bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and factors associated with incompletion of measles and rubella vaccine routine immunization among children aged 18-59 months in Kilimanjaro region, Tanzania
Authors: Gichogo David M. , Mbezi Abdul A. , Sasi Sasi K. , Magogo Vailet , Shewiyo Edwin J. , Nkenguye William , Tinuga Florian , Msuya Sia E. 
Published: July 2024

ABSTRACTBackgroundIn Tanzania Measles and Rubella (MR) vaccination coverage of 90% in 90% of the regions was achieved in 2018. However, there are councils lagging in MR1 coverage, 38 (19%) councils out of 195 had <90% coverage by the end of 2019 while MR2 coverage is struggling with 99 (51%) of councils having a coverage of <90% at the end of 2019. Kilimanjaro region is among the regions with some councils having MR coverage of <80%. There is a need for information on why a significant proportion of eligible children are not receiving the second dose of MR vaccine.ObjectiveTo determine prevalence and factors associated with incompletion of MR vaccination among children aged 18-59 months in two districts of Kilimanjaro region.MethodologyThis study was a cross-sectional study conducted in Moshi urban and rural councils, two out of the seven councils in Kilimanjaro region. The study population was children aged 18-59 months whose parents/ caregivers have been the residents of the respective districts for at least 3 past years. Interviews using questionnaires were used for data collection. Data was entered and analyzed using SPSS version 20.ResultsA total of 415 children aged 18-59 months were enrolled. The proportion of children with incomplete MR2 vaccination was 14.2%. Only 33% of the 415 caregivers knew MR vaccine is given at 9 and 18 months and 24% reported unavailability of vaccine at their scheduled visit. Children from Moshi rural council (AOR=2.53, 95% CI =1.36-4.73) had higher odds of MR incompletion. Lower odds of MR vaccine incompletion were among caregivers who were aware on the time for MR vaccination; 9 and 18 months (AOR=0.27, 95% CI=0.10-0.73), caregivers who had knowledge that MR vaccine protects measles, and those who had health promotion talk on the vaccination day.ConclusionNearly one in ten (14.2%) children do not complete the recommended two doses of MR vaccines. Strategies to improve awareness and knowledge on timing, frequency and advantage of MR and other vaccines is needed among parents/ caregivers in this setting. Further, improvement in ordering and supply of vaccines at health facilities needs to be improved.
Variation in albumin glycation rates in birds suggests resistance to relative hyperglycaemia rather than conformity to the pace of life syndrome hypothesis
Authors: Moreno-Borrallo Adrián , Jaramillo-Ortiz Sarahi , Schaeffer-Reiss Christine , Quintard Benoît , Rey Benjamin , Bize Pierre , Viblanc Vincent A. , Boulinier Thierry , Chastel Olivier , Gutiérrez Jorge S. , Masero Jose A. , Bertile Fabrice , Criscuolo François 
Published: July 2024

AbstractThe pace of life syndrome hypothesis (POLS) suggests that organisms’ life history, physiological and behavioural traits should co-evolve. In this framework, how glycaemia (i.e., blood glucose levels) and its reaction with proteins and other compounds (i.e. glycation) covary with life history traits remain relatively under-investigated, despite the well documented consequences of glucose and glycation on ageing, and therefore potentially on life history evolution. Birds are particularly relevant in this context given that they have the highest blood glucose levels within vertebrates and still higher mass-adjusted longevity when compared to organisms with similar physiology as mammals. We thus performed a comparative analysis on glucose and albumin glycation rates of 88 bird species from 22 orders, in relation to life history traits (body mass, clutch mass, maximum lifespan and developmental time) and diet. Glucose levels correlated positively with albumin glycation rates in a non-linear fashion, suggesting resistance to glycation in species with higher glucose levels. Plasma glucose levels decreased with increasing body mass but, contrary to what is predicted to the POLS hypothesis, glucose levels increased with maximum lifespan before reaching a plateau. Finally, terrestrial carnivores showed higher albumin glycation compared to omnivores despite not showing higher glucose, which we discuss may be related to additional factors as differential antioxidant levels or dietary composition in terms of fibres or polyunsaturated fatty acids. These results increase our knowledge about the diversity of glycaemia and glycation patterns across birds, pointing towards the existence of glycation resistance mechanisms within comparatively high glycaemic birds.
Poly(ADP-ribose) binding sites on collagen I fibrils for nucleating intrafibrillar bone mineral
Authors: Zecca Marco A. , Greer Heather F. , Duer Melinda J. 
Published: July 2024

AbstractBone calcification is essential for vertebrate life. The mechanism by which mineral ions are transported into collagen fibrils to induce intrafibrillar mineral formation requires a calcium binding biopolymer that also has highly selective binding to the collagen fibril hole zones where intrafibrillar calcification begins, over other bone extracellular matrix components. Poly(ADP-ribose) has been shown to be a candidate biopolymer for this process and we show here that poly(ADP-ribose) has high affinity, highly conserved binding sites in the collagen type I C-terminal telopeptides. The discovery of these poly(ADP-ribose)-collagen binding sites gives new insights into the chemical mechanisms underlying bone calcification and possible mechanisms behind pathologies where there is dysfunctional bone calcification.
HIF-1 activated by PIM1 assembles a pathological transcription complex and regulon that drives JAK2V617F MPN disease
Authors: Kealy David , Ellerington Ruth , Bansal Suraj , Zeng Andy G.X. , Medeiros Jessie J.F. , West Katie A. , Blacknell Nicole-Mae , Hawley Catherine A. , Lukaszonek Jakub , Gawne Richard T. , Khoo Hwei Minn , Caalim Gillian , Drylie Bryce , Chatzigerou Jenny , Ferreira Bianca Lima , Fielding Adele K , Wang Guanlin , Kent David G. , Psaila Bethan , Wilkinson Adam C. , Holding Andrew N. , Hitchcock Ian S. , Mason Andrew S. , Gupta Vikas , Dick John E. , Bridge Katherine S. 
Published: July 2024

AbstractHypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival under limited oxygen (hypoxia) and frequently activated within malignancy. Malignant context affects the role of HIFs within oncogenesis; however, the mechanisms regulating HIF context-specificities are not well characterised. Applying the JAK2V617F (JVF) model of myeloproliferative neoplasms (MPNs), in which HIF-1 is active in normoxia (20% O2), we sought to determine whether the modality of HIF-1 activation directs its function. We identify that HIF-1 is stabilised in JVF cells downstream of STAT1/5 signalling and upregulation of PIM1: PIM1 mediates phosphorylation of HIF-1 (Thr498/Ser500) in JVF cells that inhibits proteasomal degradation. PIM1 inhibition eradicates HIF-1 from JVF cells. Applying a single-input dual-omics output chromatin interactome methodology (DOCIA), we define JVF-specific transcription cofactors and genomic redistribution of HIF-1, and a JVF-HIF-1 regulon in primary haematopoietic stem/progenitor cells. In a cohort of 172 JVF-MPN patients, we observe significant association of the JVF-HIF-1 regulon (but strikingly, not canonical HIF-1 genes) with disease severity, progression, and patient survival. Finally, we identify a core set of JVF-HIF-1 targets significantly associated with spontaneous transformation of MPNs to AML. Our findings identify that HIF-1 activation by the JVF-PIM1 axis substantially alters its function, and that this reprogramming drives MPN disease progression, restoring the potential for targeted therapies that delineate HIF-1 activity co-opted by malignancy from essential roles within physiological oxygen homeostasis.Key PointsHIF-1 activation via PIM1 in JAK2V617F-MPNs drives non-canonical transcription complex formation/function.The JAK2V617F-HIF-1 regulon drives MPN disease progression, transformation to AML and worse patient outcomes.
Adult-neurogenesis allows for representational stability and flexibility in early olfactory system
Authors: Chen Zhen , Padmanabhan Krishnan 
Published: July 2024

AbstractIn the early olfactory system, adult-neurogenesis, a process of neuronal replacement results in the continuous reorganization of synaptic connections and network architecture throughout the animal’s life. This poses a critical challenge: How does the olfactory system maintain stable representations of odors and therefore allow for stable sensory perceptions amidst this ongoing circuit instability? Utilizing a detailed spiking network model of early olfactory circuits, we uncovered dual roles for adult-neurogenesis: one that both supports representational stability to faithfully encode odor information and also one that facilitates plasticity to allow for learning and adaptation. In the main olfactory bulb, adult-neurogenesis affects neural codes in individual mitral and tufted cells but preserves odor representations at the neuronal population level. By contrast, in the olfactory piriform cortex, both individual cell responses and overall population dynamics undergo progressive changes due to adult-neurogenesis. This leads to representational drift, a gradual alteration in sensory perception. Both processes are dynamic and depend on experience such that repeated exposure to specific odors reduces the drift due to adult-neurogenesis; thus, when the odor environment is stable over the course of adult-neurogenesis, it is neurogenesis that actually allows the representations to remain stable in piriform cortex; when those olfactory environments change, adult-neurogenesis allows the cortical representations to track environmental change. Whereas perceptual stability and plasticity due to learning are often thought of as two distinct, often contradictory processing in neuronal coding, we find that adult-neurogenesis serves as a shared mechanism for both. In this regard, the quixotic presence of adult-neurogenesis in the mammalian olfactory bulb that has been the focus of considerable debate in chemosensory neuroscience may be the mechanistic underpinning behind an array of complex computations.
Innovative Use of Depth Data to Estimate Energy Intake and Expenditure in Adélie Penguins
Authors: Dupuis Benjamin , Kato Akiko , Hicks Olivia , Wisniewska Danuta M. , Marciau Coline , Angelier Frederic , Ropert-Coudert Yan , Chimienti Marianna 
Published: July 2024

AbstractEnergy governs species’ life histories and pace of living, requiring individuals to make trade-offs. However, measuring energetic parameters in the wild is challenging, often resulting in data collected from heterogeneous sources. This complicates comprehensive analysis and hampers transferability within and across case studies. We present a novel framework, combining information obtained from eco-physiology and bio-logging techniques, to estimate both energy expended and acquired on 48 Adélie penguins (Pygoscelis adeliae) during the chick-rearing stage.We employ the machine learning algorithm random forest (RF) to predict accelerometry-estimated foraging behaviour using depth data (our proxy for energy acquisition). We also build a time-activity model calibrated with doubly labelled water data to estimate energy expenditure.Using depth-derived time spent diving and amount of vertical movement in the sub-surface phase, we accurately predict energy expenditure (R² = 0.70). Movement metrics derived from depth data modelled with the RF algorithm were able to accurately (accuracy = 0.82) detect the same foraging behaviour predicted from accelerometry. The RF more accurately predicted accelerometry-estimated time spent foraging (R² = 0.81) compared to historical proxies like number of undulations (R² = 0.51) or dive bottom duration (R² = 0.31).The proposed framework is accurate, reliable and simple to implement, enabling to couple energy intake and expenditure, which is crucial to further assess individual trade-offs. We provide universal guidelines for predicting these parameters based on widely used bio-logging technology in marine species. Our work allows us to revisit historical data, to study how long-term environmental changes affect animals’ energetics.Summary statementUsing machine learning, we estimated energy expenditure and foraging activity of free-ranging Adélie penguins using depth data recorded with bio-logging devices.
Molecular Insights into AGS3’s Role in Spindle Orientation: A Biochemical Perspective
Authors: Yu Shi , Ji Jie , Liu Zhijun , Wang Wenning 
Published: July 2024

AbstractThe intrinsic regulation of spindle orientation during asymmetric cell division (ACD) depends on the evolutionarily conserved protein complex LGN (Pins)/NuMA (Mud)/Gα·GDP. While the role of LGN and itsDrosophilaorthologue Pins is well-established, the function of AGS3, the paralogue of LGN, in spindle orientation during cell division remains controversial. This study substantiates the contentious nature of AGS3’s function through systematic biochemical characterizations. The results confirm the high conservation of AGS3 in its functional structural domains, similar to LGN, and its comparable ability to bind partners including NuMA, Insc and Gαi3·GDP. However, in contrast to LGN, AGS3 and the microtubule-binding protein NuMA are unable to form stable hetero-hexamers or higher-order oligomeric complexes that are pivotal for effective regulation of spindle orientation. It was found that this notable difference between AGS3 and LGN stems from the N-terminal sequence preceding the conserved TPR motifs, which spans approximately 20 residues. Furthermore, our findings substantiate the disruptive effect of Insc on the oligomeric AGS3/NuMA complex, while showing no impact on the oligomeric LGN/NuMA complex. Consequently, Insc emerges as an additional regulatory factor that distinguishes the functional roles of AGS3 and LGN, leading to the impairment of AGS3’s ability to actively reorient the mitotic spindle. These results elucidate the molecular basis underlying the observed functional disparity in spindle orientation between LGN and AGS3, providing valuable insights into the regulation of cell division at the molecular level.
Long-lasting negative effects of past forestation on grassland pollination networks and their function
Authors: Hirayama Gaku S. , Inoue Taiki , Kenta Tanaka , Ishii Hiroshi S. , Ushimaru Atushi 
Published: July 2024

AbstractGrasslands are facing a rapid decline worldwide. Among the primary threats to these ecosystems are changes in land use, such as land abandonment and forestation, which promote forest vegetation in detriment of grassland plant diversity. To support the conservation and restoration of grasslands, it is key to understand what ecological processes limit the recovery of their biodiversity and functions after perturbations. However, we still know little about the legacy effects of forestation on the ecological mechanisms involved in the recovery of grasslands, especially concerning long-lasting impacts on plant-pollinator interaction networks and plant reproduction.Here, we aim to fill this gap of knowledge by comparing the plant and pollinator diversity, the degree of network generalization, the pollination success and pollen limitation of native plant species in 30 plant-pollinator networks of old-growth and restored grasslands of different ages since recovery (from 2 to 84 years). We hypothesized that past forestation would exert long-lasting legacy negative effects on plant richness and plant-pollinator networks, increasing pollen limitation for native plants, thereby delaying community recovery in restored grasslands.Results showed that restored grasslands exhibited significantly lower plant richness, less specialized (more generalized) interaction networks, lower pollination success and pollen-limited seed reproduction of native plants compared to old-growth grasslands. Meanwhile, the degree of network specialization and pollination success gradually increased with time after grassland restoration initiated. Overall, network generalization, which was caused by low plant richness, reduced pollination and reproduction success in native grassland plants, and degraded pollination networks and functions could recover in restored grasslands with continuous management. These findings imply that plant diversity restoration was slow because of the negative feedbacks associated with low plant richness and consequently, generalized plant-pollinator interaction networks, which diminished native plant reproduction in restored grasslands.Synthesis and applicationsOur findings suggest that the recovery of specialized plant-pollinator networks by enhancing plant diversity is essential for restoring pollination function. For quicker grassland restoration, it may be effective to facilitate the establishment of highly specialized pollination networks by seeding or planting diverse native plants collected from neighbouring areas while avoiding genetic contamination.
Reproductive output of old polygynous males is limited by seminal fluid, not sperm number
Authors: Sanghvi Krish , Shandilya Sucheta , Brown Alana , Todorova Biliana , Jahn Martin , Gascoigne Samuel J.L. , Camilleri Tara-Lyn , Pizzari Tommaso , Sepil Irem 
Published: July 2024

AbstractAdvancing male age can lead to reproductive senescence, which in males is thought to be largely driven by declines in the numbers of sperm transferred by old males. This decline is predicted to be particularly pronounced in polygynous species, where males become sperm limited over a mating sequence. However, males also transfer seminal fluid to females, and little is known about the contribution of seminal fluid to constrain the reproductive output of old, multiply-mating males. UsingDrosophila melanogaster, we investigated whether age-related variation in male reproductive output is driven by differential limitation of sperm or seminal fluid, over a series of experimental matings. Consistent with reproductive senescence, old males produced fewer offspring than young males. However, this pattern was not driven by sperm limitation, with old males having more sperm and transferring similar numbers of sperm to a female, compared to young males. Yet surprisingly, females stored fewer sperm when mated to old than young males. Notably, females mated to old multiply-mating males produced more offspring when supplemented with seminal fluid, suggesting that fertility of old males over successive matings was limited by seminal fluid availability. Generally, our study indicates that germline maintenance might be prioritised over somatic maintenance as hypothesized by the disposable soma theory of ageing, and that seminal fluid senescence is a key contributor of reproductive decline with age. While other factors such as differential sperm viability and female post-mating responses could have also influenced our results, our study highlights the under-appreciated role of seminal fluid in mediating male reproductive senescence in polygynous species.Significance statementA key assumption in ageing research is that old males are less fertile than young males, and that this reduced fertility is partly driven by old males producing fewer sperm. However, senescence in male fertility can be caused via other ejaculate-mediated pathways, which we investigate using fruit flies. Contrary to expectations, we reveal that senescence in male fertility is not because of declines in male sperm reserves, but is instead due to age-related changes in seminal fluid and differences in female sperm storage with male age. These declines in the reproductive output of old, multiply-mating males are alleviated by supplementing females with “extra” seminal fluid. Our study demonstrates that male reproductive senescence is reversible, highlighting the underappreciated role of seminal fluid in modulating senescence in polygynous species. These results have potential for improving animal fertility and our understanding of sexual selection.
iTome Volumetric Serial Sectioning Apparatus for TEM
Authors: Peale David R. , Hess Harald , Lee P. R. , Cardona Albert , Bock Davi D. , Schneider-Mizell Casey , Fetter Richard D. , Lee Wei-Ping , Robinson Camenzind G. , Iyer Nirmala , Managan Claire 
Published: July 2024

ABSTRACTAn automated ultra-microtome capable of sectioning thousands of ultrathin sections onto standard TEM slot grids was developed and used to section: a completeDrosophila melanogasterfirst-instar larva, three sections per grid, into 4,866 34-nm-thick sections with a cutting and pickup success rate of 99.74%; 30 microns of mouse cortex measuring roughly 400 um x 2000 um at 40 nm per slice; and a full adultDrosophilabrain and ventral nerve column into 9,300 sections with a pickup success rate of 99.95%. The apparatus uses optical interferometers to monitor a reference distance between the cutting knife and multiple sample blocks. Cut sections are picked up from the knife-boat water surface while they are still anchored to the cutting knife. Blocks without embedded tissue are used to displace tissue-containing sections away from the knife edge so that the tissue regions end up in the grid slot instead of on the grid rim.
Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung
Authors: Whyte Declan , Voorde Johan Vande , Sumpton David , Dhayade Sandeep , Dornier Emmanuel , Moore Madeleine , Novo David , Peters Jasmine , Wiesheu Robert , Mackey John B.G. , McFarlane Amanda J. , Fercoq Frédéric , Fisher Sophie , Caballero Carolina Dehesa , Gilroy Kathryn , Redmond Keara L. , Mitchell Louise E. , Anderson Eve , Thomson Gemma , Dzierozynski Lindsey N. , Saab Juan J. Apiz , Lewis Caroline A. , Muir Alexander , Halbrook Christopher J. , Strathdee Douglas , Jackstadt Rene , Nixon Colin , Dunne Philip , Steele Colin W. , Carlin Leo M. , Macpherson Iain R. , Roberts Edward W. , Coffelt Seth B. , Blyth Karen , Sansom Owen J. , Norman Jim C. , Clarke Cassie J. 
Published: July 2024

SummaryUnderstanding the mechanisms that facilitate early events in metastatic seeding is key to developing therapeutic approaches to reduce metastasis – the leading cause of cancer-related death. Using whole animal screens in genetically engineered mouse models of cancer we have identified circulating metabolites associated with metastasis. Specifically, we highlight the pyrimidine uracil as a prominent metastasis-associated metabolite. Uracil is generated by neutrophils expressing the enzyme uridine phosphorylase-1 (UPP1), and neutrophil specificUpp1expression is increased in cancer. Altered UPP1 activity influences expression of adhesion molecules on the surface of neutrophils, leading to decreased neutrophil motility in the pre-metastatic lung. Furthermore, we find that UPP1-expressing neutrophils suppress T-cell proliferation, and the UPP1 product uracil can increase fibronectin deposition in the extracellular microenvironment. Consistently, knockout or inhibition of UPP1 in mice with mammary tumours increases the number of T-cells and reduces fibronectin content in the lung and decreases the proportion of mice that develop lung metastasis. These data indicate that UPP1 influences neutrophil behaviour and extracellular matrix deposition in the lung and suggest that pharmacological targeting of this pathway could be an effective strategy to reduce metastasis.