bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centromeres are Hotspots for Chromosomal Inversions and Breeding Traits in Mango
Authors: Wilkinson Melanie J. , McLay Kathleen , Kainer David , Elphinstone Cassandra , Dillon Natalie L. , Webb Matthew , Wijesundara Upendra K. , Ali Asjad , Bally Ian S.E. , Munyengwa Norman , Furtado Agnelo , Henry Robert J. , Hardner Craig M. , Ortiz-Barrientos Daniel 
Published: May 2024

AbstractChromosomal inversions can preserve combinations of favorable alleles by suppressing recombination. Simultaneously, they reduce the effectiveness of purifying selection enabling deleterious alleles to accumulate. This study explores how areas of low recombination, including centromeric regions and chromosomal inversions, contribute to the accumulation of deleterious and favorable loci in 225Mangifera indicagenomes from the Australian Mango Breeding Program. Here, we identify 17 chromosomal inversions that cover 7.7% (29.7Mb) of theM. indicagenome: eight pericentric (inversion includes the centromere) and nine paracentric (inversion is on one arm of the chromosome). Our results show that these large pericentric inversions are accumulating deleterious loci, while the paracentric inversions show deleterious levels above and below the genome wide average. We find that despite their deleterious load, chromosomal inversions contain small effect loci linked to variation in crucial breeding traits, indicating that chromosomal inversions have likely facilitated their selection. The results from this study have important implications for selective breeding of favorable combinations of alleles in regions of low recombination.Significance StatementChromosomal inversions and other low recombination regions of the genome can drive trait evolution. Fewer recombination events can assist in maintaining favorable combinations of alleles, but it can also make disentangling favorable and deleterious alleles difficult. Understanding whether these low recombination regions contain favorable or deleterious loci could drive our decision to increase or decrease the frequency of these regions in target breeding populations. Breeding for large segments of the genome based on presence or absence of an inversion can rapidly drive large trait differences within few generations. Harnessing the impact of large low recombination regions of the genome could have major implications for future genetic improvement in breeding.
Molecular Matchmakers: Phytoplasma Effector SAP54 Targets MADS-Box Factor SVP to Enhance Attraction of Fecund Female Vectors by Modulating Leaf Responses to Male Presence
Authors: Orlovskis Zigmunds , Singh Archana , Kliot Adi , Huang Weijie , Hogenhout Saskia A. 
Published: May 2024

AbstractObligate parasites often trigger significant changes in their hosts to facilitate transmission to new hosts. The molecular mechanisms behind these extended phenotypes - where genetic information of one organism is manifested as traits in another - remain largely unclear. This study explores the role of the virulence protein SAP54, produced by parasitic phytoplasmas, in attracting leafhopper vectors. SAP54 is responsible for the induction of leaf-like flowers in phytoplasma-infected plants. However, we previously demonstrated that the insects were attracted to leaves and the leaf-like flowers were not required. Here we made the surprising discovery that leaf exposure to leafhopper males is required for the attraction phenotype, suggesting a leaf response that distinguishes leafhopper sex in the presence of SAP54. In contrast, this phytoplasma effector alongside leafhopper females discourages further female colonization. We demonstrate that SAP54 effectively suppresses biotic stress response pathways in leaves exposed to the males. Critically, the host plant MADS-box transcription factor SHORT VEGETATIVE PHASE (SVP) emerges as a key element in the female leafhopper preference for plants exposed to males, with SAP54 promoting the degradation of SVP. This preference extends to female colonization of male-exposedsvp nullmutant plants over those not exposed to males. Our research underscores the dual role of the phytoplasma effector SAP54 in host development alteration and vector attraction - integral to the phytoplasma life cycle. Importantly, we clarify how SAP54, by targeting SVP, heightens leaf vulnerability to leafhopper males, thus facilitating female attraction and subsequent plant colonization by the insects. SAP54 essentially acts as a molecular "matchmaker," helping male leafhoppers more easily locate mates by degrading SVP-containing complexes in leaves. This study not only provides insights into the long reach of single parasite genes in extended phenotypes, but also opens avenues for understanding how transcription factors that regulate plant developmental processes intersect with and influence plant-insect interactions.
Channel width modulates the permeability of DNA origami based nuclear pore mimics
Authors: Feng Qingzhou , Saladin Martin , Wu Chunxiang , Cao Eason , Zheng Wei , Zhang Amy , Bhardwaj Pushpanjali , Li Xia , Shen Qi , Kapinos Larisa E. , Mariappan Malaiyalam , Lusk C. Patrick , Xiong Yong , Lim Roderick Y. H. , Lin Chenxiang 
Published: May 2024

AbstractNucleoporins (nups) in the central channel of nuclear pore complexes (NPCs) form a selective barrier that suppresses the diffusion of most macromolecules while enabling rapid transport of nuclear transport receptors (NTRs) with bound cargos. The complex molecular interactions between nups and NTRs have been thought to underlie the gatekeeping function of the NPC. Recent studies have shown considerable variation in NPC diameter but how altering NPC diameter might impact the selective barrier properties remains unclear. Here, we build DNA nanopores with programmable diameters and nup arrangement to mimic NPCs of different diameters. We use hepatitis B virus (HBV) capsids as a model for large-size cargos. We find that Nup62 proteins form a dynamic cross-channel meshwork impermeable to HBV capsids when grafted on the interior of 60-nm wide nanopores but not in 79-nm pores, where Nup62 cluster locally. Furthermore, importin-β1 substantially changes the dynamics of Nup62 assemblies and facilitates the passage of HBV capsids through NPC mimics containing Nup62 and Nup153. Our study shows the transport channel width is critical to the permeability of nup barriers and underscores the role of NTRs in dynamically remodeling nup assemblies and mediating the nuclear entry of viruses.
Obscured Complexity: How External Cycles Simplify the Dynamics of the Endogenous Circadian Oscillator–take the time series of body temperature records as an example
Authors: Lin Feng 
Published: May 2024

AbstractBackgroundUnderstanding circadian rhythms is crucial in various fields of biological research, as they play a fundamental role in the regulation of diverse biological processes, ranging from gene expression to physiological functions.ObjectiveThis study aims to explore the complexity of circadian rhythm signals from a biological system. Without the permission of using experimental data, the mathematical model is utilized to simulate the intricate dynamics of the body temperature’s circadian rhythms and investigate the impact of parameter variation on system behavior.MethodsThe Duffing equation is constructed as the mathematical model for simulating circadian rhythms. A thorough discussion justifies the selection of the Duffing equation and establishes the proper parameter range, ensuring chaotic behavior in the system. Four different values of the driving force parameterγ(0.32, 0.33, 0.34, and 0.35) are chosen to represent specific cases. Fourier analysis is employed to analyze the simulation data, revealing the frequency components present in the circadian rhythm signals. Entropy analysis along the Poincare sections is utilized to measure the system’s behavior and aggregation of points.ResultsThe simulations exhibit distinct characteristics in terms of plain visualization, Fourier analysis, and entropy analysis along the Poincare sections. Under normal work sleep conditions (γ= 0.35), the system demonstrates specific resetting at particular times within a total period. In shift work (γ= 0.34) conditions, some of the resetting behaviour diminishes and the initial phase of the time changes. In longterm constant temperature (γ= 0:33) conditions, resembles that of normal work sleep conditions, with a noticeable reset at the beginning of the period. When all external driving forces are eliminated (γ= 0:32), the system undergoes multiple resets within a given period. In such circumstances, the biological clock experiences more frequent resets to adapt to the independent operations of each subsystem. Without relying on external environmental cues for regulation, the biological clock relies on frequent resetting to maintain the stability and coordination of the entire system.ConclusionThe simulations reveals variations in resetting behavior and the importance of frequent resets in the absence of external cues. The complexity arising from chaos allows the biological system to adapt and adjust to the intricacies of the external environment. The endogenous clock within the system, despite its inherent complexity, can dynamically optimize its entrainment with external cycles. However, the full complexity of the endogenous clock may be concealed within the system and not readily observable. These findings contribute to a better understanding of the complex dynamics of circadian rhythms. Future research should aim to validate these results through comparisons with experimental data.
Inequalities in access to and outcomes of cardiac surgery in England: retrospective analysis of Hospital Episode Statistics (2010-2019)
Authors: Lai Florence Y , Gibbison Ben , O’Cathain Alicia , Akowuah Enoch , Cleland John , Angelini Gianni D , King Christina , Murphy Gavin J , Pufulete Maria 
Published: May 2024

ObjectivesTo characterise the variation in access to and outcomes of cardiac surgery for people in England.MethodsWe included people >18 years of age with a hospital admission for ischaemic heart disease (IHD) and heart valve disease (HVD) between 2010 and 2019. Within these populations, we identified patients who had coronary artery bypass graft (CABG) and/or valve surgery, respectively. We fitted logistic regression models to examine the effects of age, sex, ethnicity and socio-economic deprivation on having access to surgery and in-hospital mortality, 1-year mortality and hospital readmission.ResultsWe included 292,140 people, of whom 28% were women, 11% were from an ethnic minority and 17% were from the most deprived areas. Across all types of surgery, 1 in 5 patients are readmitted to hospital within 1 year, rising to almost 1 in 4 for valve surgery patients. Women, Black people and people living in the most deprived areas were less likely to have access to surgery (CABG: 59%, 32%, 35% less likely; valve: 31%, 33%, 39% less likely, respectively) and more likely to die within 1 year of surgery (CABG: 24%, 85%, 18% more likely, respectively; valve: 19% (women) and 10% (people from most deprived areas) more likely).ConclusionFemale sex, Black ethnicity, and economic deprivation are independently associated with limited access to cardiac surgery and higher post-surgery mortality. Actions are required to address these inequalities.WHAT IS ALREADY KNOWN ON THIS TOPICThere has been a marked improvement in short term (in hospital) outcomes of people having cardiac surgery. It is not clear if this translates to improvement in mid- and long-term outcomes and how these differ by demographic and socio-economic factors.WHAT THIS STUDY ADDSAcross all types of cardiac surgery, 1 in 5 patients are readmitted to hospital within 1 year of surgery, rising to almost 1 in 4 for valve surgery patients.While in hospital mortality has decreased markedly since 2010 (by 20%), 1 year mortality and hospital readmission remained largely unchanged.Women, people of Black ethnicity and people from the most socially deprived areas were less likely to be offered cardiac surgery and more likely to die and be readmitted to hospital in the year after surgery.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYTargeted interventions are required across the cardiovascular medicine pathway to improve mid- and long-term outcome in patients having cardiac surgery, addressing inequalities.
11β-HSD1 inhibitor efficacy in type 2 diabetes is cortisol-dependent
Authors: Wilton-Waddell Atinuke , Farraj Layal Abi , Vasconcelos Elton JR , Byrne Emily , Taylor Angela E , Freeman Adrian , Etal Damla , Stewart Paul M , Arlt Wiebke , Ajjan Ramzi , Tiganescu Ana 
Published: May 2024

ABSTRACTCortisol excess drives multiple adverse effects including hypertension, dyslipidemia, and delayed wound healing. Activation of cortisol by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has shown promise as a therapeutic target for these comorbidities but clinical progress has been hampered by variable 11β-HSD1 inhibitor efficacy. Here, transcriptomic profiling of 11β-HSD1 target genes in primary skin fibroblasts as well as skin biopsies from type 2 diabetes individuals treated with the selective 11β-HSD1 inhibitor AZD4017 provide detailed mechanistic insights highlighting new areas of therapeutic potential. We report correlations between changes in 11β-HSD1 target gene expression, blood pressure, lipids, and wound healing with 1) cortisol levels (serum cortisol / dehydroepiandrosterone sulfate) and 2) peripheral 11β-HSD1 activity (serum cortisol / cortisone). Finally, we demonstrate that baseline cortisol levels and changes in placebo group cortisol levels are key determinants of 11β-HSD1 inhibitor efficacy. In conclusion, our findings pave the way for more effective targeting of 11β-HSD1 inhibitor treatment, improving the accuracy of future clinical studies. Larger trials of longer duration are now warranted to fully explore the therapeutic potential of 11β-HSD1 inhibitors across a range of cardiometabolic and age-associated indications.
Laboratory Readiness and genomic surveillance of Covid-19 in the Capital of Brazil
Authors: Cavalcante Fabrício Vieira , Martin Christina Pacheco Santos , Frio Gustavo Saraiva , Stabeli Rodrigo Guerino , Santos Leonor Maria Pacheco 
Published: May 2024

AbstractObjectiveAnalyze the diagnostic readiness to Covid-19 and the genomic surveillance of SARS-CoV-2 in Brasília, the capital of Brazil.MethodRetrospective, cross-sectional study, with data from: cases/deaths - Ministry of Health; RT-PCR analyzes Brasília Central Public Health Laboratory (LACEN); genomics - Global Initiative on Sharing All Influenza Data (GISAID).ResultsIn March 2021, with the Gamma variant being predominant, RT-PCR dosages by LACEN reached their peak, followed by a reduction, possibly due to the start of vaccination. New peaks were observed in September 2021 and January 2022. The average time for releasing RT-PCR results was reduced from eight days (July 2020), to around eight hours in 2023. The participation of private laboratories was evident in sequencing the SARS-CoV-2 variants of concern in Brasília (n=1,897). LACEN received 571 samples, sequencing 50%. A decrease in the incidence of cases and deaths due to Covid-19 was noted in the years 2022 to 2023, following the national trend.ConclusionLACEN maintained RT-PCR dosages satisfactorily throughout the period. Regarding the genomic surveillance of SARS-CoV-2, the vast majority of samples were sequenced by private laboratories and the sequencing predicted by LACEN was not covered in its entirety.
Highly reduced complementary genomes of dual bacterial symbionts in the mulberry psyllidAnomoneura mori
Authors: Yasuda Yuka , Inoue Hiromitsu , Hirose Yuu , Nakabachi Atsushi 
Published: May 2024

AbstractThe genomes of obligately host-restricted bacteria suffer from accumulating mildly deleterious mutations, resulting in a drastic size reduction. Psyllids (Hemiptera) are phloem sap-sucking insects with a specialized organ called the bacteriome, which typically harbors two vertically transmitted bacterial symbionts: the primary symbiont “CandidatusCarsonella ruddii” (Gammaproteobacteria) and a secondary symbiont phylogenetically diverse among psyllid lineages. Genomes of severalCarsonellalineages were revealed to be drastically reduced (158-174 kb), AT-rich (14.0–17.9% GC), and structurally conserved with similar gene inventories devoted for synthesizing essential amino acids scarce in the phloem sap. However, genomic information for secondary symbionts was limited. Hence, this study analyzed genomes of the bacteriome-associated dual symbionts, Secondary_AM (Gammaproteobacteria) andCarsonella_AM, in the mulberry psyllidAnomoneura mori(Psyllidae). This revealed that the Secondary_AM genome is as small and AT-rich (229,822 bp, 17.3% GC) as those ofCarsonella, includingCarsonella_AM (169,120 bp, 16.2% GC), implying that Secondary_AM is an evolutionarily ancient obligate mutualist likeCarsonella. Phylogenomic analyses demonstrated that Secondary_AM is sister to “CandidatusPsyllophila symbiotica” ofCacopsyllaspp. (Psyllidae), whose genomes (221–237 kb, 17.3–18.6% GC) were recently reported. The Secondary_AM andPsyllophilagenomes showed highly conserved synteny, sharing all genes for complementing the incomplete tryptophan biosynthetic pathway ofCarsonellaand genes for synthesizing B vitamins. However, sulfur assimilation and carotenoid synthesizing genes were retained only in Secondary_AM andPsyllophila, respectively, indicating ongoing gene silencing. Average nucleotide identity, gene ortholog similarity, genome-wide synteny, and substitution rates suggested that the Secondary_AM/Psyllophilagenomes are more labile than theCarsonellagenomes.
Selective regulation of kinesin-5 function by β-tubulin carboxy-terminal tails
Authors: Thomas Ezekiel C. , Moore Jeffrey K. 
Published: May 2024

AbstractThe tubulin code hypothesis predicts that carboxy-terminal tails of tubulins create programs for selective regulation of microtubule-binding proteins, including kinesin motors. However, the molecular mechanisms that determine selective regulation and their relevance in cells are poorly understood. In this work, we report selective regulation of budding yeast kinesin-5 motors, Cin8 and Kip1, by the β-tubulin tail. Cin8, but not Kip1, requires the β-tubulin tail for its recruitment to the mitotic spindle. This creates a balance of both kinesin-5 motors in the spindle, and efficient mitotic progression. We identify a negatively charged patch of acidic amino acids in the β-tubulin tail that mediates the interaction with Cin8in vivo. Usingin vitroreconstitution with genetically modified yeast tubulin, we demonstrate that the charged patch in the β-tubulin tail increases Cin8 plus-end directed velocity and processivity. Finally, we determine that the positively charged amino-terminal extension from the Cin8 motor domain coordinates interactions with the β-tubulin tail. This work provides the first demonstration of a molecular mechanism underlying selective regulation of closely related kinesin motors by tubulin tails, and how this regulation promotes proper function of the mitotic spindle.
Structural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70
Authors: Morizono Marc A. , McGuire Kelly L. , Birouty Natalie I. , Herzik Mark A. 
Published: May 2024

AbstractMaintenance of protein homeostasis is necessary for cell viability and depends on a complex network of chaperones and co-chaperones, including the heat-shock protein 70 (Hsp70) system. In human mitochondria, mitochondrial Hsp70 (mortalin) and the nucleotide exchange factor (GrpEL1) work synergistically to stabilize proteins, assemble protein complexes, and facilitate protein import. However, our understanding of the molecular mechanisms guiding these processes is hampered by limited structural information. To elucidate these mechanistic details, we used cryoEM to determine the first structures of full-length human mortalin-GrpEL1 complexes in previously unobserved states. Our structures and molecular dynamics simulations allow us to delineate specific roles for mortalin-GrpEL1 interfaces and to identify steps in GrpEL1-mediated nucleotide and substrate release by mortalin. Subsequent analyses reveal conserved mechanisms across bacteria and mammals and facilitate a complete understanding of sequential nucleotide and substrate release for the Hsp70 chaperone system.
SlSAURs, targeted by SlSTOP1, inhibit SlPP2C.Ds to modulate H+-ATPase and tomato root elongation under aluminum stress
Authors: Dong Danhui , Deng Qilin , Zhang Jialong , Jia Congyang , Zhang Lei , Li Hongxin , Zhang Na , Guo Yang-Dong 
Published: May 2024

AbstractAluminum (Al) stress, a prevalent constraint in acid soils, is known to inhibit plant growth by inhibiting root elongation through restricted cell expansion. The molecular mechanisms of Al-induced root inhibition, however, are not fully understood. This study aimed to elucidate the role of SlSAUR (Small auxin up-regulated RNA) proteins, which were downstream of the key Al stress-responsive transcription factor SlSTOP1 and its enhancer SlSZP1, in modulating root elongation under Al stress in tomato (Solanum lycopersicum). Our findings demonstrated that tomato lines withSlSAURsknockout exhibited shorter root lengths when subjected to Al stress. Further investigation into the underlying mechanisms revealed that SlSAURs interact with D-clade type 2C protein phosphatases, specifically SlPP2C.Ds. This interaction was pivotal as it suppresses the phosphatase activity, leading to the derepression of SlPP2C.D’s inhibitory effect on H+-ATPase. Consequently, this promoted cell expansion and root elongation under Al stress conditions. Our research significantly contributes to the current understanding of the molecular mechanisms by which Al ions modulate root elongation. The discovery of the SlSAUR-SlPP2C.D interaction and its impact on H+-ATPase activity provides a novel perspective on the adaptive strategies employed by plants to cope with Al toxicity. This knowledge may pave the way for the development of tomato cultivars with enhanced Al stress tolerance, thereby improving crop productivity in acid soils.
Working memory recovery in adolescents with concussion: Longitudinal fMRI study
Authors: Manelis A. , Lima Santos J.P. , Suss S.J. , Perry C.A. , Hickey R.W. , Collins M.W. , Kontos A.P. , Versace A. 
Published: May 2024

ABSTRACTBackgroundUnderstanding behavioral and neural underpinnings of post-concussion recovery of working memory function is critically important for improving clinical outcomes and adequately planning return-to-activity decisions. Previous studies provided inconsistent results due to small sample sizes and the use of a mixed population of participants who were at different post-injury time points.MethodsTo better understand behavioral and neural correlates of working memory recover during the first 6 months post-concussion, we used functional magnetic resonance imaging (fMRI) to scan 45 concussed adolescents [CONC] at baseline (<10 days post-concussion) and again at 6 months post-concussion. Healthy control [HC] adolescents without a history of concussion were scanned once. During the scans, participants performed 1-back (easy) and 2-back (difficult) working memory tasks with the letters as the stimuli and angry, happy, neutral, and sad faces as distractors.ResultsBy the 6-month follow-up, all affected adolescents were asymptomatic and cleared to return-to-activity. Working memory function recovery was reflected by faster and more accurate performance at 6 months vs. baseline (p-values<0.05). It was also characterized by significant difficulty-related activation increases in the left inferior frontal gyrus (LIFG) and the left orbitofrontal cortex (LOFC) at 6 months vs. baseline.ConclusionPost-concussion recovery is associated with significant performance improvements in speed and accuracy, as well as normalization of brain responses in the LIFG and LOFC during the n-back task. The observed patterns of LOFC activation might reflect compensatory strategies to distribute neural processing and reduce neural fatigue post-concussion.