bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of cooperation in a yeast population in a public-good driven system
Authors: Raj Namratha , Saini Supreet 
Published: June 2023

AbstractThe phenomenon of cooperation is prevalent at all levels of life. In microbial communities, some groups of cells exhibit cooperative behaviour by producing costly extracellular resources that are freely available to others. These resources are referred to as public goods.Saccharomyces cerevisiae secretes invertase (public good) in the periplasm to hydrolyse sucrose into glucose and fructose, which are further imported by the cells. After hydrolysis of sucrose, the cells retain only 1% of the monosaccharides, while 99% diffuse into the environment and can be utilised by all neighbouring cells. The non-producers of invertase (cheaters) exploit the invertase-producing cells (cooperators) by utilising the monosaccharides and paying nothing for the latter. In this work, we investigate the evolutionary dynamics of this cheater-cooperator system. If cheaters are selected for their higher fitness, the population will collapse. For cooperators to survive cheating and thrive in nature, they should have evolved some survival strategies. To understand the adaptation of cooperators in sucrose, we performed a coevolution experiment in sucrose. Our results show that cooperators increase in fitness as the experiment progresses. This phenomenon was not observed in environments which involved a non-public good system. Genome sequencing reveals the molecular basis for the cooperator adaptating is because of increased privatization of the public-good released carbon resource.
Antigen perception in T cells by long-term Erk and NFAT signaling dynamics
Authors: Wither Matthew J , White William L , Pendyala Sriram , Leanza Paul J , Fowler Doug , Kueh Hao Yuan 
Published: June 2023

ABSTRACTImmune system threat detection hinges on T cells’ ability to perceive varying peptide major-histocompatibility complex (pMHC) antigens. As the Erk and NFAT pathways link T cell receptor engagement to gene regulation, their signaling dynamics may convey information about pMHC inputs. To test this idea, we developed a dual reporter mouse strain and a quantitative imaging assay that, together, enable simultaneous monitoring of Erk and NFAT dynamics in live T cells over day-long timescales as they respond to varying pMHC inputs. Both pathways initially activate uniformly across various pMHC inputs, but diverge only over longer (9+ hrs) timescales, enabling independent encoding of pMHC affinity and dose. These late signaling dynamics are decoded via multiple temporal and combinatorial mechanisms to generate pMHC-specific transcriptional responses. Our findings underscore the importance of long timescale signaling dynamics in antigen perception, and establish a framework for understanding T cell responses under diverse contexts.SIGNIFICANCE STATEMENTTo counter diverse pathogens, T cells mount distinct responses to varying peptide-major histocompatibility complex ligands (pMHCs). They perceive the affinity of pMHCs for the T cell receptor (TCR), which reflects its foreignness, as well as pMHC abundance. By tracking signaling responses in single living cells to different pMHCs, we find that T cells can independently perceive pMHC affinity vs dose, and encode this information through the dynamics of Erk and NFAT signaling pathways downstream of the TCR. These dynamics are jointly decoded by gene regulatory mechanisms to produce pMHC-specific activation responses. Our work reveals how T cells can elicit tailored functional responses to diverse threats and how dysregulation of these responses may lead to immune pathologies.
Efficient Analysis of Proteome-wide FPOP Data by FragPipe
Authors: Ramírez Carolina Rojas , Espino Jessica Arlett , Jones Lisa M. , Polasky Daniel A. , Nesvizhskii Alexey I. 
Published: June 2023

ABSTRACTMonitoring protein structure before and after perturbations can give insights into the role and function of proteins. Fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) allows monitoring of structural rearrangements by exposing proteins to OH radicals that oxidize solvent accessible residues, indicating protein regions undergoing movement. Some of the benefits of FPOP include high throughput and lack of scrambling due to label irreversibility. However, the challenges of processing FPOP data have thus far limited its proteome-scale uses. Here, we present a computational workflow for fast and sensitive analysis of FPOP datasets. Our workflow combines the speed of MSFragger search with a unique hybrid search method to restrict the large search space of FPOP modifications. Together, these features enable more than 10-fold faster FPOP searches that identify 50% more modified peptide spectra than previous methods. We hope this new workflow will increase the accessibility of FPOP to enable more protein structure and function relationships to be explored.
Some like it hot: adaptation to the urban heat island in common dandelion
Authors: Woudstra Yannick , Kraaiveld Ron , Jorritsma Alger , Vijverberg Kitty , Ivanovic Slavica , Erkens Roy , Huber Heidrun , Gravendeel Barbara , Verhoeven Koen J.F. 
Published: June 2023

AbstractThe Urban Heat Island Effect (UHIE) is a globally consistent pressure on species living in cities. Rapid adaptation to the UHIE may be necessary for urban wild flora to persist in cities, but experimental evidence is lacking. Here, we report the first evidence of genetic differentiation in a plant species in response to the UHIE. We collected seeds from common dandelion (Taraxacum officinale) individuals along an urban-rural gradient in the city of Amsterdam (The Netherlands). In common-environment greenhouse experiments, we assessed the effect of elevated temperatures on plant growth and the effect of vernalisation treatments on flowering phenology. We found that urban plants accumulate more biomass at higher temperatures and require shorter vernalisation to induce flowering compared to rural plants. Differentiation was also observed between different intra-urban subhabitats, with park plants displaying a higher vernalisation requirement than street plants. Our results show strong differentiation between urban and rural dandelions in temperature-dependent growth and phenology, consistent with adaptive divergence in response to the UHIE. Rapid adaptation to the UHIE may be a potential explanation for the widespread success of dandelions in urban environments.Summary statementThe urban heat island effect (UHIE) is the most prominent and globally consistent characteristic of environmental change due to urbanisation, severely impacting human populations in cities as well as the cohabiting wildlife. Despite the profoundly mitigating effect of vegetation on urban heat, evidence for plant adaptation to the UHIE has been lacking. Here we provide the first experimental evidence to date, demonstrating adaptation in urban dandelions in response to elevated temperatures, similar to the UHIE. We furthermore show an urban-rural differentiation in flowering response to shorter vernalisation times (cold winter period to activate the onset of flowering in early spring). Given the predominantly asexual apomictic mode of reproduction in dandelions, this evolution is likely the result of environmental filtering on a diverse population of clonal genotypes. We conclude that plant adaptation to the UHIE exists and recommend future studies to contrast our findings with those in outcrossing sexual plant systems. Studies of urban heat adaptation can bring impactful contributions to building climate change-resilient environments and plants should be an integral part of this research.
ADrosophilamodel of chemotherapy-related cognitive impairment
Authors: Torre Matthew , Bukhari Hassan , Nithianandam Vanitha , Zanella Camila A , Mata Douglas A , Feany Mel B 
Published: June 2023

AbstractChemotherapy-related cognitive impairment (CRCI) is a common adverse effect of treatment and is characterized by deficits involving multiple cognitive domains including memory. Despite the significant morbidity of CRCI and the expected increase in cancer survivors over the coming decades, the pathophysiology of CRCI remains incompletely understood, highlighting the need for new model systems to study CRCI. Given the powerful array of genetic approaches and facile high throughput screening ability in Drosophila, our goal was to validate aDrosophilamodel of CRCI. We administered the chemotherapeutic agents cisplatin, cyclophosphamide, and doxorubicin to adult Drosophila. Neurocognitive deficits were observed with all tested chemotherapies, especially cisplatin. We then performed histologic and immunohistochemical analysis of cisplatin-treatedDrosophilatissue, demonstrating neuropathologic evidence of increased neurodegeneration, DNA damage, and oxidative stress. Thus, ourDrosophilamodel of CRCI recapitulates clinical, radiologic, and histologic alterations reported in chemotherapy patients. Our newDrosophilamodel can be used for mechanistic dissection of pathways contributing to CRCI and pharmacologic screens to identify novel therapies to ameliorate CRCI.Summary StatementWe present aDrosophilamodel of chemotherapy-related cognitive impairment, which recapitulates neurocognitive and neuropathologic changes observed in cancer patients treated with chemotherapy.
Comparative B cell and antibody responses induced by adenoviral vectored and mRNA vaccines against COVID-19
Authors: Liu Yi , Sánchez-Ovando Stephany , Carolan Louise , Dowson Leslie , Khvorov Arseniy , Hadiprodjo Jessica , Tseng Yeu Yang , Delahunty Catherine , Khatami Ameneh , Macnish Marion , Dougherty Sonia , Hagenauer Michelle , Riley Kathryn E. , Jadhav Ajay , Harvey Joanne , Kaiser Marti , Mathew Suja , Hodgson David , Leung Vivian , Subbarao Kanta , Cheng Allen C. , Macartney Kristine , Koirala Archana , Marshall Helen , Clark Julia , Blyth Christopher C. , Wark Peter , Kucharski Adam J. , Sullivan Sheena G. , Fox Annette 
Published: June 2023

AbstractBoth vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. However, adenoviral vectored (AdV) vaccines may be less immunogenic than mRNA vaccines against SARS-CoV-2. We assessed anti-spike and anti-vector immunity among infection-naïve Health Care Workers (HCW) following two doses of AdV (AZD1222) versus mRNA (BNT162b2) vaccine. 183 AdV and 274 mRNA vaccinees enrolled between April and October 2021. Median ages were 42 and 39 years, respectively. Blood was collected at least once, 10-48 days after vaccine dose 2. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p<0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human Adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine due to greater B cell expansion and targeting of the RBD. Pre-existing AdV vector cross-reactive antibodies were boosted following AdV vaccination but had no detectable effect on immunogenicity.Key pointsmRNA SARS-CoV-2 vaccine induced higher surrogate neutralizing antibody titres than adenoviral vaccinemRNA vaccine induced a more potent, RBD-targeted B cell response than AdV vaccineAdenoviral vaccine boosted antibodies against human Adenovirus, but titres don’t correlate with anti-spike titres
Racial Differences in Associations Between Adverse Childhood Experiences and Physical, Mental, and Behavioral Health
Authors: Lam-Hine Tracy , Riddell Corinne A. , Bradshaw Patrick T. , Omi Michael , Allen Amani M. 
Published: June 2023

AbstractIntroductionAdverse childhood experiences (ACEs) are associated with poor adulthood health, with individuals experiencing multiple ACEs at greatest risk. Multiracial people have high mean ACEs scores and elevated risk of several outcomes, but are infrequently the focus of health equity research. This study aimed to determine whether this group should be targeted for prevention efforts.MethodsWe analyzed Waves 1 (1994-95), 3 (2001-02), and 4 (2008-09) of the National Longitudinal Study of Adolescent to Adult Health (n = 12,372) in 2023, estimating associations between four or more ACEs and physical (metabolic syndrome, hypertension, asthma), mental (anxiety, depression), and behavioral (suicidal ideation, drug use) outcomes. We estimated risk ratios for each outcome in modified Poisson models with a race × ACEs interaction, adjusted for hypothesized confounders of the ACE-outcome relationships. We used the interaction contrast to estimate excess cases per 1,000 individuals for each group relative to Multiracial participants.ResultsExcess case estimates of asthma were significantly smaller for White (−123 cases, 95% CI: -251, -4), Black (−141, 95% CI: -285, -6), and Asian (−169, 95% CI: -334, -7) participants compared to Multiracial participants. Black (−100, 95% CI: -189, -10), Asian (−163, 95% CI: -247, -79) and Indigenous (−144, 95% CI: -252, -42) participants had significantly fewer excess cases of and weaker (p < 0.001) relative scale association with anxiety compared to Multiracial participants.ConclusionsAdjusted associations between ACEs and asthma or anxiety appear stronger for Multiracial people than other groups. ACEs are universally harmful but may contribute disproportionately to morbidity in this population.
Social, environmental and economic risk factors and determinants of sleep disturbances in Latin America: A systematic review and a meta-analysis of public health literature
Authors: Etindele Sosso Faustin Armel , Torres Silva Filipa , Queiroz Rodrigues Rita , Carvalho Margarida , Zoukal Sofia , Cordova Zarate Gabriel 
Published: June 2023

AbstractBackgroundMental health recovery is associated with healthy sleep, and disturbances of both, areas represent an increasing public health issue worldwide, particularly in Latin America. Among multiple determinants affecting sleep health, individual’s socioeconomic status (SES) is the most ignored and underestimated through literature. No systematic review on the relation between SES and sleep health has been previously conducted in Latin America.MethodsPRISMA guidelines were used.ResultsTwenty cross-sectional studies were selected. 80,0% (n=16) were performed in Brazil, 10,0% (n=2) in Peru, 5,0% (n=1) in Chile, and 5,0% (n=1) were multicentric (11 countries). The combined total number of participants were N=128455, being 3,7% (n= 4693) children, 16,0% (n= 20586) adolescents and 80,3% (n=103176) adults. Higher SES was associated with lower sleep duration. Lower SES was associated with a decrease in sleep quality. Excessive Daytime Sleepiness (EDS) was significantly more prevalent in individuals with lower family income and less education. Sleep bruxism was associated with higher education and lower SES was associated with more sleep bruxism. A meta-analysis of random effects model showed that pooled prevalence of sleep disturbances was 27.32 % (95 % CI 21.71–33.75) with high heterogeneity (I2= 100 %). Pooled prevalence decreased with high education (OR 0.83; 95%CI [0.75-0.91]; I2= 79%), while it increased by low income (OR 1.26; 95%CI [1.12-1.42]; I2= 59%), unemployment (OR 2.84; 95%CI [2.14-3.76]; I2= 0%) or being housewife (OR 1.72; 95%CI [1.19-2.48]; I2=55.4%).DiscussionGradient of health disparity existing for some diseases like cardiovascular illness, seems the same for sleep disturbances regardless of world region. Therefore, sleep disturbances management should be address in a multidimensional approach with a significant investment of government in targeted public health program, to reduce sleep disparities and support research before the situation become uncontrollable.
Stabilisation of soil organic matter with rock dust partially counteracted by plants
Authors: Buss Wolfram , Hasemer Heath , Ferguson Scott , Borevitz Justin 
Published: June 2023

AbstractSoil application of Ca– and Mg-rich silicates can capture and store atmospheric carbon dioxide as inorganic carbon but could also have the potential to stabilise soil organic matter (SOM). Synergies between these two processes have not been investigated. Here, we apply finely ground silicate rock mining residues (basalt and granite blend) to a loamy sand in a pot trial at a rate of 4% (equivalent to 50 t ha-1) and investigate the effects of a wheat plant and two watering regimes on soil carbon sequestration. Rock dust addition increased soil pH, electric conductivity and soil-exchangeable Ca and Mg contents, as expected for weathering, but decreased exchangeable levels of micronutrients Mn and Zn, likely related to soil pH. Importantly, it increased mineral-associated organic matter by 22% due to the supply of secondary minerals and associated sites for SOM sorption. Additionally, in the non-planted treatments, rock supply of Ca and Mg increased soil microaggregation that subsequently stabilised labile particulate organic matter as organic matter occluded in aggregates by 46%. Plants, however, reduced soil exchangeable Mg and Ca contents and hence counteracted the silicate rock effect on microaggregates and carbon within. We attribute this cation loss to plant exudates released to solubilise micronutrients and hence neutralise plant deficiencies. The effect of enhanced silicate rock weathering on SOM stabilisation could substantially boost its carbon sequestration potential when pH and micronutrient effects are considered.
A metabolic crosstalk between liposarcoma and muscle sustains tumor growth
Authors: Gabrielle Manteaux , Jaime Prieto Romero , Laurie Gayte , Blanche Riquier-Morcant , Alix Amsel , Solenn Jacq , Madi Y Cisse , Gaelle Perrot , Frédéric Chibon , Pascal Pomies , Sebastien Carrere , Nelly Firmin , Romain Riscal , Laetitia K Linares 
Published: June 2023

AbstractDedifferentiated (DD-LPS) and Well-differentiated (WD-LPS) liposarcoma are characterized by a systematic amplification of theMDM2oncogene. We recently demonstrated that p53-independent metabolic functions of chromatin-bound MDM2 (C-MDM2) are exacerbated in LPS and mediate an addiction to serine metabolism in order to sustain tumor growth. Here, we show that metabolic cooperation between LPS and distant muscle, which raise serine and glycine blood levels, is essential for LPS tumor growth. By releasing IL-6, tumor influence distant muscle to upregulate their serine synthesis machinery. Blocking IL-6 secretion or treating LPS cells with FDA approved IL-6 inhibitor, decreased serine production and impaired tumor proliferation. These data reveal IL-6 as a central tumorkine in metabolic crosstalk between tissues and identifies IL-6 as a plausible treatment for LPS patients.
Engineering ligand stabilized aquaporin reporters for magnetic resonance imaging
Authors: Yun Jason , Baldini Logan , Huang Yimeng , Li Eugene , Li Honghao , Chacko Asish N. , Miller Austin D.C. , Wan Jinyang , Mukherjee Arnab 
Published: June 2023

ABSTRACTImaging transgene expression in live tissues requires reporters that are detectable with deeply penetrant modalities, such as magnetic resonance imaging (MRI). Here, we show that LSAqp1, a water channel engineered from aquaporin-1, can be used to create background-free, drug-gated, and multiplex images of gene expression using MRI. LSAqp1 is a fusion protein composed of aquaporin-1 and a degradation tag that is sensitive to a cell-permeable ligand, which allows for dynamic small molecule modulation of MRI signals. LSAqp1 improves specificity for imaging gene expression by allowing reporter signals to be conditionally activated and distinguished from the tissue background by difference imaging. In addition, by engineering destabilized aquaporin-1 variants with different ligand requirements, it is possible to image distinct cell types simultaneously. Finally, we expressed LSAqp1 in a tumor model and showed successful in vivo imaging of gene expression without background activity. LSAqp1 provides a conceptually unique approach to accurately measure gene expression in living organisms by combining the physics of water diffusion and biotechnology tools to control protein stability.
Identification of non-conventional small molecule degraders and stabilizers of squalene synthase
Authors: Hoock Joseph , Rossetti Cecilia , Bilgin Mesut , Depta Laura , Enemark-Rasmussen Kasper , Christianson John C. , Laraia Luca 
Published: June 2023

AbstractGraphical abstractSqualene synthase (SQS) is an essential enzyme in the mevalonate pathway whose abundance and activity control cholesterol biosynthesis and homeostasis. Although catalytic inhibitors of SQS have been developed to attenuate cholesterol, none so far have been approved for therapeutic use. Herein we sought to develop SQS degraders using targeted protein degradation (TPD) as an approach to lower overall cellular cholesterol content. We found that KY02111, a small molecule ligand of SQS, could selectively cause SQS to degrade in a proteasome-dependent manner. In contrast, compounds based on the same scaffold linked to E3 ligase recruiting ligands led to SQS stabilization. Whole cell proteomic analysis found KY02111 to reduce only the levels of SQS, while lipidomic analysis determined that KY02111 treatment concomitantly reduced cellular cholesteryl ester content. SQS stabilizers were shown to shield SQS from its natural turnover without recruiting their matching E3 ligase. Our work shows that degradation of SQS is possible despite a challenging biological setting and lays the groundwork for future development of either SQS degrading or stabilizing probes.