bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of sexual dimorphism on pollinator behaviour in a dioecious species
Authors: Moquet L. , Jacquemart A-L , Dufay M. , De Cauwer I. 
Published: April 2021

SummaryFloral traits often display sexual dimorphism in insect-pollinated dioecious plant species, with male individuals typically being showier than females. While this strategy is theorized to be optimal when pollinators are abundant, it might represent a risk when they become scarce, because the disproportionately high number of visits on the most attractive sex, males, might preclude efficient pollen transfer from males to females. Here, the effect of sexual dimorphism on pollination efficiency was assessed in experimental arrays of dioeciousSilene dioicathat were exposed to one frequent visitor of the species,Bombus terrestris, and that differed in the magnitude of sexual dimorphism for either flower number or flower size. While flower size dimorphism did not impact pollination efficiency, we found that flower number dimorphism negatively affected the number of visits on female plants, on female flowers and on the number of female flowers visited after a male flower. However, flower number dimorphism had no effect on the number of pollen grains deposited per stigma, presumably because the decrease in the number of visits to female flowers was compensated by a higher number of pollen grains deposited per visit.
Quantification and uncertainty of root growth stimulation by elevated CO2in mature temperate deciduous forest
Authors: Ziegler Clare , Kulawska Aleksandra , Kourmouli Angeliki , Hamilton Liz , Shi Zongbo , MacKenzie A. Rob , Dyson Rosemary J. , Johnston Iain G. 
Published: April 2021

AbstractIncreasing CO2levels are a major global challenge, and the extent to which increasing anthropogenic CO2emissions can be mitigated by natural carbon sinks remains poorly understood. The uptake of elevated CO2(eCO2) by the terrestrial biosphere, and subsequent sequestration as biomass in ecosystems, may act as a negative feedback in the carbon budget, but remains hard to quantify in natural ecosystems. Here, we combine large-scale field observations of fine root stocks and flows, derived from belowground imaging and soil cores, with image analysis, stochastic modelling, and statistical inference, to elucidate belowground root dynamics in a mature temperate deciduous forest under free-air CO2enrichment to 150ppm above ambient levels. Using over 67kframes of belowground observation, we observe that eCO2leads to relatively faster root production (a peak volume fold change of 4.52 ± 0.44 eCO2versus 2.58 ± 0.21 control). We identify an increase in existing root elongation relative to root mass decay as the likely causal mechanism for this acceleration. Direct physical analysis of biomass and width measurements from 552 root systems recovered from soil cores support this picture, with lengths and widths of fine roots significantly increasing under eCO2. We use dynamic measurements to estimate fine root contributions to net primary productivity, finding an increase under eCO2, with an estimated mean annual 204 ± 93 g dw m−2yr−1eCO2versus 140 ± 60 g dw m−2yr−1control. We also quantify and discuss the uncertainties in such productivity measurements. This multi-faceted approach thus sheds quantitative light on the challenging characterisation of the eCO2response of root biomass in mature temperate forests.
Design and application of a knowledge network for automatic prioritization of drug mechanisms
Authors: Mayers Michael , Tu Roger , Steinecke Dylan , Li Tong Shu , Queralt-Rosinach Núria , Su Andrew I. 
Published: April 2021

AbstractMotivationDrug repositioning is an attractive alternative to de novo drug discovery due to reduced time and costs to bring drugs to market. Computational repositioning methods, particularly non-black-box methods that can account for and predict a drug’s mechanism, may provide great benefit for directing future development. By tuning both data and algorithm to utilize relationships important to drug mechanisms, a computational repositioning algorithm can be trained to both predict and explain mechanistically novel indications.ResultsIn this work, we examined the 123 curated drug mechanism paths found in the drug mechanism database (DrugMechDB) and after identifying the most important relationships, we integrated 18 data sources to produce a heterogeneous knowledge graph, MechRepoNet, capable of capturing the information in these paths. We applied the Rephetio repurposing algorithm to MechRepoNet using only a subset of relationships known to be mechanistic in nature and found adequate predictive ability on an evaluation set with AUROC value of 0.83. The resulting repurposing model allowed us to prioritize paths in our knowledge graph to produce a predicted treatment mechanism. We found that DrugMechDB paths, when present in the network were rated highly among predicted mechanisms. We then demonstrated MechRepoNet’s ability to use mechanistic insight to identify a drug’s mechanistic target, with a mean reciprocal rank of .525 on a test set of known drug-target interactions. Finally, we walked through a repurposing example of the anti-cancer drug imantinib for use in the treatment of asthma, to demonstrate this method’s utility in providing mechanistic insight into repurposing predictions it provides.Availability and implementationThe Python code to reproduce the entirety of this analysis is available at:https://github.com/SuLab/MechRepoNetContactasu@scripps.eduSupplementary informationSupplemental information is available at Bioinformatics online.
Increased pattern similarity in two major olfactory cortices despite higher sparseness levels
Authors: Markind Chaviva , Kundu Prosenjit , Barak Mor , Haddad Rafi 
Published: April 2021

AbstractPattern separation is a fundamental process that enhances discrimination of similar stimuli and can be achieved by sparsening the neural activity and expanding the coding space. Odor stimuli evoke patterns of activity in the olfactory bulb (OB) and these activity patterns are projected to several cortical regions that contain larger numbers of neurons and show sparser activity levels. However, whether these projected patterns are better separated is still unclear. Here we compared odor responses in the OB, anterior piriform cortex (aPC) and anterior olfactory nucleus (AON) to the exact same odor stimuli. We found that odor representations are more similar, noisier and less distinctive in aPC and AON than in the OB. The increase in similarity was observed for both similar and dissimilar odors. Modeling odor transformation from the OB to the olfactory cortex using simulated as well as actual OB odor responses as inputs, demonstrates that the observed rise in odor representation similarity can be explained by assuming biologically plausible variation in the number of OB inputs each cortical neuron receives. We discuss the possible advantages of our findings to odor processing in the aPC and AON.HighlightsOdor representations in the aPC and AON are more correlated despite increase in sparseness levels.Odor identity is best represented in the OB.Variance in the number of inputs from OB can explain the reduction in odor separation.
Early low-level developmental arsenic exposure impacts mouse hippocampal synaptic function
Authors: Foley Karl F.W. , Barnett Daniel , Cory-Slechta Deborah A. , Xia Houhui 
Published: April 2021

AbstractBackgroundArsenic is a well-established carcinogen known to increase all-cause mortality, but its effects on the central nervous system are less well understood. Recent epidemiological studies suggest that early life exposure to arsenic is associated with learning deficits and behavioral changes, and increased arsenic exposure continues to affect an estimated 200 million individuals worldwide. Previous studies on arsenic exposure and synaptic function have demonstrated a decrease in synaptic transmission and long-term potentiation in adult rodents, but have relied on in vitro or extended exposure in adulthood. Therefore, little is known about the effect of arsenic exposure in development.ObjectiveHere, we studied the effects of gestational and early developmental arsenic exposure in juvenile mice. Specifically, our objective was to investigate the impact of arsenic exposure on synaptic transmission and plasticity in the hippocampus.MethodsC57BL/6 females were exposed to arsenic (0, 50ppb, 36ppm) in their drinking water two weeks prior to mating and continued to be exposed to arsenic throughout gestation and after parturition. We then performed field recordings in acute hippocampal slices from the juvenile offspring prior to weaning (P17-P23). In this paradigm, the juvenile mice are only exposed to arsenic in utero and via the mother’s milk.ResultsHigh (36ppm) and relatively low (50ppb) arsenic exposure both lead to decreased basal synaptic transmission in the hippocampus of juvenile mice. There was a mild decrease in paired-pulse facilitation in juvenile mice exposed to high, but not low, arsenic, suggesting the alterations in synaptic transmission are primarily post-synaptic. Finally, high developmental arsenic exposure led to a significant increase in long-term potentiation.DiscussionThese results suggest that indirect, ecologically-relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies.
Geobacter sulfurreducensinner membrane cytochrome CbcBA controls electron transfer and growth yield near the energetic limit of respiration
Authors: Joshi Komal , Chan Chi Ho , Bond Daniel R. 
Published: April 2021

AbstractGeobacter sulfurreducensutilizes extracellular electron acceptors such as Mn(IV), Fe(III), syntrophic partners, and electrodes that vary from +0.4 to −0.3 Vvs.Standard Hydrogen Electrode (SHE), representing a potential energy span that should require a highly branched electron transfer chain. Here we describe CbcBA, abc-type cytochrome essential near the thermodynamic limit of respiration when acetate is the electron donor. Mutants lackingcbcBAceased Fe(III) reduction at −0.21 Vvs.SHE, could not transfer electrons to electrodes between −0.21 and −0.28 V, and could not reduce the final 10% – 35% of Fe(III) minerals. As redox potential decreased during Fe(III) reduction,cbcBAwas induced with the aid of the regulator BccR to become one of the most highly expressed genes inG. sulfurreducens. Growth yield (CFU/mM Fe(II)) was 112% of WT in ΔcbcBA, and deletion ofcbcL(a differentbc-cytochrome essential near −0.15 V) in ΔcbcBAincreased yield to 220%. Together with ImcH, which is required at high redox potentials, CbcBA represents a third cytoplasmic membrane oxidoreductase inG. sulfurreducens. This expanding list shows how these important metal-reducing bacteria may constantly sense redox potential to adjust growth efficiency in changing environments.
Collateral Responses to Classical Cytotoxic Chemotherapies are Heterogeneous and Sensitivities are Sparse
Authors: Dalin Simona , Lauffenburger Douglas A. , Hemann Michael T. 
Published: April 2021

AbstractChemotherapy resistance is a major obstacle to curing cancer patients. Combination drug regimens have shown promise as a method to overcome resistance; however, to date only some cancers have been cured with this method. Collateral sensitivity – the phenomenon whereby resistance to one drug is co-occurrent with sensitivity to a second drug – has been gaining traction as a promising new concept to guide rational design of combination regimens. Here we survey collateral responses to acquisition of resistance to four classical chemotherapy agents. Although collateral sensitivities have been documented for antibiotics and targeted cancer therapies, we did not observe collateral sensitivities to any of the cytotoxic agents we studied. Interestingly, we did observe heterogeneity in the phenotypic response to acquisition of resistance to each drug, suggesting the existence of multiple different states of resistance for each drug. Surprisingly, this phenotypic heterogeneity was unrelated to transcriptomic heterogeneity in the resistant cell lines. These features of phenotypic and transcriptomic heterogeneity must be taken into account in future studies of treated tumor subclones and in design of chemotherapy combinations.
Extensive transgressive gene expression in testis but not ovary in the homoploid hybrid Italian sparrow
Authors: Yazdi Homa Papoli , Ravinet Mark , Rowe Melissah , Sætre Glenn-Peter , Øien Guldvog Caroline , Eroukhmanoff Fabrice , Marzal Alfonso , Magallanes Sergio , Runemark Anna 
Published: April 2021

AbstractHybridization can result in novel allelic combinations which can impact the hybrid phenotype through changes in gene expression. While mis-expression in F1 hybrids is well documented, how gene expression evolves in stabilized hybrid taxa remains an open question. As gene expression evolves in a stabilizing manner, break-up of co-evolvedcis- andtrans-regulatory elements could lead to transgressive patterns of gene expression in hybrids. Here, we address to what extent gonad gene expression has evolved in an established and stable homoploid hybrid, the Italian sparrow (Passer italiae). Through comparison of gene expression in gonads from individuals of the two parental species (i.e., house and Spanish sparrow) to that of Italian sparrows, we find evidence for strongly transgressive expression in male Italian sparrows - 22% of testis genes exhibit expression patterns outside the range of both parent species. In contrast, Italian sparrow ovary expression was similar to that of one of the parent species, the house sparrow (Passer domesticus). Moreover, the Italian sparrow testis transcriptome is 26 times as diverged from those of the parent species as the parental transcriptomes are from each other, despite being genetically intermediate. This highlights the potential for regulation of gene expression to produce novel variation following hybridization. Genes involved in mitochondrial respiratory chain complexes and protein synthesis are enriched in the subset that is over-dominantly expressed in Italian sparrow testis, suggesting that selection on key functions have molded the hybrid Italian sparrow transcriptome.
A direct lateral entorhinal cortex to hippocampal CA2 circuit conveys social information required for social memory
Authors: Lopez-Rojas Jeffrey , de Solis Christopher A. , Leroy Felix , Kandel Eric R. , Siegelbaum Steven A. 
Published: April 2021

AbstractThe storage of information by the hippocampus in long-term memory is thought to involve two distinct but related processes. First, the hippocampus determines whether a given stimulus is novel or familiar; next, the hippocampus stores the novel information in long-term memory. To date, the neural circuits that detect novelty and their relation to the circuits that store information of a specific memory are poorly understood. Here we address this question by examining the circuits by which the CA2 region of the hippocampus, which is essential for social memory, both detects social novelty and stores social memory. CA2, like the more thoroughly studied CA1 region, receives its major excitatory input from the entorhinal cortex through both a direct monosynaptic and indirect trisynaptic pathway. We find that the direct inputs to CA2 from the lateral entorhinal cortex, but not the indirect trisynaptic inputs, provide social information that is required for social memory. However, these direct inputs fail to discriminate a novel from a familiar animal. Thus, social novelty and social identity signals are likely conveyed through separate pathways, with the entorhinal cortex providing specific multisensory information about an animal’s identity and novelty detection requiring a local computation within CA2.
Dynamics of absolute and relative disparity processing in human visual cortex
Authors: Kaestner Milena , Evans Marissa L. , Chen Yulan D. , Norcia Anthony M. 
Published: April 2021

ABSTRACTCortical processing of binocular disparity is believed to begin in V1 where cells are sensitive to absolute disparity, followed by the extraction of relative disparity in higher visual areas. While much is known about the cortical distribution and spatial tuning of disparity-selective neurons, the relationship between their spatial and temporal properties is less well understood. Here, we use steady-state Visual Evoked Potentials and dynamic random dot stereograms to characterize the temporal dynamics of spatial mechanisms in human visual cortex that are primarily sensitive to either absolute or relative disparity. Stereograms alternated between disparate and non-disparate states at 2 Hz. By varying the spatial frequency content of the disparate fields from a planar surface to corrugated ones, we biased responses towards absolute vs. relative disparities. Reliable Components Analysis was used to derive two dominant sources from the 128 channel EEG records. The first component (RC1) was maximal over the occipital pole while the second component (RC2) was maximal over right lateral occipital electrodes. In RC1, first harmonic responses were sustained, tuned for corrugation frequency, and sensitive to the presence of disparity references, consistent with prior psychophysical sensitivity measurements. By contrast, the second harmonic, associated with transient processing, was not spatially tuned and was indifferent to references, consistent with it being generated by an absolute disparity mechanism. In RC2, the sustained response component showed similar tuning and sensitivity to references. However, sensitivity for absolute disparity dropped off, and transient signals were mainly driven by the lowest corrugation frequencies.SIGNIFICANCE STATEMENTSustained and transient mechanisms have been demonstrated across sensory systems and may reflect a common coding strategy. This strategy may be useful for the analysis of the form and duration of complex events in the case of sustained signals, and the onset and location of events in the case of transient signals. Here, we provide direct neural correlates of sustained and transient disparity mechanisms in human visual cortex. Early visual cortex is sensitive to both relative and absolute disparity, with the former being processed in a sustained fashion and the latter in a more transient fashion. Outside of early visual cortex, sustained relative disparity responses are readily measurable, but transient responses and responses to absolute disparity are not.
Arabidopsis CALMODULIN-BINDING PROTEIN 60b plays dual roles in plant immunity
Authors: Huang Weijie , Wu Zhongshou , Tian Hainan , Li Xin , Zhang Yuelin 
Published: April 2021

AbstractArabidopsis SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1) and CALMODULIN-BINDING PROTEIN 60g (CBP60g) are two master transcription factors that regulate many defense-related genes in plant immunity. They are required for immunity downstream of the receptor-like protein SUPPRESSOR OF NPR1-1, CONSTITUTIVE 2 (SNC2). Constitutive defense responses in the gain-of-function autoimmunesnc2-1Dmutant are modestly affected by eithersard1orcbp60gsingle mutants, but completely suppressed by thesard1 cbp60gdouble mutant. Here we report that CBP60b, another member of the CBP60 family, also functions as a positive regulator of SNC2-mediated immunity. Loss-of-function mutations ofCBP60bsuppress the constitutive expression ofSARD1and enhanced disease resistance incbp60g-1 snc2-1D, whereas over-expression ofCBP60bleads to elevatedSARD1expression and constitutive defense responses. In addition, transient expression ofCBP60binNicotiana benthamianaactivates the expression of thepSARD1::luciferasereporter gene. Chromatin immunoprecipitation assay further showed that CBP60b is recruited to the promoter region ofSARD1, suggesting that it directly regulatesSARD1expression. Interestingly, knocking outCBP60bin the wild type background leads to ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1)-dependent autoimmunity, suggesting that CBP60b is required for the expression of a guardee/decoy or a negative regulator in immunity mediated by receptors carrying an N-terminal TIR (Toll-interleukin-1 receptor-like) domain.Significance statementArabidopsis SARD1 serves as a master transcription factor in plant immunity. In this study, we showed that CBP60b positively regulatesSARD1expression, and TIR signaling is activated when CBP60b is inactivated.
Dopaminergic but not Cholinergic Neurodegeneration is Correlated with Gait Disturbances in PINK1 Knockout Rats
Authors: DeAngelo VM , Hilliard JD , McConnell GC 
Published: April 2021

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by gait dysfunction in later stages of the disease. PD hallmarks include a decrease in stride length, run speed, and swing time; an increase in stride time, stance time, and base of support; dopaminergic degeneration in the basal ganglia; and cholinergic degeneration in the pedunculopontine nucleus (PPN). A progressive animal model of PD is needed to identify treatments for gait dysfunction. The goal of this study was to quantify progressive gait degeneration in PTEN-induced putative kinase 1 knockout (P1KO) rats and investigate neurodegeneration as potential underlying mechanisms. Gait analysis was performed in male P1KO and wild-type rats at 5 and 8 months of age and immunohistochemical analysis at 8 months. Multiple parameters of volitional gait were measured using a runway system. P1KO rats exhibited significant gait deficits at 5 months, but not 8 months. Gait abnormalities improved over time suggesting compensation during behavioral testing. At 8 months a 15% loss of tyrosine hydroxylase (TH) in the striatum, a 27% loss of TH-positive cells in the substantia nigra pars compacta, and no significant loss of choline acetyltransferase-positive cells in the PPN was found. Dopaminergic cell loss may contribute to gait deficits in the P1KO model, but not cholinergic cell loss. The P1KO rat with the greatest dopamine loss exhibited the most pronounced PD-like gait deficits, highlighting variability within the model. Further analysis is required to determine the suitability of the P1KO rat as a progressive model of gait abnormalities in PD.