Cardiometabolic Pregnancy Complications in Association With Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO.

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (ß = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (ß = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

Repeat variants for the SbMATE transporter protect sorghum roots from aluminum toxicity by transcriptional interplay in cis and trans.

Acidic soils, where aluminum (Al) toxicity is a major agricultural constraint, are globally widespread and are prevalent in developing countries. In sorghum, the root citrate transporter SbMATE confers Al tolerance by protecting root apices from toxic Al3+, but can exhibit reduced expression when introgressed into different lines. We show that allele-specific SbMATE transactivation occurs and is caused by factors located away from SbMATE Using expression-QTL mapping and expression genome-wide association mapping, we establish that SbMATE transcription is controlled in a bipartite fashion, primarily in cis but also in trans Multiallelic promoter transactivation and ChIP analyses demonstrated that intermolecular effects on SbMATE expression arise from a WRKY and a zinc finger-DHHC transcription factor (TF) that bind to and trans-activate the SbMATE promoter. A haplotype analysis in sorghum RILs indicates that the TFs influence SbMATE expression and Al tolerance. Variation in SbMATE expression likely results from changes in tandemly repeated cis sequences flanking a transposable element (a miniature inverted repeat transposable element) insertion in the SbMATE promoter, which are recognized by the Al3+-responsive TFs. According to our model, repeat expansion in Al-tolerant genotypes increases TF recruitment and, hence, SbMATE expression, which is, in turn, lower in Al-sensitive genetic backgrounds as a result of lower TF expression and fewer binding sites. We thus show that even dominant cis regulation of an agronomically important gene can be subjected to precise intermolecular fine-tuning. These concerted cis/trans interactions, which allow the plant to sense and respond to environmental cues, such as Al3+ toxicity, can now be used to increase yields and food security on acidic soils.

A Begomovirus Nuclear Shuttle Protein-Interacting Immune Hub: Hijacking Host Transport Activities and Suppressing Incompatible Functions.

Begomoviruses (Geminiviridae family) represent a severe constraint to agriculture worldwide. As ssDNA viruses that replicate in the nuclei of infected cells, the nascent viral DNA has to move to the cytoplasm and then to the adjacent cell to cause disease. The begomovirus nuclear shuttle protein (NSP) assists the intracellular transport of viral DNA from the nucleus to the cytoplasm and cooperates with the movement protein (MP) for the cell-to-cell translocation of viral DNA to uninfected cells. As a facilitator of intra- and intercellular transport of viral DNA, NSP is predicted to associate with host proteins from the nuclear export machinery, the intracytoplasmic active transport system, and the cell-to-cell transport complex. Furthermore, NSP functions as a virulence factor that suppresses antiviral immunity against begomoviruses. In this review, we focus on the protein-protein network that converges on NSP with a high degree of centrality and forms an immune hub against begomoviruses. We also describe the compatible host functions hijacked by NSP to promote the nucleocytoplasmic and intracytoplasmic movement of viral DNA. Finally, we discuss the NSP virulence function as a suppressor of the recently described NSP-interacting kinase 1 (NIK1)-mediated antiviral immunity. Understanding the NSP-host protein-protein interaction (PPI) network will probably pave the way for strategies to generate more durable resistance against begomoviruses.

Engineering resistance against geminiviruses: A review of suppressed natural defenses and the use of RNAi and the CRISPR/Cas system.

The Geminiviridae family is one of the most successful and largest families of plant viruses that infect a large variety of important dicotyledonous and monocotyledonous crops and cause significant yield losses worldwide. This broad spectrum of host range is only possible because geminiviruses have evolved sophisticated strategies to overcome the arsenal of antiviral defenses in such diverse plant species. In addition, geminiviruses evolve rapidly through recombination and pseudo-recombination to naturally create a great diversity of virus species with divergent genome sequences giving the virus an advantage over the host recognition system. Therefore, it is not surprising that efficient molecular strategies to combat geminivirus infection under open field conditions have not been fully addressed. In this review, we present the anti-geminiviral arsenal of plant defenses, the evolved virulence strategies of geminiviruses to overcome these plant defenses and the most recent strategies that have been engineered for transgenic resistance. Although, the in vitro reactivation of suppressed natural defenses as well as the use of RNAi and CRISPR/Cas systems hold the potential for achieving broad-range resistance and/or immunity, potential drawbacks have been associated with each case.

The receptor-like kinase NIK1 targets FLS2/BAK1 immune complex and inversely modulates antiviral and antibacterial immunity.

Plants deploy various immune receptors to recognize pathogens and defend themselves. Crosstalk may happen among receptor-mediated signal transduction pathways in the same host during simultaneous infection of different pathogens. However, the related function of the receptor-like kinases (RLKs) in thwarting different pathogens remains elusive. Here, we report that NIK1, which positively regulates plant antiviral immunity, acts as an important negative regulator of antibacterial immunity. nik1 plants exhibit dwarfed morphology, enhanced disease resistance to bacteria and increased PAMP-triggered immunity (PTI) responses, which are restored by NIK1 reintroduction. Additionally, NIK1 negatively regulates the formation of the FLS2/BAK1 complex. The interaction between NIK1 and FLS2/BAK1 is enhanced upon flg22 perception, revealing a novel PTI regulatory mechanism by an RLK. Furthermore, flg22 perception induces NIK1 and RPL10A phosphorylation in vivo, activating antiviral signalling. The NIK1-mediated inverse modulation of antiviral and antibacterial immunity may allow bacteria and viruses to activate host immune responses against each other.

A WW Domain-Containing Protein Forms Immune Nuclear Bodies against Begomoviruses.

The bipartite begomoviruses (Geminiviridae family), which are DNA viruses that replicate in the nucleus of infected cells, encode the nuclear shuttle protein (NSP) to facilitate the translocation of viral DNA from the nucleus to the cytoplasm via nuclear pores. This intracellular trafficking of NSP-DNA complexes is accessorized by the NSP-interacting guanosine triphosphatase (NIG) at the cytosolic side. Here, we report the nuclear redistribution of NIG by AtWWP1, a WW domain-containing protein that forms immune nuclear bodies (NBs) against begomoviruses. We demonstrated that AtWWP1 relocates NIG from the cytoplasm to the nucleus where it is confined to AtWWP1-NBs, suggesting that the NIG-AtWWP1 interaction may interfere with the NIG pro-viral function associated with its cytosolic localization. Consistent with this assumption, loss of AtWWP1 function cuased plants more susceptible to begomovirus infection, whereas overexpression of AtWWP1 enhanced plant resistance to begomovirus. Furthermore, we found that a mutant version of AtWWP1 defective for NB formation was no longer capable of interacting with and relocating NIG to the nucleus and lost its immune function against begomovirus. The antiviral function of AtWWP1-NBs, however, could be antagonized by viral infection that induced either the disruption or a decrease in the number of AtWWP1-NBs. Collectively, these results led us to propose that AtWWP1 organizes nuclear structures into nuclear foci, which provide intrinsic immunity against begomovirus infection.

A new TRAF-like protein from B. oleracea ssp. botrytis with lectin activity and its effect on macrophages.

Lectins are involved in a wide range of biological mechanisms, like immunomodulatory agent able to activate the innate immunity. In this study, we purified and characterized a new lectin from cauliflower (Brassica oleracea ssp. botrytis - BOL) by three sequential chromatographic steps and confirmed the purity by SDS-PAGE. Additionally, we evaluated the role of the lectin in innate immunity by a phagocytosis assay, production of H2O2 and NO. BOL was characterized like a non-glycosylated protein that showed a molecular mass of ∼34kDa in SDS-PAGE. Its N-terminal sequence (ETRAFREERPSSKIVTIAG) did not reveal any similarity to the other lectins; nevertheless, it showed 100% homology to a putative TRAF-like protein from Brassica rapa and Brassica napus. This is a first report of the TRAF-protein with lectinic activity. The BOL retained its complete hemagglutination activity from 4°C up to 60°C, with stability being more apparent between pH 7.0 and 8.0. Moreover, the lectin was able to stimulate phagocytosis and induce the production of H2O2 and NO. Therefore, BOL can be explored as an immunomodulatory agent by being able to activate the innate immunity and favor antigen removal.

Adaptation of image cytometry methodology for DNA ploidy analysis of cervical epithelium samples: a pilot study.

OBJECTIVE: To determine DNA ploidy in the cervical specimens of patients revealing a suspicion of cancer by image analysis performed by using a combination of commercial analysis software, conventional microscopy, and certified filters. MATERIALS AND METHODS: This study followed a prospective design. Cervical samples were obtained from 20 patients undergoing routine screening in the Gynecologic-Oncology Unit of the University Hospital of the Federal University of Minas Gerais, Brazil. Three slides were prepared for each case and the DNA content was determined by image cytometry, post Feulgen staining. DNA ploidy, as well as events exceeding 5C and 9C, was assessed according to the guidelines and algorithms prescribed for diagnostic interpretation by the European Society for Analytical Cellular Pathology. RESULTS: By employing the adapted tool, identification of the lesions with euploid and aneuploid profiles was possible. Abnormal DNA content was found in 65% of the cases (13/20), with 45% (9/20) presenting nuclei with >5C content and 20% (4/20) with >9C content. In the analyses conducted in this study, the coefficient of variation with respect to DNA quantity was lower than the 5% threshold recommended by the European Society for Analytical Cellular Pathology. CONCLUSION: Image cytometry of the cervical specimens revealed DNA aneuploidy, most probably resulting from chromosomal alterations and appearing as precancerous lesions in 65% of the cases. The adaptations implemented in this study, enabled the DNA-image cytometry to become more accessible, enhancing its extended use as an adjuvant strategy for the early screening of the cervical epithelium samples during routine analyses.