bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell carbon and nitrogen incorporation and remineralization profiles are uncoupled from phylogenetic groupings of diatom-associated bacteria
Authors: Mayali Xavier , Samo Ty , Kimbrel Jeff , Stuart Rhona K. , Morris Megan , Rolison Kristina , Ramon Christina , Kim Young-Mo , Munoz-Munoz Nathalie , Nicora Carrie , Purvine Sam , Lipton Mary , Weber Peter K. 
Published: July 2022

AbstractBacterial remineralization of algal organic matter is thought to fuel algal growth, but this has not been quantified. Consequently, we cannot currently predict whether some bacterial taxa may provide more remineralized nutrients to algae than others, nor whether this is linked their incorporation. We quantified bacterial incorporation of algal-derived complex dissolved organic C (DOC) and N (DON) and net algal incorporation of remineralized C and N at the single cell level using isotope tracing and NanoSIMS for fifteen bacterial co-cultures growing with the diatom Phaeodactylum tricornutum. We found unexpected variability in the net C and N fluxes between algae and bacteria, including non-ubiquitous complex DON utilization and remineralization. We identified three distinct functional categories of metabolic interactions, which we termed macromolecule remineralizers, macromolecule users, and small-molecule users, the latter exhibiting efficient growth under low carbon availability. The functional categories were not linked to phylogeny and could not be elucidated strictly from metabolic capacity as predicted by comparative genomics. Using comparative proteogenomic analyses, we show that a complex DON incorporating strain expressed proteins related to growth and peptide transport, and a non-incorporator prioritized reactive oxygen species scavenging and inorganic nutrient uptake. Our analysis suggests that phylogeny does not predict the extent of algae-bacteria metabolite exchange, and activity-based measurements are indispensable to classify the high diversity of microbes into functional groups. These categorizations are useful for conceptual understanding and mechanistic numerical modeling to ultimately predict the fate of elemental cycles in response to environmental change.
Early Electrophysiological Aberrations in the Hippocampus of the TgF344-AD Rat Model as a Potential Biomarker for Alzheimer’s Disease Prognosis
Authors: Moradi Faraz , van den Berg Monica , Mirjebreili Morteza , Kosten Lauren , Verhoye Marleen , Amiri Mahmood , Keliris Georgios A. 
Published: July 2022

AbstractThe hippocampus is thought to guide navigation and has an essential contribution to learning and memory. Hippocampus is one of the brain regions impaired in Alzheimer’s disease (AD), a neurodegenerative disease with progressive memory impairments and cognitive decline. Although successful treatments for AD are still not available, developing new strategies to detect AD at early stages before clinical manifestation is crucial for timely interventions. Here, we investigated in the TgF344-AD rat model the classification of AD-transgenic rats versus Wild-type littermates (WT) from electrophysiological activity recorded in the hippocampus of freely moving subjects at an early, pre-symptomatic stage of the disease (6 months old). To this end, recorded signals were filtered in two separate frequency regimes namely low frequency LFP signals and high frequency spiking activity and passed to machine learning (ML) classifiers to identify the genotype of the rats (TG vs. WT). For the low frequency analysis, we first filtered the signals and extracted the power spectra in different frequency bands known to carry differential information in the hippocampus (delta, theta, slow- and fast-gamma) while for the high frequency analysis, we extracted spike-trains of neurons and calculated different distance metrics between them, including Van Rossum (VR), Inter Spike Interval (ISI), and Event Synchronization (ES). These measures were then used as features for classification with different ML classifiers. We found that both low and high frequency signals were able to classify the rat genotype with a high accuracy with specific signals such as the gamma band power, providing an important fraction of information. In addition, when we combined information from both low and high frequency the classification was boosted indicating that independent information is present across the two bands. The results of this study offer a better insight into how different regions of the hippocampus are affected in earlier stages of AD.
α1 adrenergic receptor - PKC - Pyk2 - Src signaling boosts L-type Ca2+ channel Cav1.2 activity and long-term potentiation in rodents
Authors: Man Kwun Nok Mimi , Henderson Peter B. , Kim Karam , Shi Mei , Zhang Mingxu , Nieves-Cintron Madeline , Navedo Manuel F. , Horne Mary C. , Hell Johannes W. 
Published: July 2022

ABSTRACTThe cellular mechanisms mediating norepinephrine functions in brain to result in behaviors are unknown. We identified the L-type Ca2+ channel (LTCC) CaV1.2 as a principal target for Gq- coupled α1-adrenergic receptors (ARs). α1AR signaling increased LTCC activity in hippocampal neurons. This regulation required PKC-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with CaV1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of CaV1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by α1AR and formation of a signaling complex with PKC, Pyk2, and Src suggests that CaV1.2 is a central conduit for signaling by norepinephrine. Indeed, a form of hippocampal LTP in young mice requires both the LTCC and α1AR stimulation. Inhibition of Pyk2 and Src blocked this LTP, indicating that enhancement of CaV1.2 activity via α1AR - Pyk2 - Src signaling regulates synaptic strength.
MINI-EX: Integrative inference of single-cell gene regulatory networks in plants
Authors: Ferrari Camilla , Manosalva Pérez Nicolás , Vandepoele Klaas 
Published: July 2022

AbstractMulticellular organisms, such as plants, are characterized by highly specialized and tightly regulated cell populations, establishing specific morphological structures and executing distinct functions. Gene regulatory networks (GRNs) describe condition-specific interactions of transcription factor (TF) regulating the expression of target genes, underpinning these specific functions. As efficient and validated methods to identify cell-type specific GRNs from single-cell data in plants are lacking, limiting our understanding of the organization of specific cell-types in both model species and crops, we developed MINI-EX (Motif-Informed Network Inference based on single-cell Expression data), an integrative approach to infer cell-type specific networks in plants. MINI-EX uses single-cell transcriptomic data to define expression-based networks and integrates TF motif information to filter the inferred regulons, resulting in networks with increased accuracy. Next, regulons are assigned to different cell-types, leveraging cell-specific expression, and candidate regulators are prioritized using network centrality measures, functional annotations, and expression specificity. This embedded prioritization strategy offers a unique and efficient means to unravel signaling cascades in specific cell-types controlling a biological process of interest. We demonstrate MINI-EX’s stability towards input data sets with low number of cells and its robustness towards missing data, and we show it infers state-of-the-art networks with a better performance compared to related single-cell network tools. MINI-EX successfully identifies key regulators controlling root development in Arabidopsis and rice, Arabidopsis leaf development, and governing ear development in maize, enhancing our understanding of cell-type specific regulation and unraveling the role of different regulators controlling the development of specific cell-types in plants.
Context-dependent transcriptional remodeling of TADs during differentiation
Authors: Chahar Sanjay , Zouari Yousra Ben , Salari Hossein , Molitor Anne M , Kobi Dominique , Maroquenne Manon , Erb Cathie , Mossler Audrey , Karasu Nezih , Jost Daniel , Sexton Tom 
Published: July 2022

SummaryMetazoan chromosomes are organized into discrete domains (TADs), believed to contribute to the regulation of transcriptional programs. Despite extensive correlation between TAD organization and gene activity, a direct mechanistic link is unclear, with perturbation studies often showing little effect. To follow TAD dynamics during development, we used Capture Hi-C to interrogate the TADs around key differentially expressed genes during mouse thymocyte maturation, uncovering specific remodeling events. Notably, one TAD boundary was broadened to accommodate RNA polymerase elongation past the border, and sub-domains were formed around some activated genes without changes in CTCF binding. The ectopic induction of one gene was sufficient to recapitulate microdomain formation in embryonic stem cells, providing strong evidence that transcription can directly remodel chromatin structure. These results suggest that transcriptional processes drive complex, but non-universal, chromosome folding patterns that can be important in certain genomic contexts.
A novel Smg6 mouse model reveals regulation of circadian period and daily CRY2 accumulation through the nonsense-mediated mRNA decay pathway
Authors: Katsioudi Georgia , Dreos René , Arpa Enes S. , Gaspari Sevasti , Liechti Angelica , Sato Miho , Gabriel Christian H. , Kramer Achim , Brown Steven A. , Gatfield David 
Published: July 2022

AbstractNonsense-mediated mRNA decay (NMD) has been intensively studied as a surveillance pathway that degrades erroneous transcripts arising from mutations or RNA processing errors. While additional roles in controlling regular mRNA stability have emerged, possible functions in mammalian physiology in vivo have remained unclear. Here, we report a novel conditional mouse allele that allows converting the NMD effector nuclease SMG6 from wild-type to nuclease domain-mutant protein. We analyzed how NMD downregulation affects the function of the circadian clock, a system known to require rapid mRNA turnover. We uncover strong lengthening of free-running circadian periods for liver and fibroblast clocks, and direct NMD regulation of Cry2 mRNA, encoding a key transcriptional repressor within the rhythm-generating feedback loop. In the entrained livers of Smg6 mutant animals we reveal transcriptome-wide alterations in daily mRNA accumulation patterns, altogether expanding the known scope of NMD regulation in mammalian gene expression and physiology.
The human placenta exhibits a unique transcriptomic void
Authors: Gong Sungsam , Gaccioli Francesca , Aye Irving L.M.H. , Avellino Giulia , Cook Emma , Lawson Andrew R.J. , Harvey Luke M.R. , Smith Gordon C.S. , Charnock-Jones D. Stephen 
Published: July 2022

AbstractWe have recently demonstrated that the human placenta exhibits a unique genomic architecture with an unexpectedly high mutation burden(Coorens et al. 2021) and it is also well recognized that the placenta uniquely expresses many genes(Gong et al. 2021). However, the placenta is relatively understudied in systematic comparisons of gene expression in different organs. The aim of the present study was to identify transcripts which were uniquely absent or depleted, comparing the placenta with 46 other human organs. Here we show that 40/46 of the other organs had no transcripts which were selectively depleted and that of the remaining six, the liver had the largest number with 26. In contrast, the term placenta had 762 depleted transcripts. Gene Ontology analysis of this depleted set highlighted multiple pathways reflecting known unique elements of placental physiology. However, analysis of term samples demonstrated massive over representation of genes involved in mitochondrial function (P=5.8×10−10), including PGC-1α - the master regulator of mitochondrial biogenesis, and genes involved in polyamine metabolism (P=2.1×10−4). We conclude that the term placenta exhibits a unique metabolic environment.
Cytotoxic effect of Rotheca serrata on cancer cell lines MCF-7 and Neuroblastoma SH-SY5Y
Authors: Gadade Jayashree Pandurang , Patil Swaroopa Amit 
Published: July 2022

AbstractRotheca serrata (Lamiaceae), a highly medicinal plant is used as an antidote for snakebite and the plant possesses medicinal properties like hepatoprotective, antitussive, antioxidant, anticancer, neuro-protective, used in rheumatoid arthritis and is also a α-glucoside inhibitor. This work aimed to study the anticancerous effect of Rotheca serrata (root and leaf) on cancer cell lines MCF-7 (breast cancer cell line) and Neuroblastoma SH-SY5Y. The results indicated that the Methanolic extract of Rotheca serrata (root and leaf) showed high anticancer activity. Different concentrations of plant extracts (25, 50, 100, 200, 400 μg/ml) were used to study the anticancerous activity, amongst which the significant results were obtained for 400 μg/ml concentration (both root & leaf). Effective anticancer activity against MCF – 7 breast cancer cells was shown in methanoilc extracts and were expressed as IC 50 values; in root (IC 50 value= 61.8259 ± 7.428 μg/ml) and in leaf (IC 50 value = 78.1497 ± 6.316μg/ml). The MTT assay in case of neuroblastoma (SH-SY5Y) cell lines revealed that 400μg/ml concentration of leaf methanolic extract showed effective inhibition of cancer cells with IC 50 value 37.8462 ± 2.957 μg/ml as compared to IC 50 value of root methanolic extract which was 57.0895 ± 2.351 μg/ml.
Electric Field Responsive Nanotransducers for Glioblastoma
Authors: Jain Akhil , Jobson Isobel , Griffin Michaela , Rahman Ruman , Smith Stuart , Rawson Frankie 
Published: July 2022

AbstractElectric field therapies such as Tumor Treating Fields (TTFields) have emerged as a bioelectronic treatment for isocitrate dehydrogenase wild-type and IDH mutant grade 4 astrocytoma Glioblastoma (GBM). TTFields rely on alternating current (AC) electric fields (EF) leading to the disruption of dipole alignment and induced dielectrophoresis during cytokinesis. Although TTFields have a favourable side effect profile, particularly compared to cytotoxic chemotherapy, survival benefits remain limited (∼ 4.9 months) after an extensive treatment regime (20 hours/day for 18 months). The cost of the technology also limits its clinical adoption worldwide. Therefore, the discovery of new technology that can enhance survival benefit and improve the cost per added quality of life year per patient, of these TTFields will be of great benefit to cancer treatment and decrease healthcare costs worldwide. In this work, we report the role of electrically conductive gold (GNPs), dielectric silica oxide (SiO2), and semiconductor zinc oxide (ZnO) nanoparticles (NPs) as transducers for enhancing EF mediated anticancer effects on patient derived GBM cells. Physicochemical properties of these NPs were analyzed using spectroscopic, electron microscopy, and light-scattering techniques. In vitro TTFields studies indicated an enhanced reduction in the metabolic activity of patient-derived Glioma INvasive marginal (GIN 28) and Glioma contrast enhanced core (GCE 28) GBM cells in groups treated with NPs vs. control groups, irrespective of NPs dielectric properties. Our results indicate the inorganic NPs used in this work enhance the intracellular EF effects by virtue of bipolar dielectrophoretic and electrophoretic effects. This work presents preliminary evidence which could help to improve future EF applications for bioelectronic medicine. Furthermore, the merits of spherical morphology, excellent colloidal stability, and low toxicity, make these NPs ideal for future studies for elucidating the detailed mechanism and efficacy upon their delivery in GBM preclinical models.
Social and individual learners use different pathways to success in an ant mini-society
Authors: Glaser Simone M , Grüter Christoph 
Published: July 2022

AbstractAnimals can acquire information through individual learning or by copying others. Simulations suggest that social learning is expected to lead to better rewards, but experimental studies confirming this remain scarce. We tested how a well-known form of social learning in ants, tandem running, affects individual foraging success ofTemnothroax nylanderiforagers in controlled laboratory experiments. We manipulated the number and the variability of food sources and assessed the foraging choices of ants searching individually (i.e. scouts) or using social learning (i.e. recruits). We found that social learners indeed discovered better food sources than individual learners, but only in rich environments. However, social learners collected less food (∼60% fewer foraging trips) than scouts during our trials. Interestingly, individual learners improved their success over time by switching food sources more frequently than social learners. These experimental findings highlight that the relative value of social and individual learning in an ant society depend on the foraging environment and show different temporal dynamics. The ability of individual learners to exploit profitable food sources through a strategy of food source switching, while avoiding the opportunity costs of social learning can help explain why many social insects, especially those living in small colonies, do not use communication in foraging.
DBlink: Dynamic localization microscopy in super spatiotemporal resolution via deep learning
Authors: Saguy Alon , Alalouf Onit , Opatovski Nadav , Jang Soohyen , Heilemann Mike , Shechtman Yoav 
Published: July 2022

AbstractSingle molecule localization microscopy (SMLM) has revolutionized biological imaging, improving the spatial resolution of traditional microscopes by an order of magnitude. However, SMLM techniques depend on accumulation of many localizations over thousands of recorded frames to yield a single super-resolved image, which is time consuming. Hence, the capability of SMLM to observe dynamics has always been limited. Typically, a few minutes of data acquisition are needed to reconstruct a single super-resolved frame. In this work, we present DBlink, a novel deep-learning-based algorithm for super spatiotemporal resolution reconstruction from SMLM data. The input to DBlink is a recorded video of single molecule localization microscopy data and the output is a super spatiotemporal resolution video reconstruction. We use bi-directional long short term memory (LSTM) network architecture, designed for capturing long term dependencies between different input frames. We demonstrate DBlink performance on simulated data of random filaments and mitochondria-like structures, on experimental SMLM data in controlled motion conditions, and finally on live cell dynamic SMLM. Our neural network based spatiotemporal interpolation method constitutes a significant advance in super-resolution imaging of dynamic processes in live cells.
An isoform-specific function of Cdc42 in regulating mammalian Exo70 during axon formation
Authors: Ravindran Priyadarshini , Püschel Andreas W. 
Published: July 2022

SummaryThe highly conserved GTPase Cdc42 is an essential regulator of cell polarity and promotes exocytosis through the exocyst complex in budding yeast and Drosophila. In mammals, this function is performed by the closely related GTPase TC10 while mammalian Cdc42 does not interact with the exocyst. Axon formation is facilitated by the exocyst complex that tethers vesicles prior to their fusion to expand the plasma membrane. This function depends on the recruitment of the Exo70 subunit to the plasma membrane. Alternative splicing generates two Cdc42 isoforms that differ in their C-terminal 10 amino acids. Our results identify an isoform-specific function of Cdc42 in neurons. We show that the brain-specific Cdc42b isoform, in contrast to the ubiquitous isoform Cdc42u, can interact with Exo70. Cdc42b regulates exocytosis and axon formation downstream of its activator Arhgef7. Thus, the function of Cdc42 in regulating exocytosis is conserved in mammals but specific to one isoform.
Reproductive fitness is associated with female chronotype in a songbird
Authors: Womack Robyn J. , Capilla-Lasheras Pablo , McGlade Ciara L. O. , Dominoni Davide M. , Helm Barbara 
Published: July 2022

AbstractResearch on biological rhythms has revealed widespread variation in diel timing within populations. Repeatable individual chronotypes have been linked to performance in humans but, in free-living species, benefits of chronotype are poorly understood. To address this gap, we investigated fitness correlates of incubation patterns in female songbirds (great tit, Parus major) at urban and forest sites. We confirm repeatable chronotypes (r ≥ 0.31) and show novel links between chronotype and reproductive success. In both habitats, females that started activity earlier in the day raised more fledglings. We also observed that forest females started their day at a similar time throughout the breeding season, whereas urban females tied their onset of activity closely to sunrise. Our study points to possible mechanisms that underlie chronotype variation and provides sought-after evidence for its relevance to fitness.
MRN and Topoisomerase IIIα-RMI1/2 synchronize DNA resection motor proteins
Authors: Soniat Michael M. , Nguyen Giaochau , Kuo Hung-Che , Finkelstein Ilya J. 
Published: July 2022

AbstractDNA resection—the nucleolytic processing of broken DNA ends—is the first step of homologous recombination. Resection is catalyzed by the resectosome, a multi-enzyme complex that includes BLM helicase, DNA2 or EXO1 nucleases, and additional DNA-binding proteins. Although the molecular players have been known for over a decade, how the individual proteins work together to regulate DNA resection remain unknown. Using single-molecule imaging, we characterized the roles of MRN and TOP3A-RMI1/2 during long-range DNA resection. BLM partners with TOP3A-RMI1/2 to form the BTRR complex (or BLM dissolvasome). TOP3A-RMI1/2 aids BLM in initiating DNA unwinding, and along with MRN, stimulates DNA2-mediated resection. Furthermore, MRN promotes the association between BTRR and DNA, and synchronizes BLM and DNA2 translocation to prevent BLM from pausing during resection. Together, this work provides direct observation of how MRN and DNA2 harness the BTRR complex to resect DNA efficiently and how TOP3A-RMI1/2 regulates BLM’s helicase activity to promote efficient DNA repair.