenge in cancer genomics is the systematic identification of single and cooperating tumor suppressor genes driving cellular transformation and tumor progression in the absence of oncogenic driver mutation(s). Multiplein vitroandin vivogene inactivation screens have enhanced our understanding of the tumor suppressor gene landscape in various cancers. However, these studies are limited to single or combination gene effects, specific organs, or require sensitizing mutations. In this study, we developed and utilized aSleeping Beautytransposon mutagenesis system that functions only as a gene trap to exclusively inactivate tumor suppressor genes. Using whole body transposon mobilization in wild type mice, we observed that cumulative gene inactivation can drive tumorigenesis of solid cancers. We provide a quantitative landscape of the tumor suppressor genes inactivated in these cancers, and show that despite the absence of oncogenic drivers, these genes converge on key biological pathways and processes associated with cancer hallmarks.
Simultaneous smoothing and detection of topological units of genome organization from sparse chromatin contact count matrices with matrix factorization
Authors: Lee Da-Inn , Roy Sushmita 
Published: August 2020

AbstractThe three-dimensional (3D) organization of the genome plays a critical role in gene regulation for diverse normal and disease processes. High-throughput chromosome conformation capture (3C) assays, such as Hi-C, SPRITE, GAM, and HiChIP, have revealed higher-order organizational units such as topologically associating domains (TADs), which can shape the regulatory landscape governing downstream phenotypes. Analysis of high-throughput 3C data depends on the sequencing depth, which directly affects the resolution and the sparsity of the generated 3D contact count map. Identification of TADs remains a significant challenge due to the sensitivity of existing methods to resolution and sparsity. Here we present GRiNCH, a novel matrix-factorization-based approach for simultaneous TAD discovery and smoothing of contact count matrices from high-throughput 3C data. GRiNCH TADs are enriched in known architectural proteins and chromatin modification signals and are stable to the resolution, and sparsity of the input data. GRiNCH smoothing improves the recovery of structure and significant interactions from low-depth datasets. Furthermore, enrichment analysis of 746 transcription factor motifs in GRiNCH TADs from developmental time-course and cell-line Hi-C datasets predicted transcription factors with potentially novel genome organization roles. GRiNCH is a broadly applicable tool for the analysis of high throughput 3C datasets from a variety of platforms including SPRITE and HiChIP to understand 3D genome organization in diverse biological contexts.
The Role of Colony Temperature in the Entrainment of Circadian Rhythms of Honey Bee Foragers
Authors: Giannoni-Guzmán Manuel A. , Rivera Emmanuel , Aleman-Rios Janpierre , Moreno Alexander M. Melendez , Ramos Melina Perez , Pérez-Claudio Eddie , Loubriel Darimar , Moore Darrell , Giray Tugrul , Agosto-Rivera Jose L. 
Published: August 2020

AbstractHoney bees utilize their circadian rhythms to accurately predict the time of day. This ability allows foragers to remember the specific timing of food availability and its location for several days. Previous studies have provided strong evidence toward light/dark cycles being the primary Zeitgeber for honey bees. Work in our laboratory described large individual variation in the endogenous period length of honey bee foragers from the same colony and differences in the endogenous rhythms under different constant temperatures. In this study, we further this work by examining temperature inside the honey bee colony. By placing temperature and light data loggers at different locations inside the colony we measured temperature at various locations within the colony. We observed significant oscillations of temperature inside the hive, that show seasonal patterns. We then simulated the observed temperature oscillations in the laboratory and found that using the temperature cycle as a Zeitgeber, foragers present large individual differences in the phase of locomotor rhythms with respect to temperature. Moreover, foragers successfully synchronize their locomotor rhythms to these simulated temperature cycles. Advancing the cycle by six hours, resulted in changes in the phase of activity in some foragers in the assay. The results shown in this study highlight the importance of temperature as a potential Zeitgeber in the field. Future studies will examine the possible functional and evolutionary role of the observed phase differences of circadian rhythms.
Shift work dynamics and division of labor: honeybee foraging and fanning tasks
Authors: Giannoni-Guzmán Manuel A. , Giray Tugrul , Agosto-Rivera Jose L. 
Published: August 2020

AbstractIn complex societies common social needs such as vigilance, care giving, resource gathering, and production are attended around the clock. In humans, these services are constantly provided using a shift work strategy where different individuals, or groups of individuals perform their tasks at different times of the day. However, shift work strategy in job organization in other social organisms remains unclear. Previous studies in honeybees for two jobs support shift work for only pollen foragers and not for nursing behavior. Here we examined shift work dynamics for three types of jobs performed by honeybee foragers. Specifically, we studied pollen foragers, non-pollen foragers and bees fanning at the entrance of the colony, a job important for orientation and temperature control. Major features of the observed shift work were: 1) individuals can be divided into early and late shifts; 2) there are constant workers; 3) based on job, shift work is performed by fewer or greater number of individuals; 4) shift work of an individual is plastic and may change with age; 5) foraging and fanning shifts are coupled yet dissociable. This study adds to the findings that shift work is not exclusive to modern human societies and that a natural form of shift work exists in honeybees. These results suggest that shift work in honeybees is a feature of worker division of labor. Future studies aiming to further understand the structure, function and mechanism of this natural form of shift work in honey bees not only could have an impact on agriculture but also may provide insight into alternative forms of shift work strategies that may reduce the various health problems associated with shift work in humans.
Vesicle capture by discrete self-assembled clusters of membrane-bound Munc13
Authors: Li Feng , Sundaram Venkat Kalyana , Gatta Alberto T. , Coleman Jeff , Krishnakumar Shyam S. , Pincet Frederic , Rothman James E. 
Published: August 2020

ABSTRACTMunc13 is a large banana-shaped soluble protein that is involved in the regulation of synaptic vesicle docking and fusion. Recent studies suggested that multiple copies of Munc13 form nanoassemblies in active zones of neurons. However, it is not known if such clustering is an inherent self-assembly property of Munc13 or whether Munc13 clusters indirectly by multivalent binding to synaptic vesicles or specific plasma membrane domains at docking sites in the active zone. The functional significance of putative Munc13 clustering is also unknown. Here we report that nano-clustering is an inherent property of Munc13, and is indeed required for vesicle binding to bilayers containing Munc13. Pure Munc13 reconstituted onto supported lipid bilayers assembled into clusters containing from 2 to ∼20 copies as revealed by a combination of quantitative TIRF microscopy and step-wise photobleaching. Surprisingly, only clusters a minimum of 6 copies of Munc13 were capable of efficiently capturing and retaining small unilamellar vesicles. The C-terminal C2C domain of Munc13 is not required for Munc13 clustering, but is required for efficient vesicle capture.
Discovery of a microbially produced small molecule in a host-specific organ
Authors: Zink Katherine E. , Tarnowski Denise A. , Lazzara Phillip R. , Moore Terry W. , Mandel Mark J. , Sanchez Laura M. 
Published: August 2020

AbstractThe lifelong relationship between the Hawaiian bobtail squid,Euprymna scolopes, and its microbial symbiont,Vibrio fischeri, represents a simplified model system for studying microbiome establishment and maintenance. The bacteria colonize a dedicated symbiotic light organ in the squid, from which bacterial luminescence camouflages the hosts in a process termed counterillumination. The squid hosts hatch without their symbionts, which must be acquired from the ocean amid a diversity of non-beneficial bacteria, so precise molecular communication is required for initiation of the specific relationship. It is therefore likely that there may be specialized metabolites used in the light organ microenvironment to modulate these processes. To identify small molecules that may influence the establishment of this symbiosis, we used imaging mass spectrometry to analyze metabolite production inV. fischeriwith altered biofilm production, which correlates directly to colonization capability in its host. ‘Biofilm-Up’ and ‘Biofilm-Down’ mutants were compared to a wild-type strain, and masses that were more abundantly produced by the biofilm-up mutant were detected. Using a combination of structure elucidation and synthetic chemistry, one such signal was determined to be a diketopiperazine, cyclo(d-histidyl-l-proline). This diketopiperazine modulated luminescence inV. fischeriand, using label-free imaging mass spectrometry, was directly detected in the light organ of the colonized host. This work highlights the continued need for untargeted discovery efforts in host-microbe interactions and showcases the benefits of the squid-Vibriosystem for identification and characterization of small molecules that modulate microbiome behaviors.Significance StatementThe complexity of animal microbiomes presents challenges to defining signaling molecules within the microbial consortium and between the microbes and the host. By focusing on the binary symbiosis betweenVibrio fischeriandEuprymna scolopes, we have combined genetic analysis with direct imaging to define and study small molecules in the intact symbiosis. We have detected and characterized a diketopiperazine produced by strong biofilm-formingV. fischeristrains that was detectable in the host symbiotic organ, and which influences bacterial luminescence. Biofilm formation and luminescence are critical for initiation and maintenance of the association, respectively, suggesting that the compound may link early and later development stages, providing further evidence that multiple small molecules are important in establishing these beneficial relationships.
Live-imaging of endothelial Erk activity reveals dynamic and sequential signalling events during regenerative angiogenesis
Authors: Okuda Kazuhide S. , Keyser Mikaela , Gurevich David B. , Sturtzel Caterina , Patterson Scott , Chen Huijun , Scott Mark , Condon Nicholas D. , Martin Paul , Distel Martin , Hogan Benjamin M. 
Published: August 2020

AbstractThe formation of new blood vessel networks occurs via angiogenesis during development, tissue repair and disease. Angiogenesis is regulated by intracellular endothelial signalling pathways, induced downstream of Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). A major challenge in understanding angiogenesis is interpreting how signalling events occur dynamically within endothelial cell populations during sprouting, proliferation and migration. Erk is a central downstream effector of Vegf-signalling and reports the signalling that drives angiogenesis. We generated a vascular Erk biosensor transgenic line in zebrafish using a kinase translocation reporter that allows live-imaging of Erk-signalling dynamics. We demonstrate the utility of this line to live-image Erk activity during physiologically relevant angiogenic events. Further, we reveal dynamic and sequential endothelial cell Erk-signalling events following blood vessel wounding. Initial signalling is dependent upon Ca2+in the earliest responding endothelial cells, but is independent of Vegfr-signalling and local inflammation. The sustained regenerative response however, involves a Vegfr-dependent mechanism that initiates concomitant with the wound inflammatory response. This work thus reveals a highly dynamic sequence in regenerative angiogenesis that was not previously appreciated. Altogether, this study demonstrates the utility of a unique biosensor strain for analysing dynamic endothelial Erk-signalling events and validates a new resource for the study of vascular signalling in real-time.
Measuring DNA mechanics on the genome scale
Authors: Basu Aakash , Bobrovnikov Dmitriy G. , Qureshi Zan , Kayikcioglu Tunc , Ngo Thuy T. M. , Ranjan Anand , Eustermann Sebastian , Cieza Basilio , Morgan Michael T. , Hejna Miroslav , Rube H. Tomas , Hopfner Karl-Peter , Wolberger Cynthia , Song Jun S. , Ha Taekjip 
Published: August 2020

AbstractMechanical deformations of DNA such as bending are ubiquitous and implicated in diverse cellular functions1. However, the lack of high-throughput tools to directly measure the mechanical properties of DNA limits our understanding of whether and how DNA sequences modulate DNA mechanics and associated chromatin transactions genome-wide. We developed an assay called loop-seq to measure the intrinsic cyclizability of DNA – a proxy for DNA bendability – in high throughput. We measured the intrinsic cyclizabilities of 270,806 50 bp DNA fragments that span the entire length ofS. cerevisiaechromosome V and other genomic regions, and also include random sequences. We discovered sequence-encoded regions of unusually low bendability upstream of Transcription Start Sites (TSSs). These regions disfavor the sharp DNA bending required for nucleosome formation and are co-centric with known Nucleosome Depleted Regions (NDRs). We show biochemically that low bendability of linker DNA located about 40 bp away from a nucleosome edge inhibits nucleosome sliding into the linker by the chromatin remodeler INO80. The observation explains how INO80 can create promoter-proximal nucleosomal arrays in the absence of any other factors2by reading the DNA mechanical landscape. We show that chromosome wide, nucleosomes are characterized by high DNA bendability near dyads and low bendability near the linkers. This contrast increases for nucleosomes deeper into gene bodies, suggesting that DNA mechanics plays a previously unappreciated role in organizing nucleosomes far from the TSS, where nucleosome remodelers predominate. Importantly, random substitution of synonymous codons does not preserve this contrast, suggesting that the evolution of codon choice has been impacted by selective pressure to preserve sequence-encoded mechanical modulations along genes. We also provide evidence that transcription through the TSS-proximal nucleosomes is impacted by local DNA mechanics. Overall, this first genome-scale map of DNA mechanics hints at a ‘mechanical code’ with broad functional implications.
The Effect of Task on Object Processing revealed by EEG decoding
Authors: Ken Yip Hoi Ming , Cheung Leo Y. T. , Ngan Vince S. H. , Wong Yetta Kwailing , Wong Alan C.-N. 
Published: August 2020

AbstractRecent studies showed that task demand affects object representations in higher-level visual areas and beyond, but not so much in earlier areas. There are, however, limitations in those studies including the relatively weak manipulation of task due to the use of familiar real-life objects, the low temporal resolution in fMRI, and the emphasis on the amount and not the source of information carried by brain activations. In the current study, observers categorized images of artificial objects in one of two orthogonal dimensions, shape and texture, while their brain activity was recorded with electroencephalogram (EEG). Results showed that object processing along the texture dimension was affected by task demand starting from a relatively late time (320-370ms time window) after image onset. The findings are consistent with the view that task exerts an effect on the later phases of object processing.
Museomics of a rare taxon: placing Whalleyanidae in the Lepidoptera Tree of Life
Authors: Twort Victoria G. , Minet Joël , Wheat Christopher W. , Wahlberg Niklas 
Published: August 2020

AbstractMuseomics is a valuable tool that utilises the diverse biobanks that are natural history museums. The ability to sequence genomes from old specimens has expanded not only the variety of interesting taxa available to study but also the scope of questions that can be investigated in order to further knowledge about biodiversity. Here we present whole genome sequencing results from the enigmatic genus Whalleyana, as well as the families Callidulidae and Hyblaeidae. Library preparation was carried out on four museum specimens and one existing DNA extract and sequenced with Illumina short reads. De novo assembly resulted in highly fragmented genomes with the N50 ranging from 317 – 2,078 bp. Mining of a manually curated gene set of 332 genes from these draft genomes had an overall gene recovery rate of 64 – 90%. Phylogenetic analysis places Whalleyana as sister to Callidulidae, and Hyblaea as sister to Pyraloidea. Since the former sister-group relationship turns out to be also supported by ten morphological synapomorphies, we propose to formally assign the Whalleyanidae to the superfamily Calliduloidea. These results highlight the usefulness of not only museum specimens, but also existing DNA extracts, for whole genome sequencing and gene mining for phylogenomic studies.
Applying genomic data to seagrass conservation
Authors: Phair Nikki L , Nielsen Erica S , von der Heyden Sophie 
Published: August 2020

AbstractAlthough genomic diversity is increasingly recognised as a key component of biodiversity, it is seldom used to inform conservation planning. Estuaries and keystone species such as the southern African seagrass,Zostera capensis, are under severe anthropogenic pressure and are often poorly protected. In this study we integrated SNP data generated from populations ofZ. capensisacross the South African coastline into the spatial prioritisation tool Marxan. We included different measures of genomic variation to account for genomic diversity, distinctness and evolutionary potential to explore spatial planning scenarios. We investigated how conservation priority areas identified by targeting only habitat type, differed from those identified by also including genomic measures; further we assessed how different genetic diversity metrics change prioritisation outcomes. All scenarios targeting genomic variation identified unique conservation prioritisation areas compared to scenarios only targeting habitat type. As such, omitting these estuaries from regional MPA networks risks the loss of evolutionarily important populations, threatening resilience and persistence of associated estuarine communities and their ecosystem services. We also observed a high degree of overlap between prioritisation outcomes across targeted measures of genomic variation. As such, by including even single measures of genomic variation, it may be possible to sufficiently represent the evolutionary processes behind the patterns of variation, while simplifying the conservation prioritisation procedure.