bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interfered Chromosome Pairing Promotes Meiosis Instability of Autotetraploid Arabidopsis by High Temperatures
Authors: Fu Huiqi , Zhao Jiayi , Ren Ziming , Yang Ke , Wang Chong , Zhang Xiaohong , Elesawi Ibrahim Eid , Zhang Xianhua , Xia Jing , Chen Chunli , Lu Ping , Chen Yongxing , Liu Hong , Yu Guanghui , Liu Bing 
Published: September 2021

AbstractAlterations of environmental temperature affect multiple meiosis processes in flowering plants. Polyploid plants derived from whole genome duplication (WGD) have enhanced genetic plasticity and tolerance to environmental stress, but meanwhile face a challenge for organization and segregation of doubled chromosome sets. In this study, we investigated the impact of increased environmental temperature on male meiosis in autotetraploid Arabidopsis thaliana. Under low to mildly-increased temperatures (5-28°C), irregular chromosome segregation universally takes place in synthesized autotetraploid Columbia-0 (Col-0). Similar meiosis lesions occur in autotetraploid rice (Oryza sativa L.) and allotetraploid canola (Brassica napus cv. Westar), but not in evolutionary-derived hexaploid wheat (Triticum aestivum). As temperature increases to extremely high, chromosome separation and tetrad formation are severely disordered due to univalent formation caused by suppressed crossing-over. We found a strong correlation between tetravalent formation and successful chromosome pairing, both of which are negatively correlated with temperature elevation, suggesting that increased temperature interferes with crossing-over prominently by impacting homolog pairing. Besides, we showed that loading irregularities of axis proteins ASY1 and ASY4 co-localize on the chromosomes of syn1 mutant, and the heat-stressed diploid and autotetraploid Col-0, revealing that heat stress affects lateral region of synaptonemal complex (SC) by impacting stability of axis. Moreover, we showed that chromosome axis and SC in autotetraploid Col-0 are more sensitive to increased temperature than that of diploid Arabidopsis. Taken together, our study provide evidence suggesting that WGD without evolutionary and/or natural adaption negatively affects stability and thermal tolerance of meiotic recombination in Arabidopsis thaliana.
Structural basis of Plasmodium vivax inhibition by antibodies binding to the circumsporozoite protein repeats
Authors: Kucharska Iga , Hossain Lamia , Ivanochko Danton , Yang Qiren , Rubinstein John L , Pomès Régis , Julien Jean-Philippe 
Published: September 2021

AbstractMalaria is a global health burden, with Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) responsible for the majority of infections worldwide. Circumsporozoite protein (CSP) is the most abundant protein on the surface of Plasmodium sporozoites, and antibodies targeting the central repeat region of CSP can prevent parasite infection. Although much has been uncovered about the molecular basis of antibody recognition of the PfCSP repeats, data remains scarce for PvCSP. Here, we performed molecular dynamics simulations for peptides comprising the PvCSP repeats from strains VK210 and VK247 to reveal how the PvCSP central repeats are highly disordered, with minor propensities to adopt turn conformations. Next, we solved eight crystal structures to unveil the interactions of two inhibitory monoclonal antibodies (mAbs), 2F2 and 2E10.E9, with PvCSP repeats. Both antibodies can accommodate subtle sequence variances in the repeat motifs and recognize largely coiled peptide conformations that also contain isolated turns. Our structural studies uncover various degrees of Fab-Fab homotypic interactions upon recognition of the PvCSP central repeats by these two inhibitory mAbs, similar to potent mAbs against PfCSP. These findings augment our understanding of host-Plasmodium interactions, and contribute molecular details of Pv inhibition by mAbs to unlock structure-based engineering of PvCSP-based vaccines.
Vascular risk is not associated with PET measures of Alzheimer’s disease neuropathology among cognitively normal older adults
Authors: Bilgel Murat , Bannerjee Alisa , Shafer Andrea , An Yang , Resnick Susan M. 
Published: September 2021

AbstractCardiovascular disease (CVD) is associated with a higher risk of developing dementia. Studies have found that vascular risk factors are associated with greater amyloid-β (Aβ) and tau burden, which are hallmark neuropathologies of Alzheimer’s disease (AD). Evidence for these associations during the preclinical stages of AD, when Aβ and tau pathologies first become detectable, is mixed. Quantifying the effect of vascular risk among cognitively normal individuals can help focus the efforts to develop therapeutic approaches aimed at modifying the course of preclinical AD.Using Bayesian analysis, we examined the relationship of Aβ and tau pathology with concurrent vascular risk among 87 cognitively normal individuals (median age 77, interquartile range 70– 83) in the Baltimore Longitudinal Study of Aging. We quantified vascular risk as the probability of developing CVD within 10 years using published equations from the Framingham Heart Study. Aβ and tau pathologies were measured using positron emission tomography.As expected, Aβ positive participants had greater tau in the entorhinal cortex (EC) and inferior temporal gyrus (ITG) (difference in means = 0.09, p < 0.05 for each region), and 10-year CVD risk was positively correlated with white matter lesion burden (r = 0.24, p = 0.03). However, we did not find any associations between CVD risk and Aβ or tau. The data provided over two- and four-fold evidence towards the lack of a correlation between CVD risk and tau in the EC (Bayes factor BF = 2.4) and ITG (BF = 4.0), respectively. We found over three-fold evidence towards the lack of a difference in mean CVD risk by Aβ group (BF = 3.4). These null findings were replicated using a data-driven vascular risk score in the BLSA based on a principal component analysis of eight indicators of vascular health.Our data provide moderate evidence towards the lack of an association between vascular risk and concurrent AD neuropathology among cognitively normal older adults. This finding suggests that vascular risk and AD neuropathology may constitute independent pathways in the development of cognitive impairment and dementia.HighlightsVascular risk is associated with white matter lesion load, but not amyloid-β or tauModerate evidence for lack of association between vascular risk & early AD pathologyVascular risk and Alzheimer’s neuropathology may constitute independent pathways
Engineering genetically-encoded synthetic biomarkers for breath-based cancer detection
Authors: Vermesh Ophir , D’Souza Aloma L. , Alam Israt S. , Wardak Mirwais , McLaughlin Theresa , El Rami Fadi , Sathirachinda Ataya , Bell John C. , James Michelle L. , Hori Sharon S. , Gross Eric R. , Gambhir Sanjiv Sam 
Published: September 2021

AbstractBreath analysis holds great promise for rapid, noninvasive early cancer detection; however, clinical implementation is impeded by limited signal from nascent tumors and high background expression by non-malignant tissues. To address this issue, we developed a novel breath-based reporter system for early cancer detection using D-limonene, a volatile organic compound (VOC) from citrus fruit that is not produced in humans, in order to minimize background signal and maximize sensitivity and specificity for cancer detection. We metabolically engineered HeLa human cervical cancer cells to express limonene at levels detectable by mass spectrometry by introducing a single plant gene encoding limonene synthase. To improve limonene production and detection sensitivity twofold, we genetically co-expressed a modified form of a key enzyme in the cholesterol biosynthesis pathway. In a HeLa xenograft tumor mouse model, limonene is a sensitive and specific volatile reporter of tumor presence and growth, permitting detection of tumors as small as 5 mm. Moreover, tumor detection in mice improves proportionally with breath sampling time. By continuously collecting VOCs for 10 hours, we improve sensitivity for cancer detection 100-fold over static headspace sampling methods. Whole-body physiologically-based pharmacokinetic (PBPK) modeling and simulation of tumor-derived limonene predicts detection of tumors as small as 7 mm in humans, equivalent to the detection limit of clinical imaging modalities, such as PET, yet far more economical.Significance StatementWe developed a breath-based reporter system using the plant terpene, D-limonene – a volatile secondary metabolite that gives citrus fruit its characteristic scent but is not produced in human tissues – as a biomarker for early cancer detection. Results from this study could pave the way for in vivo gene delivery and tumor-specific expression of exogenous volatile cancer reporters with broad applicability to the early diagnosis of a wide variety of cancers.
Functional connectivity gradients as a common neural architecture for predictive processing in the human brain
Authors: Katsumi Yuta , Kamona Nada , Zhang Jiahe , Bunce Jamie G. , Hutchinson J. Benjamin , Yarossi Mathew , Tunik Eugene , Quigley Karen S. , Dickerson Bradford C. , Barrett Lisa Feldman 
Published: September 2021

AbstractPredictive processing is emerging as a common computational hypothesis to account for diverse psychological functions subserved by a brain, providing a systems-level framework for characterizing structure-function relationships of its distinct substructures. Here, we contribute to this framework by examining gradients of functional connectivity as a low dimensional spatial representation of functional variation in the brain and demonstrating their computational implications for predictive processing. Specifically, we investigated functional connectivity gradients in the cerebral cortex, the cerebellum, and the hippocampus using resting-state functional MRI data collected from large samples of healthy young adults. We then evaluated the degree to which these structures share common principles of functional organization by assessing the correspondence of their gradients. We show that the organizing principles of these structures primarily follow two functional gradients consistent with the existing hierarchical accounts of predictive processing: A model-error gradient that describes the flow of prediction and prediction error signals, and a model-precision gradient that differentiates regions involved in the representation and attentional modulation of such signals in the cerebral cortex. Using these gradients, we also demonstrated triangulation of functional connectivity involving distinct subregions of the three structures, which allows characterization of distinct ways in which these structures functionally interact with each other, possibly subserving unique and complementary aspects of predictive processing. These findings support the viability of computational hypotheses about the functional relationships between the cerebral cortex, the cerebellum, and the hippocampus that may be instrumental for understanding the brain’s dynamics within its large-scale predictive architecture.
Artificial introns for effective expression of transgenes in mammalian cells
Authors: Naberezhnov D.S. , Lesovaya E.A. , Kirsanov K.I. , Yakubovskaya M.G. 
Published: September 2021

AbstractIntrons are widely used in the assembly of genetic constructions expressing transgenic proteins in eukaryotic cells for the enhancement of this expression. However, the choice of introns that can be applied for such purposes is limited by the excessively large size of the majority of natural introns (several thousand nucleotides) and therefore they cannot be cloned in a genetic construction. With the help of site-directed mutagenesis we have generated a library of short (99 nucleotides long) introns. The efficiency of these introns in the enhancement of gene expression was analyzed. As a result, a set of 12 introns was selected. The generated intros can be used for genetic constructions with high expression level of recombinant proteins.
Domestication Reshaped the Genetic Basis of Inbreeding Depression in a Maize Landrace Compared to its Wild Relative, Teosinte
Authors: Samayoa L.F. , Olukolu B.A. , Yang C.J. , Chen Q. , Stetter Markus G. , York Alessandra M. , Sanchez-Gonzalez Jose de Jesus , Glaubitz Jeffrey C. , Bradbury Peter J. , Romay Maria Cinta , Sun Qi , Yang Jinliang , Ross-Ibarra Jeffrey , Buckler Edward S. , Doebley J.F. , Holland J.B. 
Published: September 2021

AbstractInbreeding depression is the reduction in fitness and vigor resulting from mating of close relatives observed in many plant and animal species. The extent to which the genetic load of mutations contributing to inbreeding depression is due to rare large-effect variation versus potentially more common variants with very small individual effects is unknown and may be affected by population history. We compared the effects of outcrossing and self-fertilization on 18 traits in a landrace population of maize, which underwent a population bottleneck during domestication, and a neighboring population of its wild relative teosinte. Inbreeding depression was greater in maize than teosinte for 15 of 18 traits, congruent with the greater segregating genetic load predicted from sequence data in the maize population. For many traits - and more commonly in maize - genetic variation among selffertilized families was less than expected based on additive and dominance variance estimated in outcrossed families, suggesting that a negative covariance between additive and homozygous dominance effects limits the variation available to selection under partial inbreeding. We identified quantitative trait loci (QTL) representing large-effect rare variants carried by only a single parent, which were more important in teosinte than maize. Teosinte also carried more putative juvenile-acting lethal variants identified by segregation distortion. These results suggest a mixture of mostly polygenic, smalleffect recessive variation underlying inbreeding depression, with an additional contribution from rare larger-effect variants that was more important in teosinte but depleted in maize following to the domestication bottleneck. Purging associated with the maize domestication bottleneck may have selected against large effect variants, but polygenic load is harder to purge and segregating mutational burden increased in maize compared to teosinte.
Update on the mosquito fauna (Diptera: Culicidae) distribution in Cabo Verde: occurrence of the species complexes Anopheles gambiae and Culex pipiens (pipiens, quinquefasciatus and their hybrids)
Authors: Da Veiga Leal Silvânia , Fernandes Varela Isaias Baptista , Sousa Monteiro Davidson Daniel , Ramos de Sousa Celivianne Marisia , Mendonça Maria da Luz Lima , De Pina Adilson José , Lopes Gonçalves Aderitow Augusto , Osório Hugo Costa 
Published: September 2021

AbstractIn this study, we aimed to update the mosquito species composition and distribution based on a national entomological survey in all municipalities of Cabo Verde. This includes the sibling species of the Culex pipiens complex, namely Cx. pipiens, Cx. quinquefasciatus and their hybrids, in locations where information is not available. The entomological survey took place from October 2017 to September 2018, in all municipalities of Cabo Verde. Mosquito larvae and pupae were collected in breeding sites and samples were sent to the Laboratory of Medical Entomology of the National Institute of Public Health for the morphological identification of the species. The mosquitoes morphologically identified in Anopheles gambiae and Culex pipiens complexes of species were further molecular analysed to species confirmation. A total of 814 breeding sites were surveyed and 10 mosquito species of five genera were identified. The greatest number of mosquito species was reported in the island of Santiago. The most widespread species in the country were Aedes aegypti and Culex quinquefasciatus. Anopheles arabiensis was the only species identified in the Gambiae complex of species. The results of this study will assist decision makers in important health policies to control mosquitoes and vector-borne diseases towards a strategic approach by timely detection of changes in species diversity.
Genome-wide association analysis of cotton salt stress response-related sites
Authors: Zheng Juyun , Zhang Zeliang , Gong Zhaolong , Liang Yajun , Sang Zhiwei , Xu YanChao , Li Xueyuan , Wang Jungduo 
Published: September 2021

AbstractSoil salinization is the main abiotic stress factor affecting agricultural production worldwide, and salt stress has a significant impact on plant growth and development. Cotton is one of the most salt-tolerant crops. Its salt tolerance varies greatly depending on the variety, growth stage, organs, and soil salt types. Therefore, the selection and utilization of excellent salt-tolerant germplasm resources and the excavation of excellent salt-tolerant salt and salt resistance genes play important roles in improving cotton production in saline-alkali soils. In this study, we analysed the population structure and genetic diversity of 144 elite Gossypium hirsutum cultivar accessions collected from around the world, and especially from China. Illumina Cotton SNP 70K was used to obtain genome-wide single-nucleotide polymorphism (SNP) data for 149 experimental materials, and 18,432 highly consistent SNP loci were obtained by filtering. PCA (principal component analysis) indicated that 149 upland cotton materials could be divided into 2 subgroups, including subgroup 1 with 78 materials and subgroup 2 with 71 materials. Using the obtained SNP and other marker genotype test results, under salt stress, the salt tolerance traits 3d_Germination_potential, 3d_Bud_length_drop_rate, 7d_Germination_rate, 7d_Bud_length_drop_rate, 7d_Germination_weight, 3d_Bud_length, 7d_Bud_length, relative_germination_potential, Relative_germination_rate, 7d_Bud_weight_drop_rate, Salt tolerance index 3d_Germination_potential_index, 3d_Bud_length_index, 7d_Bud_length_index, 7d_Bud_weight_index, and 7d_Germination_rate_index were evaluated by genome association analysis. A total of 27 SNP markers closely related to salt tolerance traits and 15 SNP markers closely related to salt tolerance index were detected. At the SNP locus associated with the traits of the bud length decline rate at 7 days, alleles Gh_A01G0034 and Gh_D01G0028 related to plant salt tolerance were detected, and they are related to intracellular transport, membrane microtubule formation and actin network. This study provides a theoretical basis for the selection and breeding of salt-tolerant upland cotton varieties.
MAPK cascades mediating Trichoderma brevicrassum strain TC967 against phytopathogen Rhizoctonia solani
Authors: Zhang Yi , Zhuang Wen-Ying 
Published: September 2021

AbstractTrichoderma brevicrassum strain TC967 is a novel biological control agent (BCA) against the plant pathogen Rhizoctonia solani and promotes plant growth. MAPK (mitogen-activated protein kinase) cascades were involved in biocontrol by Trichoderma, but functions of each MAPK in regulating biocontrol have not been characterized in one Trichoderma. In this study, we assembled and annotated the genome of strain TC967, and identified its three MAPK gene sequences. Functions of Fus3-, Slt2- and Hog1-MAPK in strain TC967 were dissected. The three MAPKs were all involved in hyphal growth. The Hog1-MAPK was essential for conidiation and tolerance to hyperosmotic stress. The Fus3- and Slt2-MAPK both mediated cell-wall integrity (CWI) and activities of chitinase and protease. The Fus3- and Hog1-MAPK mediated response to oxidative stress. Our biocontrol assays demonstrated that the Fus3- and Slt2-MAPK mutants were considerably more effective in disease control than the wild-type strain. RNA-seq analysis revealed that MAPK collectively played a major role in regulating biocontrol-related gene expressions, including of the genes in charge of secondary metabolism, fungal cell wall-degrading enzymes (FCWDEs) and small secreted cysteine-rich proteins (SSCPs).Author summarySoil-born fungal pathogens pose an emerging threat to crop production. Trichoderma brevicrassum strain TC967 has the ability to control the notorious phytopathogen Rhizoctonia solani and promote plant growth. In this study, we explored the functions of three-types of MAPK in mediating biocontrol process, and uncovered that Fus3-, Slt2- and Hog1-MAPK are involved in hyphal growth, conidiation, tolerance to hyperosmotic stress, cell-wall integrity, activities of chitinase and protease, and response to oxidative stress. Biocontrol ability of strain TC967 was accelerated after deletion of the Fus3- and Slt2-MAPK genes. MAPK collectively played a major role in regulating biocontrol-related gene expressions as revealed by RNA-seq analysis. To our knowledge, this is the first report of the functions of MAPKs in regulating biocontrol in one Trichoderma. Our results provide a reference for improvement of biocontrol ability of Trichoderma strains from the view of MAPK cascades.
Sites of active gene regulation in the prenatal frontal cortex and their role in neuropsychiatric disorders
Authors: Kouakou Manuela R. , Cameron Darren , Hannon Eilis , Dempster Emma L. , Mill Jonathan , Hill Matthew J. , Bray Nicholas J. 
Published: September 2021

AbstractCommon genetic variation appears to largely influence risk for neuropsychiatric disorders through effects on gene regulation. It is therefore possible to shed light on the biology of these conditions by testing for enrichment of associated genetic variation within regulatory genomic regions operating in specific tissues or cell types. Here, we have used ATAC-Seq to map open chromatin (an index of active regulatory genomic regions) in bulk tissue, NeuN+ and NeuN− nuclei from the prenatal human frontal cortex, and tested enrichment of SNP heritability for 5 neuropsychiatric disorders (autism spectrum disorder, ADHD, bipolar disorder, major depressive disorder and schizophrenia) within these regions. We observed significant enrichment of SNP heritability for ADHD, major depressive disorder and schizophrenia within open chromatin regions mapped in bulk fetal frontal cortex, and for all 5 tested neuropsychiatric conditions when we restricted these sites to those overlapping histone modifications indicative of enhancers (H3K4me1) or promoters (H3K4me3) in fetal brain. SNP heritability for neuropsychiatric disorders was significantly enriched in open chromatin regions identified in fetal frontal cortex NeuN- as well as NeuN+ nuclei overlapping fetal brain H3K4me1 or H3K4me3 sites. We additionally demonstrate the utility of our mapped open chromatin regions for prioritizing potentially functional SNPs at genome-wide significant risk loci for neuropsychiatric disorders. Our data provide evidence for an early neurodevelopmental component to a range of neuropsychiatric conditions and highlight an important role for regulatory genomic regions active within both NeuN+ and NeuN− cells of the prenatal brain.