Predation risk varies on a moment-to-moment basis, through day and night, lunar and seasonal cycles, and over evolutionary time. Hence, it is adaptive for prey animals to exhibit environment-specific ...behaviour, morphology, and (or) life-history traits. Herein, the effects of temporally varying predation risk on growth, behaviour, morphology, and life-history traits of larval Indian Skipper Frogs (Euphlyctis cyanophlyctis (Schneider, 1799)) were studied by exposing them to no risk, continuous, predictable, and unpredictable risks at different time points. Our results show that larval E. cyanophlyctis could learn the temporal pattern of risk leading to weaker behavioural responses under predictable risk and stronger responses to unpredictable risk. Temporally varying predation risk had a significant impact on tadpole morphology. Tadpoles facing continuous risk had narrow tail muscles. Tadpoles facing predictable risk during the day were heavy with wide and deep tail muscles, whereas those facing predictable risk at night had long tails. Tadpoles facing unpredictable risk were heavy with narrow tail muscles. Metamorphic traits of E. cyanophlyctis were also affected by the temporal variation in predation risk. Tadpoles facing predictable risk during the day emerged at the largest size. However, tadpoles facing predictable risk at night and unpredictable risk metamorphosed earlier, whereas those facing continuous risk metamorphosed later.
Early life experiences can have latent effects, which could manifest at a later stage of life history. Though the carryover effects of predation on the behaviour of prey are well-known, the ...integrative effects of predation on the growth, behaviour, and morphology of prey are less known. Hence, we used early (Gosner stages 10–14) and late (stages 15–19) embryonic stages of
Euphlyctis cyanophlyctis
to determine the carryover effects of predation risk on larval growth, behaviour, morphology, and metamorphic traits. Early and late embryonic stages were exposed to cues of predation risk to assess their antipredator responses later during larval life and at metamorphosis. The results show that embryonic exposure to cues of predation risk elicits antipredator behavioural responses towards kairomones of the dragonfly nymphs at the larval stage. Late embryonic stages exposed to cues of predation risk grew faster as larvae and displayed stronger antipredator responses than those exposed during early embryonic stages. Further, early embryonic stages facing cues of predation risk developed narrow bodies and longer tails as tadpoles. However, late embryonic stages facing cues of predation risk accrued greater body mass had narrow tails with greater tailfin heights and deeper tail muscles as tadpoles. The carryover effects of embryonic exposure to cues of predation risk were also apparent at metamorphosis. Embryos exposed during early stages metamorphosed earlier with larger body size. In contrast, embryos exposed to cues of predation risk at later stages metamorphosed earlier with larger length. Thus, the results of our study suggest that embryonic exposure to cues of larval predation induces latent behavioural and developmental carryover effects similar to those displayed by tadpoles facing predation risk.
Significant statement
Recognizing early life dangers may help animals to respond to such dangers later in their life. In this study, for the first time, we show the integrative effects of embryonic exposure to cues of predation risk on growth, behaviour, morphology and life history traits of larval life of the skipper frogs. In the skipper frogs, embryonic exposure to cues of predation risk induces behavioural and developmental effects similar to those shown by tadpoles facing predation risk.
In nature, many microbes secrete mixtures of glycoside hydrolases, oxidoreductases, and accessory enzymes to deconstruct polysaccharides and lignin in plants. These enzymes are often decorated with ...N- and O-glycosylation, the roles of which have been broadly attributed to protection from proteolysis, as the extracellular milieu is an aggressive environment. Glycosylation has been shown to sometimes affect activity, but these effects are not fully understood. Here, we examine N- and O-glycosylation on a model, multimodular glycoside hydrolase family 7 cellobiohydrolase (Cel7A), which exhibits an O-glycosylated carbohydrate-binding module (CBM) and an O-glycosylated linker connected to an N- and O-glycosylated catalytic domain (CD)—a domain architecture common to many biomass-degrading enzymes. We report consensus maps for Cel7A glycosylation that include glycan sites and motifs. Additionally, we examine the roles of glycans on activity, substrate binding, and thermal and proteolytic stability. N-glycan knockouts on the CD demonstrate that N-glycosylation has little impact on cellulose conversion or binding, but does have major stability impacts. O-glycans on the CBM have little impact on binding, proteolysis, or activity in the whole-enzyme context. However, linker O-glycans greatly impact cellulose conversion via their contribution to proteolysis resistance. Molecular simulations predict an additional role for linker O-glycans, namely that they are responsible for maintaining separation between ordered domains when Cel7A is engaged on cellulose, as models predict α-helix formation and decreased cellulose interaction for the nonglycosylated linker. Overall, this study reveals key roles for N- and O-glycosylation that are likely broadly applicable to other plant cell-wall–degrading enzymes.
The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce ...protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.
Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C‐terminal residues of the gD ectodomain are ...essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C‐terminal residues. The structure reveals that the C‐terminus is anchored near the N‐terminal region and masks receptor‐binding sites. Locking the C‐terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C‐terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C‐terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.
It remains challenging to produce decisive vaccines against MUC1, a tumor-associated antigen widely expressed by pancreas, breast and other tumors. Employing clinically relevant mouse models, we ...ruled out such causes as irreversible T-cell tolerance, inadequate avidity, and failure of T-cells to recognize aberrantly glycosylated tumor MUC1. Instead, every tested MUC1 preparation, even non-glycosylated synthetic 9mer peptides, induced interferon gamma-producing CD4(+) and CD8(+) T-cells that recognized glycosylated variants including tumor-associated MUC1. Vaccination with synthetic peptides conferred protection as long as vaccination was repeated post tumor challenge. Failure to revaccinate post challenge was associated with down-regulated tumor MUC1 and MHC molecules. Surprisingly, direct admixture of MUC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC1 immunoediting, whereas ex vivo activation of the hyperimmune T-cells prior to tumor admixture rendered them curative. Therefore, surrogate T-cell preactivation outside the tumor bed, either in culture or by repetitive vaccination, can overcome tumor escape.
Introduction
Autism spectrum disorder (ASD) is among the most common and pervasive neurodevelopmental disorders. Yet, despite decades of research, the neurobiology of ASD is still poorly understood, ...as inconsistent findings preclude the identification of robust and interpretable neurobiological markers and predictors of clinical symptoms.
Objectives
Identify robust and interpretable dynamic brain markers that distinguish children with ASD from typically-developing (TD) children and predict clinical symptom severity.
Methods
We leverage multiple functional brain imaging cohorts (ABIDE, Stanford; N = 1004) and exciting recent advances in explainable artificial intelligence (xAI), to develop a novel multivariate time series deep neural network model that extracts informative brain dynamics features that accurately distinguish between ASD and TD children, and predict clinical symptom severity.
Results
Our model achieved consistently high classification accuracies in cross-validation analysis of data from the ABIDE cohort. Crucially, despite the differences in symptom profiles, age, and data acquisition protocols, our model also accurately classified data from an independent Stanford cohort without additional training. xAI analyses revealed that brain features associated with the default mode network, and the human voice/face processing and communication systems, most clearly distinguished ASD from TD children in both cohorts. Furthermore, the posterior cingulate cortex emerged as robust predictor of the severity of social and communication deficits in ASD in both cohorts.
Conclusions
Our findings, replicated across two independent cohorts, reveal robust and neurobiologically interpretable brain features that detect ASD and predict core phenotypic features of ASD, and have the potential to transform our understanding of the etiology and treatment of the disorder.
Disclosure
No significant relationships.
Successful coexistence with predators depends on the ability of prey to strike a balance between the costs of predator avoidance and the benefits of foraging and reproducing as there is a trade-off ...between these activities. Prey animals can balance this trade-off by responding to predation risk in a manner that matches the intensity of risk posed by the predator, which is known as the threat-sensitive predator avoidance hypothesis. To test this hypothesis, we exposed larval Indian skipper frogs (
Euphlyctis cyanophlyctis
) to different intensities of predation risk by increasing the number of predators and the amount of biomass consumed and recorded their behaviour, morphology, and metamorphic traits. We also quantified the whole-body corticosterone to assess the physiological basis of alterations in morphology, behaviour, and life-history traits. The results indicate that behavioural responses of larval skipper frogs increased with the intensity of risk conforming to the predictions of the threat-sensitivity hypothesis. However, the morphological responses did not vary with the intensity of risk and hence did not support the predictions of the hypothesis. Interestingly, tadpoles facing a higher level of predation risk metamorphosed at the largest size, but with increased larval duration. At the physiological level, corticosterone levels increased with increases in the intensity of risk. Thus, our results suggest that certain antipredator responses may vary with the intensity of risk while others may not. Further, the results of our study also show an association between physiological and behavioural responses of larval
E. cyanophlyctis
to predation risk. More importantly, we show that larval skipper frogs can assess the intensity of predation risk through threat-sensitive learning by associating conspecific alarm cues with odours of dragonfly nymphs.
We present a high-resolution miniature, light-weight fluorescence microscope with electrowetting lens and onboard CMOS for high resolution volumetric imaging and structured illumination for rejection ...of out-of-focus and scattered light. The miniature microscope (SIMscope3D) delivers structured light using a coherent fiber bundle to obtain optical sectioning with an axial resolution of 18 µm. Volumetric imaging of eGFP labeled cells in fixed mouse brain tissue at depths up to 260 µm is demonstrated. The functionality of SIMscope3D to provide background free 3D imaging is shown by recording time series of microglia dynamics in awake mice at depths up to 120 µm in the brain.
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