Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice

The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane–binding anti-DNA antibody. Basement membrane–binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis

Antibiotic-induced Decreases inthe Levels of Microbial-derivedShort-chain Fatty Acids Correlatewith Increased GastrointestinalColonization of Candida Albicans

Candida albicans is the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemic C. albicans infections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to prevent C. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization of C. albicans. Our results indicate that cefoperazone-treated mice susceptible to C. albicans infection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, using in vivo concentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development of C. albicans in vitro. Collectively, results from this study suggest that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization of C. albicans

A wavelet-based tool for studying non-periodicity

This paper presents a new numerical approach to the study of non-periodicity in signals, which can complement the maximal Lyapunov exponent method for determining chaos transitions of a given dynamical system. The proposed technique is based on the continuous wavelet transform and the wavelet multiresolution analysis. A new parameter, the \textit{scale index}, is introduced and interpreted as a measure of the degree of the signal's non-periodicity. This methodology is successfully applied to three classical dynamical systems: the Bonhoeffer-van der Pol oscillator, the logistic map, and the Henon map.Comment: 14 pages, 6 figure

Global Cue Inconsistency Diminishes Learning of Cue Validity

We present a novel two-stage probabilistic learning task that examines the participants’ ability to learn and utilize valid cues across several levels of probabilistic feedback. In the first stage, participants sample from one of three cues that gives predictive information about the outcome of the second stage. Participants are rewarded for correct prediction of the outcome in stage two. Only one of the three cues gives valid predictive information and thus participants can maximise their reward by learning to sample from the valid cue. The validity of this predictive information, however, is reinforced across several levels of probabilistic feedback. A second manipulation involved changing the consistency of the predictive information in stage one and the outcome in stage two. The results show that participants, with higher probabilistic feedback, learned to utilise the valid cue. In inconsistent task conditions, however, participants were significantly less successful in utilising higher validity cues. We interpret this result as implying that learning in probabilistic categorization is based on developing a representation of the task that allows for goal-directed action

Pursuing the Half Empty Question : Biology Undergraduates\u27 Differential Engagement in a Brief Relevance Writing Intervention

Whereas relevance-writing interventions have shown effects on students’ achievement, a persistent finding is that interventions benefit students with low, but not high, outcome expectancies—a phenomenon that Schwartz et al. (2016) termed the half empty question. In the current mixed-methods study, we investigated the role of undergraduate students’ patterns of engagement in a relevance-writing intervention and their relations to biology course achievement. Ninety-six students who were administered four relevance writing assignments were found to manifest two patterns: Students who completed at least 50% of the intervention in a timely manner outperformed those who completed less-then-50% or completed it late, regardless of their pre-intervention motivation. A closer look into individual students’ patterns showed diverse perceptions about the relevance-writing tasks

Modulation of the F-actin cytoskeleton by c-Abl tyrosine kinase in cell spreading and neurite extension

The nonreceptor tyrosine kinase encoded by the c-Abl gene has the unique feature of an F-actin binding domain (FABD). Purified c-Abl tyrosine kinase is inhibited by F-actin, and this inhibition can be relieved through mutation of its FABD. The c-Abl kinase is activated by physiological signals that also regulate the actin cytoskeleton. We show here that c-Abl stimulated the formation of actin microspikes in fibroblasts spreading on fibronectin. This function of c-Abl is dependent on kinase activity and is not shared by c-Src tyrosine kinase. The Abl-dependent F-actin microspikes occurred under conditions where the Rho-family GTPases were inhibited. The FABD-mutated c-Abl, which is active in detached fibroblasts, stimulated F-actin microspikes independent of cell attachment. Moreover, FABD-mutated c-Abl stimulated the formation of F-actin branches in neurites of rat embryonic cortical neurons. The reciprocal regulation between F-actin and the c-Abl tyrosine kinase may provide a self-limiting mechanism in the control of actin cytoskeleton dynamics

Planet Hunters. VI: An Independent Characterization of KOI-351 and Several Long Period Planet Candidates from the Kepler Archival Data

We report the discovery of 14 new transiting planet candidates in the Kepler field from the Planet Hunters citizen science program. None of these candidates overlapped with Kepler Objects of Interest (KOIs) at the time of submission. We report the discovery of one more addition to the six planet candidate system around KOI-351, making it the only seven planet candidate system from Kepler. Additionally, KOI-351 bears some resemblance to our own solar system, with the inner five planets ranging from Earth to mini-Neptune radii and the outer planets being gas giants; however, this system is very compact, with all seven planet candidates orbiting $\lesssim 1$ AU from their host star. A Hill stability test and an orbital integration of the system shows that the system is stable. Furthermore, we significantly add to the population of long period transiting planets; periods range from 124-904 days, eight of them more than one Earth year long. Seven of these 14 candidates reside in their host star's habitable zone.Comment: 27 pages, 6 figures, 5 tables, Accepted to AJ (in press) (updated title from original astro-ph submission

Micro(nano)plastic toxicity and health effects: Special issue guest editorial

Microplastics (MPs) and nanoplastics (NPs), collectively termed “Micro(nano)plastics [MNPs]” in the special issue, compose the vast majority of plastic contaminants. MPs have become ubiquitous in the global environment (Walker, 2021, Allen et al., 2022) and NPs have also been reported in environmental samples (Cai et al., 2021). MPs have been widely detected in hundreds of animal and plant species (Karbalaei et al., 2019, Litterbase, 2022), including human placentas and blood (Leslie and Depledge, 2020, Prata et al., 2020, Ragusa et al., 2021, Leslie et al., 2022) as MPs are inhaled or consumed via food products and drinking water (Danopoulos et al., 2020, Sequeira et al., 2020, Zhang et al., 2020, Adib et al., 2022). Due to their small sizes, ubiquitous and persistent nature, the potential toxicity and health effects of MNPs have attracted significant attention and spurring rapidly-increasing research efforts (e.g., Guo et al., 2020, Castro-Castellon et al., 2021, Karbalaei et al., 2021, Khoshnamvand et al., 2021, Lahive et al., 2022, Palacio-Cortés et al., 2022). Studies on laboratory animals have mostly focused on aquatic species and have shown accumulation of MNPs in tissues and organs, causing intestinal injuries, increasing oxidative stress, triggering inflammation, neurotoxicity, and impaired development (Castro-Castellon et al., 2021, Karbalaei et al., 2021, Kukkola et al., 2021, Matthews et al., 2021). However, the actual ecological and human health impacts of MNPs are still largely unknown and few published studies have directly investigated the effects of MNPs on humans (Weber et al., 2022). Evaluating the potential adverse ecological and human health effects of MNPs across levels of biological organization has become highly imperative but challenging due to the high heterogeneity of MNPs, unknown environmental concentrations, debated vector effects for associated chemicals, and co-impact with other environmental stressors, such as climate change and other chemical contaminants (Thornton Hampton et al., 2022). Currently, the concentrations of MNPs in the environment may be low, but their increasing inputs are inevitable based on current and projected plastic production data (Borrelle et al., 2020). Therefore, it has become imperative to evaluate the potential ecological and human health impacts of MNPs

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Toll family members bind multiple Spatzle proteins and activate antimicrobial peptide gene expression in Drosophila

The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spatzle (Spz-1), but Drosophila encodes eight other Toll genes and five other Spz genes whose interactions with one another and associated functions are less well understood. Here, we conducted in vitro assays in the Drosophila S2 cell line with the Toll/interleukin-1 receptor (TIR) homology domains of each Toll family member to determine if they can activate a known target of Toll-1, the promoter of the antifungal peptide gene drosomycin. All TIR family members activated the drosomycin promoter, with Toll-1 and Toll-7 TIRs producing the highest activation. We found that the Toll-1 and Toll-7 ectodomains bind Spz-1, -2, and -5 and also vesicular stomatitis virus (VSV) virions, and that Spz-1, -2, -5, and VSV all activated the promoters of drosomycin and several other AMP genes in S2 cells expressing full-length Toll-1 or Toll-7. In vivo experiments indicated that Toll-1 and Toll-7 mutants could be systemically infected with two bacterial species (Enterococcus faecalis and Pseudomonas aeruginosa), the opportunistic fungal pathogen Candida albicans and VSV with different survival in adult females and males compared with wild-type fly survival. Our results suggest that all Toll family members can activate several AMP genes. Our results further indicate that Toll-1 and Toll-7 bind multiple Spz proteins and also VSV, but differentially affect adult survival after systemic infection, potentially because of sex-specific differences in Toll-1 and Toll-7 expression