bluuebunny/crossref_metadata_2025_split huggingface dataset:
The CBP KIX domain regulates long-term memory and circadian activity
Authors: Chatterjee Snehajyoti , Angelakos Christopher C. , Bahl Ethan , Hawk Joshua D. , Gaine Marie E. , Poplawski Shane G. , Schneider-Anthony Anne , Yadav Manish , Porcari Giulia S. , Cassel Jean-Christophe , Giese K. Peter , Michaelson Jacob J. , Lyons Lisa C. , Boutillier Anne-Laurence , Abel Ted 
Published: June 2020

AbstractCREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors. Identifying specific domain functions for multi-action proteins is essential to understand processes necessary for healthy living including cognitive function and a robust circadian clock. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIXmice with mutations that prevent phospho-CREB (Ser133) binding. We found that CBPKIX/KIXmice were impaired in long-term, but not short-term spatial memory in the Morris water maze. Using an unbiased analysis of gene expression after training for hippocampus-dependent memory, we discovered dysregulation of CREB and CLOCK target genes and downregulation of circadian genes in CBPKIX/KIXmice. With our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity in CBPKIX/KIXmice. CBPKIX/KIXmice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark, although phase resetting to light was comparable to wildtype. These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domainin vivoon circadian rhythms.
Cancer cells depend on environmental lipids for proliferation when electron acceptors are limited
Authors: Li Zhaoqi , Ji Brian W. , Dixit Purushottam D. , Lien Evan C. , Tchourine Konstantine , Hosios Aaron M. , Abbott Keene L. , Westermark Anna M. , Gorodetsky Elizabeth F. , Sullivan Lucas B. , Vander Heiden Matthew G. , Vitkup Dennis 
Published: June 2020

AbstractIt is not well understood how physiological environmental conditions and nutrient availability influence cancer cell proliferation. Production of oxidized biomass, which requires regeneration of the cofactor NAD+, can limit cancer cell proliferation1-5. However, it is currently unclear which specific metabolic processes are constrained by electron acceptor availability, and how they affect cell proliferation. Here, we use computational and experimental approaches to demonstrate thatde novolipid biosynthesis can impose an increased demand for NAD+ in proliferating cancer cells. While some cancer cells and tumors synthesize a substantial fraction of their lipidsde novo6, we find that environmental lipids are crucial for proliferation in hypoxia or when the mitochondrial electron transport chain is inhibited. Surprisingly, we also find that even the reductive glutamine carboxylation pathway to produce fatty acids is impaired when cancer cells are limited for NAD+. Furthermore, gene expression analysis of 34 heterogeneous tumor types shows that lipid biosynthesis is strongly and consistently negatively correlated with hypoxia, whereas expression of genes involved in lipid uptake is positively correlated with hypoxia. These results demonstrate that electron acceptor availability and access to environmental lipids can play an important role in determining whether cancer cells engage inde novolipogenesis to support proliferation.
Isoform-specific aPKC renders primary cilia dispensable for Hedgehog signaling and basal cell carcinoma growth
Authors: Nguyen Tuyen T. L. , Wong Kirsten N. , Jeon Ung Seop , Jhumkhawala Vama , Luy Daniel , Tan Kevin C. , Wickramatunga Ishini , Kumar Vinay , England Whitney E. , Doan Linda T. , Spitale Robert C. , Atwood Scott X. 
Published: June 2020

AbstractPrimary cilia loss is a common feature of advanced cancers. While primary cilia are necessary to initiate Hedgehog (HH)-driven cancers, how HH pathway activity is maintained in advanced cancers devoid of primary cilia is unclear. Here, we find that HH-driven basal cell carcinoma (BCC) accumulates mutations in Alström and Usher syndrome genes. Loss of Alström and Usher syndrome gene expression, which are common underlying causes of deafness and blindness, suppresses primary ciliogenesis and HH signaling but enhances expression of atypical protein kinase C iota/lambda (aPKC), a GLI1 kinase necessary for advanced BCC growth. We show that aPKC expression is inversely correlated with primary ciliogenesis and that superficial BCCs display less primary cilia and higher aPKC expression, with the opposite trend in nodular BCC subtypes. Surprisingly, a constitutively active isoform of aPKC but not full-length protein drives HH pathway activity. Overexpression of the constitutively active aPKC variant can maintain HH pathway activity and tumor growth in the absence of primary cilia. Our results suggest tumors enhance isoform-specific expression of aPKC to prevent mutation-induced cessation of tumor growth.
A new method for distinguishing human and mouse cellsin situ
Authors: Wang Yongqiang , Huang Zixian , Hu Kaishun , Peng Jiangyun , Yao Weicheng , Deng Weixi , Zuo Jiyuan , Zhang Yin , Yin Dong 
Published: June 2020

AbstractThe mouse xenograft model is one of the most widely used animal model for biomedicine research. It is vital to distinguish the cells from different species, especially for the spatial distribution information. However, the available strategies of species-specific detection are either inapplicablein situor of low specificity. Here, we reported a method based on DAPI staining, which offers an effective, convenient way that accurately identifies human and mouse nuclei at single-cell levelin situ. This method was proven to be effective in cell co-culture and tumor xenograft tissue section. Microscopic imaging results shows obvious DAPI plaques-like structures in mouse nuclei, but absent in human nuclei. Moreover, we found these structures are co-localized with mouse major satellite DNA, which is located pericentromere in mouse, but absent in human. Our study provides a high-performance method that can be widely used for distinguish human and mouse cellin situ.
Engineering of Phytosterol-Producing Yeast Platforms for Functional Reconstitution of Downstream Biosynthetic Pathways
Authors: Xu Shanhui , Chen Curtis , Li Yanran 
Published: June 2020

AbstractAs essential structural molecules for plant plasma membranes, phytosterols are key intermediates for the synthesis of many downstream specialized metabolites of pharmaceutical or agricultural significance, such as brassinosteroids and withanolides.Saccharomyces cerevisiaehas been widely used as an alternative producer for plant secondary metabolites. Establishment of heterologous sterol pathways in yeast, however, has been challenging due to either low efficiency or structural diversity, likely a result of crosstalk between the heterologous phytosterol and the endogenous ergosterol biosynthesis. For example, in this study, we engineered campesterol production in yeast using plant enzymes; although we were able to enhance the titer of campesterol to ~40mg/L by upregulating the mevalonate pathway, no conversion to downstream products was detected upon the introduction of downstream plant enzymes. Further investigations uncovered two interesting observations about sterol engineering in yeast. First, many heterologous sterols tend to be efficiently and intensively esterified in yeast, which drastically impedes the function of downstream enzymes. Second, yeast can overcome the growth deficiency caused by altered sterol metabolism through repeated culture. By employing metabolic engineering, strain evolution, fermentation engineering, and pathway reconstitution, we were able to establish a set of phytosterol-producing yeast strains with decent growth and titer of campesterol (~ 7mg/L), β-sitosterol (~2mg/L), 22-hydroxycampesterol (~1mg/L), and 22-hydroxycampest-4-en-3-one (~4mg/L). This work resolves the technical bottlenecks in phytosterol-derived pathway reconstitution in the backer’s yeast and opens up opportunities for efficient bioproduction and pathway elucidation of this group of phytochemicals.
Neural systems underlying the learning of cognitive effort costs
Authors: Sayali Ceyda , Badre David 
Published: June 2020

AbstractPeople balance the benefits of cognitive work against the costs of cognitive effort. Models that incorporate prospective estimates of the costs of cognitive effort into decision making require a mechanism by which these costs are learned. However, it remains open what brain systems are important for this learning, particularly when learning is not tied explicitly to a decision about what task to perform. In this fMRI experiment, we parametrically manipulated the level of effort a task requires by increasing task switching frequency across six task contexts. In a scanned learning phase, participants implicitly learned about the task switching frequency in each context. In a subsequent test phase, participants made selections between pairs of these task contexts. We modeled learning within a reinforcement learning framework, and found that effort expectations that derived from task-switching probability and response time (RT) during learning were the best predictors of later choice behavior. Prediction errors (PE) from these two models were associated with FPN during distinct learning epochs. Specifically, PE derived from expected RT was most correlated with the fronto-parietal network early in learning, whereas PE derived from expected task switching frequency was correlated with the fronto-parietal network late in learning. These results suggest that multiple task-related factors are tracked by the brain while performing a task that can drive subsequent estimates of effort costs.
Evolutionary and demographic consequences of temperature-induced masculinization under climate warming: the effects of mate choice
Authors: Nemesházi Edina , Kövér Szilvia , Bókony Veronika 
Published: June 2020

AbstractBackgroundOne of the dangers of global climate change to wildlife is distorting sex ratios by temperature-induced sex reversals in populations where sex determination is not exclusively genetic, potentially leading to population collapse and/or sex-determination system transformation. Here we introduce a new concept on how these outcomes may be altered by mate choice if sex-chromosome-linked phenotypic traits allow females to choose between normal and sex-reversed (genetically female) males.ResultsWe developed a theoretical model to investigate if preference for sex-reversed males would spread and affect demographic and evolutionary processes under climate warming. We found that preference for sex-reversed males 1) more likely spread in ZW/ZZ than in XX/XY sex-determination systems, 2) in populations starting with ZW/ZZ system, it significantly hastened the transitions between different sex-determination systems and maintained more balanced adult sex ratio for longer compared to populations where all females preferred normal males; and 3) in ZZ/ZW systems with low but nonzero viability of WW individuals, a widespread preference for sex-reversed males saved the populations from early extinction.ConclusionsOur results suggest that climate change may affect the evolution of mate choice, which in turn may influence the evolution of sex-determination systems, sex ratios, and thereby adaptive potential and population persistence.
Suppression of pyramidal neuron G protein-gated inwardly rectifying K+ channel signaling impairs prelimbic cortical function and underlies stress-induced deficits in cognitive flexibility
Authors: Anderson Eden M , Loke Steven , Wrucke Benjamin , Engelhardt Annabel , Hess Evan , Wickman Kevin , Hearing Matthew C 
Published: June 2020

AbstractBackgroundImbalance in prefrontal cortical (PFC) pyramidal neuron excitation:inhibition is thought to underlie symptomologies shared across stress-related disorders and neuropsychiatric disease, including dysregulation of emotion and cognitive function. G protein-gated inwardly rectifying K+(GIRK/Kir3) channels mediate excitability of medial PFC pyramidal neurons, however the functional role of these channels in mPFC-dependent regulation of affect, cognition, and cortical dynamics is unknown.MethodsIn mice harboring a ‘floxed’ version of the kcnj3 (Girk1) gene, we used a viral-cre approach to disrupt GIRK1-containing channel expression in pyramidal neurons within the prelimbic (PL) or infralimbic (IL) cortices. Additional studies used a novel model of chronic unpredictable stress (CUS) to determine the impact on PL GIRK-dependent signaling and cognitive function.ResultsIn males, loss of pyramidal GIRK-dependent signaling in the PL, but not IL, differentially impacted measures of affect and motivation, and impaired working memory and cognitive flexibility. CUS produced similar deficits in affect and cognition that paralleled a reduction in PL pyramidal GIRK-dependent signaling akin to viral approaches. Viral- and stress-induced behavioral deficits were rescued by systemic injection of a novel, GIRK1-selective agonist, ML-297. Unexpectedly, neither ablation of PL GIRK-dependent signaling or exposure to the CUS regimen impacted affect or cognition in female mice.ConclusionsGIRK-dependent signaling in male mice, but not females, is critical for maintaining optimal PL function and behavioral control. Disruption of this inhibition may underlie stress-related dysfunction of the PL and represent a therapeutic target for treating stress-induced deficits in affect regulation and impaired cognition that reduce quality of life.
Indole acetic acid and lipopeptide-producing endophytic bacteria fromTaxus chinesis: toxicity evaluation of metabolic products
Authors: Dong Mengmeng , Yuan Bo , Wang Jingyi , Fu Lizhong , Kai Guoyin , Jiang Jihong 
Published: June 2020

AbstractEndophytes play an important role in plant growth and development. Some one can produce auxins, ACCs, iron carriers, and so on to help plants grow and resist unhealthy growth environments. In addition, they can produce certain antimicrobial substances to resist pests and diseases. Among them,Bacillusis the most common beneficial endophytic bacterium in plants. In this paper, 20 IAA-producing strains were screened from endophytic bacteria isolated fromTaxus chinensis var. maireiplant tissues by high-performance liquid-chromatography (HPLC). Based on the 20 IAA-producing strains, LC-TOF-MS technology was used to screen lipopeptide-producingBacillussp. As a result, three strains (KLBMPTC01, KLBMPTC10, and KLBMPTC29) ofBacillus-producing lipopeptides with abundant contents and species were obtained. According to the situation of the IAA and lipopeptides produced by these strains, KLBMPTC10 was selected as the experimental strain for later toxicological tests. In an Ames test and oral toxicity experiments in mice, we did not detect mutagenicity and other physiological toxicity. This is hoping to provide a theoretical basis for forest resource protection and biofertiliser production therewith.
The genetic signatures ofSalmonellaTyphi carriage in the human gallbladder
Authors: Duy Pham Thanh , Vu Thieu Nga Tran , Nguyen To Nguyen Thi , Dan Thanh Ho Ngoc , Dongol Sabina , Karkey Abhilasha , Carey Megan , Basnyat Buddha , Dougan Gordon , Rabaa Maia A , Baker Stephen 
Published: June 2020

AbstractDespite recent gains in typhoid fever control, asymptomatic carriage ofSalmonellaTyphi in the gallbladder remains an enigma. Aiming to understand ifS.Typhi in the gallbladder are vital for transmission and/or adapted for long-term colonisation we performed whole genome sequencing on a collection ofS. Typhi isolated from the gallbladders of typhoid carriers. These sequences were compared to contemporaneous sequences from organisms isolated from the blood of acute patients.S. Typhi carriage was not restricted to any particular genotype or conformation of antimicrobial resistance genes but reflective of the general population. However, gallbladder isolates had a higher genetic variability than acute isolates, with median pairwise SNP distances of 21 and 13 SNPs (p=2.8×10−9), respectively. This variation was associated with a higher prevalence of nonsense mutations in the gallbladder isolates in the predominant genotype. Notably, gallbladder isolates displayed a higher frequency of non-synonymous mutations in genes encoding hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. Particularly, we identified several gallbladder-specific non-synonymous mutations involved in LPS synthesis and modification, with some isolates lacking the Vi capsular polysaccharide vaccine target due to a 134Kb deletion. Long-term gallbladder carriage ofS. Typhi results in atypically long branch lengths that can distinguish between carriage and acute infection. Our data strongly suggests typhoid carriers are unlikely to play a principal role in disease transmission in endemic settings, but that the hostile environment of the human gallbladder may generate new antigenic variants through immune selection.
Recurrent Dynamics of Rupture Transitions of Single Giant Vesicles at Solid Surfaces
Authors: Ngassam V.N. , Su W.-C. , Gettel D. L. , Deng Y. , Yang Z. , Wang-Tomic N. , Sharma V. P. , Purushothaman S. , Parikh A. N. 
Published: June 2020

ABSTRACTSingle giant vesicles (GVs) rupture spontaneously from their salt-laden suspension onto solid surfaces. At hydrophilic surfaces, they rupture via a recurrent burst-heal dynamics: during burst, single pores nucleate at the contact boundary of the adhering vesicles facilitating asymmetric spreading and producing a “heart” shaped membrane patch. During the healing phase, the competing pore closure produces a daughter vesicle. At hydrophobic surfaces, by contrast, the GVs rupture via a distinctly different, yet recurrent, bouncing ball rhythm: Rendered tense by the substrate interactions, GVs porate and spread monomolecular layer on the hydrophobic surface in a symmetric manner. Here too, the competition from pore closure produces a daughter vesicle, which re-engages with the substrate. In both cases, the pattern of burst-reseal events repeats multiple times splashing and spreading the vesicular fragments as bilayer patches at the solid surface in a pulsatory manner. These remarkable recurrent dynamics arise not because of the elastic properties of the solid surface but because the competition between membrane spreading and pore healing, prompted by the surface-energy dependent adhesion, determine the course of the topological transition.STATEMENT OF SIGNIFICANCEGiant lipid vesicles adhering to a solid surface experience strong mechanical stresses. The contacting membrane segment loses thermal fluctuations and accumulates mechanical tension, the equilibration of which can give rise to global shape changes, lipid phase separation, and traction forces. Beyond a threshold tension, vesicles porate, unravel, and spread. Here, we find that a competition from pore-healing can make rupture iterative, rather than a single all-or-nothing event. During burst, single pores expand, spreading a lipid bilayer on the hydrophilic surface and a monolayer on the hydrophobic one. During heal, pore-healing can produce daughter vesicles. This burst-reseal event reiterates “splashing” portions of single vesicles at the solid surface and “bouncing” the remainder as a secondary vesicle in multiple steps.
Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike
Authors: Prévost Jérémie , Gasser Romain , Beaudoin-Bussières Guillaume , Richard Jonathan , Duerr Ralf , Laumaea Annemarie , Anand Sai Priya , Goyette Guillaume , Benlarbi Mehdi , Ding Shilei , Medjahed Halima , Lewin Antoine , Perreault Josée , Tremblay Tony , Gendron-Lepage Gabrielle , Gauthier Nicolas , Carrier Marc , Marcoux Diane , Piché Alain , Lavoie Myriam , Benoit Alexandre , Loungnarath Vilayvong , Brochu Gino , Haddad Elie , Stacey Hannah D. , Miller Matthew S. , Desforges Marc , Talbot Pierre J. , Gould Maule Graham T. , Côté Marceline , Therrien Christian , Serhir Bouchra , Bazin Renée , Roger Michel , Finzi Andrés 
Published: June 2020

ABSTRACTThe SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoprotein of SARS-CoV-2 mediates viral entry and is the main target for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic and public health interventions. Here we performed a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against the SARS-CoV-2 Spike. The vast majority of infected individuals elicited anti-Spike antibodies within 2 weeks after the onset of symptoms. The levels of receptor-binding domain (RBD)-specific IgG persisted overtime, while the levels of anti-RBD IgM decreased after symptoms resolution. Some of the elicited antibodies cross-reacted with other human coronaviruses in a genus-restrictive manner. While most of individuals developed neutralizing antibodies within the first two weeks of infection, the level of neutralizing activity was significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.
High developmental temperature leads to low reproduction despite adult temperature
Authors: Santos Marta A. , Carromeu-Santos Ana , Quina Ana S. , Santos Mauro , Matos Margarida , Simões Pedro 
Published: June 2020

AbstractPhenotypic plasticity can be an important tool in helping organisms to cope with changing thermal conditions and it may show an interdependency between life-stages. For instance, exposure to stressful temperatures during development can trigger a positive plastic response in adults. In this study, we analyse the thermal plastic response of laboratory populations ofDrosophila subobscura, derived from two contrasting latitudes of the European cline. We measured fecundity characters in the experimental populations after exposure to five thermal treatments, with different combinations of developmental and adult temperatures (14°C, 18°C or 26°C). We ask whether (1) adult performance is enhanced (or reduced) by exposing flies to higher (or lower) temperatures during development only; (2) flies raised at lower temperatures outperform those developed at higher ones, supporting the “colder is better” hypothesis; (3) there is a cumulative effect on adult performance of exposing both juveniles and adults to higher (or lower) temperatures; (4) there is any evidence for historical effects on adult performance. Our main findings show that (1) higher developmental temperatures led to low reproductive performance regardless of adult temperature, while at lower temperatures reduced performance only occurred when cold conditions were persistent across juvenile and adult stage; (2) flies raised at lower temperatures did not always outperform those developed at other temperatures; (3) there was no (negative) cumulative effect of exposing both juveniles and adults to higher temperatures; (4) both latitudinal populations showed similar thermal plasticity patterns. The negative effect of high developmental temperature on reproductive performance, regardless of adult temperature, highlights the developmental stage as a critical and most vulnerable stage to climate change and associated heat waves.