bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring natural odour landscapes: A case study with implications for human-biting insects
Authors: Zung Jessica L. , Kotb Sumer M. , McBride Carolyn S. 
Published: May 2023

AbstractThe natural world is full of odours—blends of volatile chemicals emitted by potential sources of food, social partners, predators, and pathogens. Animals rely heavily on these signals for survival and reproduction. Yet we remain remarkably ignorant of the composition of the chemical world. How many compounds do natural odours typically contain? How often are those compounds shared across stimuli? What are the best statistical strategies for discrimination? Answering these questions will deliver crucial insight into how brains can most efficiently encode olfactory information. Here, we undertake the first large-scale survey of vertebrate body odours, a set of stimuli relevant to blood- feeding arthropods. We quantitatively characterize the odour of 64 vertebrate species (mostly mammals), representing 29 families and 13 orders. We confirm that these stimuli are complex blends of relatively common, shared compounds and show that they are much less likely to contain unique components than are floral odours—a finding with implications for olfactory coding in blood feeders and floral visitors. We also find that vertebrate body odours carry little phylogenetic information, yet show consistency within a species. Human odour is especially unique, even compared to the odour of other great apes. Finally, we use our newfound understanding of odour-space statistics to make specific predictions about olfactory coding, which align with known features of mosquito olfactory systems. Our work provides one of the first quantitative descriptions of a natural odour space and demonstrates how understanding the statistics of sensory environments can provide novel insight into sensory coding and evolution.
Mutualism reduces the severity of gene disruptions in predictable ways across microbial communities
Authors: Martinson Jonathan N. V. , Chacón Jeremy M. , Smith Brian A. , Villarreal Alex R. , Hunter Ryan C. , Harcombe William R. 
Published: May 2023

AbstractPredicting evolution in microbial communities is critical for problems from human health to global nutrient cycling. Understanding how species interactions impact the distribution of fitness effects for a focal population would enhance our ability to predict evolution. Specifically, it would be useful to know if the type of ecological interaction, such as mutualism or competition, changes the average effect of a mutation (i.e., the mean of the distribution of fitness effects). Furthermore, how often does increasing community complexity alter the impact of species interactions on mutant fitness? To address these questions, we created a transposon mutant library inSalmonella entericaand measured the fitness of loss of function mutations in 3,550 genes when grown alone versus competitive co-culture or mutualistic co-culture withEscherichia coliandMethylorubrum extorquens.We found that mutualism reduces the average impact of mutations, while competition had no effect. Additionally, mutant fitness in the 3-species communities can be predicted by averaging the fitness in each 2-species community. Finally, the fitness effects of several knockouts in the mutualistic communities were surprising. We discovered thatS. entericais obtaining a different source of carbon and more vitamins and amino acids than we had expected. Our results suggest that species interactions can predictably impact fitness effect distributions, in turn suggesting that evolution may ultimately be predictable in multi-species communities.
Electrophysiological hallmarks for event relations and event roles in working memory
Authors: Yu Xinchi , Li Jialu , Zhu Hao , Tian Xing , Lau Ellen 
Published: May 2023

AbstractThe ability to maintain events (i.e. interactions between/among objects) in working memory is crucial for our everyday cognition, yet the format of this representation is poorly understood. The current ERP study was designed to answer two questions: How is maintaining events (e.g., the tiger hit the lion) neurally different from maintaining item coordinations (e.g., the tiger and the lion)? That is, how is the event relation (present in events but not coordinations) represented? And how is the agent, or initiator of the event encoded differently from the patient, or receiver of the event during maintenance? We used a novel picture-sentence match-across-delay approach in which the working memory representation was ‘pinged’ during the delay, in two ERP experiments with Chinese and English materials. First, we found that maintenance of events elicited a long-lasting late sustained difference in posterior-occipital electrodes relative to non-events. This effect resembled the negative slow wave reported in previous studies of working memory, suggesting that the maintenance of events in working memory may impose a higher cost compared to coordinations. Second, in order to elicit a hallmark for agent vs. patient representation in working memory, we pinged agent or patient characters during the delay. Although planned comparisons did not reveal significant differences in the ERPs elicited by the agent pings vs. patient pings, we found that the ping appeared to dampen the ongoing sustained difference, suggesting a shift from sustained activity to activity silent mechanisms. These results represent one of the uses of ERPs to elucidates the format of neural representation for events in working memory.
A Mechanism Underpinning the Bioenergetic Metabolism-Regulating Function of Gold Nanocatalysts
Authors: Wang Zixin , Henriques Alexandre , Rouvière Laura , Callizot Noëlle , Tan Lin , Hotchkin Michael T. , Rossignol Rodrigue , Mortenson Mark G. , Ho Karen S. , Wang Hui 
Published: May 2023

ABSTRACTBioenergetic deficits, such as mitochondrial impairments and dysfunction in glucose metabolism, have been identified as significant contributors to neurodegenerative diseases. Nevertheless, identifying safe and effective means to address intracellular bioenergetic deficits remains a significant challenge. This work provides mechanistic insights into the bioenergetic metabolism-regulating function of a suspension of gold (Au) nanocrystals, referred to as CNM-Au8®, that are synthesized electrochemically in the absence of any surface-capping organic ligands. When neurons are subjected to excitotoxic stressors or toxic peptides, treatment of neurons with CNM-Au8 results in dose-dependent neuronal survival and preservation of neurite networks across multiple neuronal subtypes. CNM-Au8 efficiently catalyzes the conversion of an energetic co-factor, nicotinamide adenine dinucleotide hydride (NADH), into its oxidized, dehydrogenated counterpart (NAD+), which triggers an increase in energy production in the form of adenosine triphosphate (ATP). Detailed kinetic measurements reveal that CNM-Au8-catalyzed NADH oxidation obeys Michaelis-Menten kinetics and exhibits pH-dependent kinetic profiles. CNM-Au8 functions as an NADH-dehydrogenase-mimicking nanozyme that effectively regulates intracellular bioenergetic metabolism. We further utilize photoexcited charge carriers and photothermal transduction, which can be generated through optical excitations of the plasmonic electron oscillations or the interband electronic transitions in CNM-Au8, as unique leverages to modulate reaction kinetics. Benefiting from their bio-compatibility, blood-brain barrier penetrance, tunable optical properties, and enzyme-mimicking functions, CNM-Au8 nanocrystals with deliberately tailored structures and surfactant-free clean surfaces hold great promise for developing next-generation therapeutic agents for neurodegenerative diseases.
Structural and functional damage to neuronal nuclei caused by extracellular tau oligomers
Authors: Sun Xuehan , Eastman Guillermo , Shi Yu , Saibaba Subhi , Oliveira Ana K. , Lukens John R. , Norambuena Andrés , Mandell James W. , Bloom George S. 
Published: May 2023

ABSTRACTINTRODUCTIONNeuronal nuclei are normally smoothly surfaced. In Alzheimer’s disease (AD) and other tauopathies, though, they often develop invaginations. We investigated mechanisms and functional consequences of neuronal nuclear invagination in tauopathies.METHODSNuclear invagination was assayed by immunofluorescence in brain, and in cultured neurons before and after extracellular tau oligomers (xcTauO) exposure. Nucleocytoplasmic transport was assayed in cultured neurons. Gene expression was investigated using nanoString nCounter technology and qRT-PCR.RESULTSInvaginated nuclei were twice as abundant in human AD as in cognitively normal adults, and were increased in mouse neurodegeneration models. In cultured neurons, nuclear invagination was induced by xcTauOs by an intracellular tau-dependent mechanism. xcTauOs impaired nucleocytoplasmic transport, increased histone H3 trimethylation at lysine 9 and altered gene expression, especially by increasing tau mRNA.DISCUSSIONxcTauOs may be a primary cause of nuclear invaginationin vivo, and by extension, impair nucleocytoplasmic transport and induce pathogenic gene expression changes.
Dehydration stress and Mayaro virus vector competence inAedes aegypti
Authors: Manzano-Alvarez Jaime , Terradas Gerard , Holmes Christopher J. , Benoit Joshua B. , Rasgon Jason L. 
Published: May 2023

AbstractThe mosquitoAedes aegyptiis a competent vector of multiple pathogens including dengue, Zika, yellow fever, chikungunya, and Mayaro viruses.Ae. aegyptiis highly invasive and is currently present in the Americas, Oceania, Asia, and Europe, but its distribution and the pathogens it transmits are expected to change due to climate change. Relative humidity is an environmental variable that affects mosquito biology and distribution and can differ between location, habitat, and season, with mosquitoes facing significant variation in relative humidity during their lifespan. Low relative humidity can induce dehydration in mosquitoes, leading to alterations in physiological and behavioral responses relevant for pathogen transmission such as bloodfeeding and host-seeking behavior. In this study, we evaluated the short and long-term effects of dehydration stress on mortality and Mayaro virus vector competence in Ae. aegypti. Our results show that exposure to dehydration does not impact viral titers, nor infection, dissemination and transmission rates, in mosquitoes infected with Mayaro virus. However, we detected a significant effect of dehydration on mosquito mortality and blood feeding frequency regardless of infection status. The previously observed effects of higher feeding during dehydration and the current observation of altered survival along with no impact on vector competence suggest that the impact of dehydration on viral transmission in mosquitoes will likely be complex.
Lipid transfer proteins and a PI 4-kinase initiate nuclear phosphoinositide signaling
Authors: Carrillo Noah D. , Chen Mo , Wen Tianmu , Awasthi Poorwa , Wolfe Trevor J. , Sterling Colin , Cryns Vincent L. , Anderson Richard A. 
Published: May 2023

SummaryPhosphoinositide (PIPn) messengers are present in non-membranous regions of nuclei, where they are assembled into a phosphatidylinositol (PI) 3-kinase (PI3K)/Akt pathway that is distinct from the cytosolic membrane-localized pathway. In the nuclear pathway, PI kinases/phosphatases bind the p53 tumor suppressor protein (wild-type and mutant) to generate p53-PIPncomplexes that regulate Akt activation. However, this pathway is dependent on poorly characterized nuclear PIPnpools. Here we report that PI transfer proteins (PITPs), which transport PI between membranes to enable membrane-localized PIPnsynthesis, accumulate in the nucleoplasm in response to stress and supply nuclear PIPnpools. PITPα/β and the PI 4-kinase PI4KIIα bind p53 and are required to generate p53-PI4P, which is further phosphorylated to synthesize p53-PIPncomplexes that regulate nuclear Akt activation and stress-resistance. Remarkably, PITPα/β and PI4KIIα initiate PIPn-linkage to multiple proteins that are detectable by immunoblotting and [3H]myo-inositol metabolic labeling and are resistant to denaturation, suggesting a posttranslational modification.In briefPhosphatidylinositol transfer proteins initiate the nuclear PIPn-linked protein network in membrane-free regions.
Skin in The Game: The Cost Consequences of Skin Cancer Diagnosis, Treatment and Care in Northern Ireland
Authors: McFerran Ethna , Donaldson Sarah , Lawler Mark 
Published: May 2023

AbstractBackgroundSkin cancer is a prevalent type of cancer in the UK. Its rising incidence and mortality rates are expected to result in substantial financial implications, particularly on diagnostic and treatment services for skin cancer management in Northern Ireland. Such anticipated disease increases underscore the need for prevention and control measures that should guide policymaking and planning efforts.MethodsWe conducted a retrospective cost study to measure the burden of skin cancer in Northern Ireland from a healthcare system perspective. Our data-driven model utilized bottom-up methodology1,2and reported 2018 costs using NHS reference unit costs (UK£) for skin cancer diagnosis and treatment patient pathways. Sensitivity analyses were performed, including varying diagnostic volumes by applying multipliers for benign cases and assuming a diagnostic conversion rate of 6.8%. An alternative chemotherapy regimen compliance rate was also examined at 75% as compared to base case. Proportional increases were projected based on future estimated increases of 9% and 28% in melanoma cases for diagnostic, treatment, and follow-up volumes specifically related to malignant melanoma.ResultsAs of 2018, NICR recorded 4142 non-melanoma skin cancers (NMSC) and 423 malignant melanoma (MM) cases, averaging 17.5 new patients per trust weekly. The total costs for managing NMSC was £1,815,936, whereas that for MM skin cancer costs was £12,364,220, out of which £8,792,208 accounted for procurement, administration, and chemotherapy drug use. Healthcare providers spent a total of £17,024,115 on skin cancer care. Sensitivity analysis suggest diagnostic cost would either reduce by £781k to £3,061,524 or increase significantly to £11,212,183 based on referral volume assumptions. If base case rates rise by 9 or 28% estimated total costs of treating skin cancer will increase to £18.1 million and £20.4 million respectively.ConclusionsSkin cancer management costs in Northern Ireland vary from ∼£14.3m to £26.2m depending on diagnostic referral assumptions. Malignant melanoma costs have risen ∼10 fold over the past decade mainly due to chemotherapy costs. Predicted 28% increase in melanoma cases by 2040 would lead to £3.3m of additional referral, diagnostic and treatment expenditures, which with inflation adjustment to a further budget requirement of approximately £6.4 million by 2022 rates.
Transcription-Coupled Repair of DNA Interstrand Crosslinks by UVSSA
Authors: Liebau Rowyn C , Waters Crystal , Ahmed Arooba , Soni Rajesh K , Gautier Jean 
Published: May 2023

SummaryDNA interstrand crosslinks (ICLs) are covalent bonds between bases on opposing strands of the DNA helix which prevent DNA melting and subsequent DNA replication or RNA transcription. Here, we show that Ultraviolet Stimulated Scaffold Protein A (UVSSA) participates in transcription-coupled repair of ICLs in human cells. Inactivation of UVSSA sensitizes human cells to ICL-inducing drugs, and delays ICL repair. UVSSA is required for transcription-coupled repair of a single ICL in a fluorescence- based reporter assay. UVSSA localizes to chromatin following ICL damage, and interacts with transcribing Pol II, CSA, CSB, and TFIIH. Specifically, UVSSA interaction with TFIIH is required for ICL repair. Finally, UVSSA expression positively correlates with ICL chemotherapy resistance in human cancer cell lines. Our data strongly suggest that transcription-coupled ICL repair (TC-ICR) is abona fideICL repair mechanism that contributes to crosslinker drug resistance independently of replication-coupled ICL repair.
A wound-induced differentiation trajectory for neurons
Authors: Hulett Ryan E. , Gehrke Andrew R. , Gompers Annika , Rivera-López Carlos , Srivastava Mansi 
Published: May 2023

AbstractAnimals capable of whole-body regeneration can replace any missing cell type and regenerate fully-functional new organs,de novo. The regeneration of a new brain requires the formation of diverse neuronal cell types and their assembly into an organized structure and correctly-wired circuits. Recent work in various regenerative animals has revealed transcriptional programs required for the differentiation of distinct neuronal subpopulations, however how these transcriptional programs are initiated upon amputation remains unknown. Here, we focused on the highly regenerative acoel worm,Hofstenia miamia, to study wound-induced transcriptional regulatory events that lead to the production of neurons. Footprinting analysis using chromatin accessibility data on an improved genome assembly revealed that binding sites for the NFY transcription factor complex were significantly bound during regeneration, showing a dynamic increase in binding within one hour upon amputation specifically in tail fragments, which will regenerate a new brain. Strikingly, NFY targets were highly enriched for genes with neuronal functional. Single-cell transcriptome analysis combined with functional studies identifiedsox4+stem cells as the likely progenitor population for multiple neuronal subtypes. Further, we found that wound-inducedsox4expression is likely under direct transcriptional control by NFY, uncovering a mechanism for how early wound-induced binding of a transcriptional regulator results in the initiation of a neuronal differentiation pathway.HighlightsA new chromosome-scale assembly forHofsteniaenables comprehensive analysis of transcription factor binding during regenerationNFY motifs become dynamically bound by 1hpa in regenerating tail fragments, particularly in the loci of neural genesAsox4+neural-specialized stem cell is identified using scRNA-seqsox4is wound-induced and required for differentiation of multiple neural cell typesNFY regulates wound-induced expression ofsox4during regeneration
Trends in congenital clubfoot prevalence and co-occurring anomalies during 1994-2021 in Denmark: A nationwide register-based study of 1,315,282 live born infants
Authors: Hedley Paula L. , Lausten-Thomsen Ulrik , Conway Kristin M. , Hindsø Klaus , Romitti Paul A. , Christiansen Michael 
Published: May 2023

AbstractBackgroundCongenital talipes equinovarus (clubfoot) is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. Herein, we used publicly available data to ascertain liveborn infants with clubfoot delivered in Denmark during 1994–2021, and to classify co-occurring congenital anomalies, estimate annual prevalence, and compare clubfoot occurrence with maternal smoking rates, a commonly reported risk factor. Characterizing this nationwide, liveborn cohort provides a population-based resource for etiopathogenic investigations and life course surveillance.MethodsThis case-cohort study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,315,282 liveborn infants delivered during 1994–2021 in Denmark to Danish parents. Among these, 2,358 infants (65.1% male) were ascertained with clubfoot and classified as syndromic (co-occurring chromosomal, genetic, or teratogenic syndromes) and nonsyndromic (isolated or co-occurring multiple congenital anomalies [MCA]). Annual prevalence estimates and corresponding 95% confidence intervals (CIs) for children with nonsyndromic clubfoot were estimated using Poisson regression and compared with population-based, maternal annual smoking rates obtained from publicly available resources.ResultsInfants most often presented with nonsyndromic clubfoot (isolated=84.6%; MCA=10.9%); limb and heart anomalies were the most frequently identified MCAs. Prevalence (per 1,000 liveborn infants) was 1.52 (CI 1.45 – 1.58) for isolated and 0.19 (CI 0.17 – 0.22) for MCA clubfoot. Prevalence estimates for both isolated and MCA clubfoot remained relatively stable during the study period, despite marked decreases in population-based maternal smoking rates.ConclusionsFrom 1994-2021, prevalence of nonsyndromic clubfoot in Denmark was relatively stable. Reduction in population-level maternal smoking rates did not seem to impact prevalence estimates, providing some support for the suspected multifactorial etiopathogenesis of this anomaly. This nationwide, liveborn cohort, ascertained and clinically characterized using publicly available data from the Danish Biobank Register, provides a population-based clinical and biological resource for future etiopathogenic investigations and life course surveillance.
Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons
Authors: Kochan Sandra M.V. , Malo Meret Cepero , Jevtic Milica , Jahn Hannah M. , Wani Gulzar A. , Gaedke Felix , Schäffner Iris , Chichung-Lie Dieter , Schauss Astrid , Bergami Matteo 
Published: May 2023

AbstractIntegration of new neurons into adult hippocampal circuits is a process coordinated by local and long-range synaptic inputs. To achieve stable integration and uniquely contribute to hippocampal function, immature neurons are endowed with a critical period of heightened synaptic plasticity, yet it remains unclear which mechanisms sustain this form of plasticity during neuronal maturation. We found that, as new neurons enter their critical period, a transient surge in fusion dynamics stabilizes elongated mitochondrial morphologies in dendrites to fuel synaptic plasticity. Conditional ablation of fusion dynamics to prevent mitochondrial elongation selectively impaired spine plasticity and synaptic potentiation, disrupting neuronal competition for stable circuit integration, ultimately leading to decreased survival. Despite profuse mitochondrial fragmentation, manipulation of competition dynamics was sufficient to restore neuronal survival, but left neurons poorly responsive to experiences at the circuit level. Thus, by enabling synaptic plasticity during the critical period, mitochondrial fusion facilitates circuit remodeling by adult-born neurons.