\u3ci\u3eSUB1A\u3c/i\u3e-mediated submergence tolerance response in rice involves differential regulation of the brassinosteroid pathway

Submergence 1A (SUB1A), is an ethylene response factor (ERF) that confers submergence tolerance in rice (Oryza sativa) via limiting shoot elongation during the inundation period. SUB1A has been proposed to restrict shoot growth by modulating gibberellic acid (GA) signaling. Our transcriptome analysis indicated that SUB1A differentially regulates genes associated with brassinosteroid (BR) synthesis during submergence. Consistent with the gene expression data, the SUB1A genotype had higher brassinosteroid levels after submergence compared to the intolerant genotype. Tolerance to submergence can be activated in the intolerant genotype by pretreatment with exogenous brassinolide, which results in restricted shoot elongation during submergence. BR induced a GA catabolic gene, resulting in lower GA levels in SUB1A plants. BR treatment also induced the DELLA protein SLR1, a known repressor of GA responses such as shoot elongation. We propose that BR limits GA levels during submergence in the SUB1A rice through a GA catabolic enzyme as part of an early response and may repress GA responses by inducing SLR1 after several days of submergence. Our results suggest that BR biosynthesis is regulated in a SUB1A-dependent manner during submergence and is involved in modulating the GA signaling and homeostasis

A role for the RabA4b effector protein PI-4Kβ1 in polarized expansion of root hair cells in Arabidopsis thaliana

The RabA4b GTPase labels a novel, trans-Golgi network compartment displaying a developmentally regulated polar distribution in growing Arabidopsis thaliana root hair cells. GTP bound RabA4b selectively recruits the plant phosphatidylinositol 4-OH kinase, PI-4Kβ1, but not members of other PI-4K families. PI-4Kβ1 colocalizes with RabA4b on tip-localized membranes in growing root hairs, and mutant plants in which both the PI-4Kβ1 and -4Kβ2 genes are disrupted display aberrant root hair morphologies. PI-4Kβ1 interacts with RabA4b through a novel homology domain, specific to eukaryotic type IIIβ PI-4Ks, and PI-4Kβ1 also interacts with a Ca2+ sensor, AtCBL1, through its NH2 terminus. We propose that RabA4b recruitment of PI-4Kβ1 results in Ca2+-dependent generation of PI-4P on this compartment, providing a link between Ca2+ and PI-4,5P2–dependent signals during the polarized secretion of cell wall components in tip-growing root hair cells

Human NK cells confer protection against HIV-1 infection in humanized mice

The role of NK cells against HIV-1 infections remains to be elucidated in vivo. While humanized mouse models potentially could be used to directly evaluate human NK cell responses during HIV-1 infection, improved functional development of human NK cells in these hosts is needed. Here, we report the humanized MISTRG-6-15 mouse model, in which NK cells were quick to expand and exhibit degranulation, cytotoxicity, and proinflammatory cytokine production in nonlymphoid organs upon HIV-1 infection but had reduced functionality in lymphoid organs. Although HIV-1 infection induced functional impairment of NK cells, antiretroviral therapy reinvigorated NK cells in response to HIV-1 rebound after analytic treatment interruption. Moreover, a broadly neutralizing antibody, PGT121, enhanced NK cell function in vivo, consistent with antibody-dependent cellular cytotoxicity. Monoclonal antibody depletion of NK cells resulted in higher viral loads in multiple nonlymphoid organs. Overall, our results in humanized MISTRG-6-15 mice demonstrated that NK cells provided direct anti-HIV-1 responses in vivo but were limited in their responses in lymphoid organs

Polyclonal epitope mapping reveals temporal dynamics and diversity of human antibody responses to H5N1 vaccination

Novel influenza A virus (IAV) strains elicit recall immune responses to conserved epitopes, making them favorable antigenic choices for universal influenza virus vaccines. Evaluating these immunogens requires a thorough understanding of the antigenic sites targeted by the polyclonal antibody (pAb) response, which single-particle electron microscopy (EM) can sensitively detect. In this study, we employ EM polyclonal epitope mapping (EMPEM) to extensively characterize the pAb response to hemagglutinin (HA) after H5N1 immunization in humans. Cross-reactive pAbs originating from memory B cells immediately bound the stem of HA and persisted for more than a year after vaccination. In contrast, de novo pAb responses to multiple sites on the head of HA, targeting previously determined key neutralizing sites on H5 HA, expanded after the second immunization and waned quickly. Thus, EMPEM provides a robust tool for comprehensively tracking the specificity and durability of immune responses elicited by novel universal influenza vaccine candidates

Repeat modules and N-linked glycans define structure and antigenicity of a critical enterotoxigenic E. coli adhesin

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA directs ETEC-blood group A interactions and stimulates adaptive immunity, we mutated EtpA, mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) and monoclonal antibodies (mAbs) from vaccinated mice and ETEC-infected volunteers, and determined structures of antibody-EtpA complexes by cryo-electron microscopy. Both bgA and mAbs that inhibited EtpA-bgA interactions and ETEC adhesion, bound to the C-terminal repeat domain highlighting this region as crucial for ETEC pathogen-host interaction. MS analysis uncovered extensive and heterogeneous N-linked glycosylation of EtpA and cryo-EM structures revealed that mAbs directly engage these unique glycan containing epitopes. Finally, electron microscopy-based polyclonal epitope mapping revealed antibodies targeting numerous distinct epitopes on N and C-terminal domains, suggesting that EtpA vaccination generates responses against neutralizing and decoy regions of the molecule. Collectively, we anticipate that these data will inform our general understanding of pathogen-host glycan interactions and adaptive immunity relevant to rational vaccine subunit design

Maturation of germinal center B cells after influenza virus vaccination in humans

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells

Influenza vaccination stimulates maturation of the human T follicular helper cell response

The differentiation and specificity of human CD

A review of the Angolan House snakes, genus Boaedon Duméril, Bibron and Duméril (1854) (Serpentes: Lamprophiidae), with description of three new species in the Boaedon fuliginosus (Boie, 1827) species complex

An integrative taxonomic review of the genus Boaedon in Angola is provided. A molecular phylogeny, based on 99 genetic samples for which the mitochondrial markers 16S rRNA have been sequenced, reveals 23 monophyletic species-level groups in Africa and indicates the presence of nine species in Angola. Based on both phylogenetic and morphological data, we revalidate and designate a neotype for B. angolensis, describe three new species for Angola (e.g. B. bocagei sp. nov., B. branchi sp. nov., and B. fradei sp. nov.), revalidate B. variegatus from its synonymy with B. lineatus and designate a lectotype for this taxon, and identify B. lineatus var. lineolatus as a junior synonym of B. variegatus. The taxonomic status of the recently described B. paralineatus from Central Africa is discussed with respect to the more inclusive B. lineatus group. Moreover, we report on a new country record for Angola, namely B. mentalis, which we elevate here to full species and discuss the taxonomic status of this species in southern Africa. Finally, we provide an identification key and updated distribution maps for all Boaedon species occurring in Angola, including the Cabinda enclave.The National Science Foundation of the United States, the JRS Biodiversity Foundation, FCT, the National Geographic Okavango Wilderness Project and the Wild Bird Trust National Geographic Okavango Wilderness Project.https://www.tandfonline.com/loi/ther202021-07-08hj2021Zoology and Entomolog

The Influence of Feedback on Task-Switching Performance:A Drift Diffusion Modeling Account

Task-switching is an important cognitive skill that facilitates our ability to choose appropriate behavior in a varied and changing environment. Task-switching training studies have sought to improve this ability by practicing switching between multiple tasks. However, an efficacious training paradigm has been difficult to develop in part due to findings that small differences in task parameters influence switching behavior in a non-trivial manner. Here, for the first time we employ the Drift Diffusion Model (DDM) to understand the influence of feedback on task-switching and investigate how drift diffusion parameters change over the course of task switch training. We trained 316 participants on a simple task where they alternated sorting stimuli by color or by shape. Feedback differed in six different ways between subjects groups, ranging from No Feedback (NFB) to a variety of manipulations addressing trial-wise vs. Block Feedback (BFB), rewards vs. punishments, payment bonuses and different payouts depending upon the trial type (switch/non-switch). While overall performance was found to be affected by feedback, no effect of feedback was found on task-switching learning. Drift Diffusion Modeling revealed that the reductions in reaction time (RT) switch cost over the course of training were driven by a continually decreasing decision boundary. Furthermore, feedback effects on RT switch cost were also driven by differences in decision boundary, but not in drift rate. These results reveal that participants systematically modified their task-switching performance without yielding an overall gain in performance

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases