Mccaffreykromann8398

Animals must selectively attend to relevant stimuli and avoid being distracted by unimportant stimuli. Jumping spiders (Salticidae) do this by coordinating eyes with different capabilities. Objects are examined by a pair of high-acuity principal eyes, whose narrow field of view is compensated for by retinal movements. The principal eyes overlap in field of view with motion-sensitive anterior-lateral eyes (ALEs), which direct their gaze to new stimuli. Using a salticid-specific eyetracker, we monitored the gaze direction of the principal eyes as they examined a primary stimulus. We then presented a distractor stimulus visible only to the ALEs and observed whether the principal eyes reflexively shifted their gaze to it or whether this response was flexible. Whether spiders redirected their gaze to the distractor depended on properties of both the primary and distractor stimuli. This flexibility suggests that higher-order processing occurs in the management of the attention of the principal eyes.Heat tolerance of heart rate in fish is suggested to be limited by impaired electrical excitation of the ventricle due to the antagonistic effects of high temperature on Na+ (INa) and K+ (IK1) ion currents (INa is depressed at high temperatures while IK1 is resistant to them). To examine the role of Na+ channel proteins in heat tolerance of INa, we compared temperature dependencies of zebrafish (Danio rerio, warm-dwelling subtropical species) and rainbow trout (Oncorhynchus mykiss, cold-active temperate species) ventricular INa, and INa generated by the cloned zebrafish and rainbow trout NaV1.4 and NaV1.5 Na+ channels in human embryonic kidney (HEK) cells. GSK'872 Whole-cell patch-clamp recordings showed that zebrafish ventricular INa has better heat tolerance and slower inactivation kinetics than rainbow trout ventricular INa. In contrast, heat tolerance and inactivation kinetics of zebrafish and rainbow trout NaV1.4 channels are similar when expressed in the identical cellular environment of HEK cells. The same applies to NaV1.5 channels. These findings indicate that thermal adaptation of ventricular INa is largely achieved by differential expression of Na+ channel alpha subunits zebrafish that tolerate higher temperatures mainly express the slower NaV1.5 isoform, while rainbow trout that prefer cold waters mainly express the faster NaV1.4 isoform. Differences in elasticity (stiffness) of the lipid bilayer and/or accessory protein subunits of the channel assembly may also be involved in thermal adaptation of INa. The results are consistent with the hypothesis that slow Na+ channel kinetics are associated with increased heat tolerance of cardiac excitation.In the wild, being able to recognize and remember specific locations related to food sources and the associated attributes of landmarks is a cognitive trait important for survival. In the present work, we show that the crab Neohelice granulata can be trained to associate a specific environment with an appetitive reward in a conditioned place preference task. After a single training trial, when the crabs were presented with a food pellet in the target quadrant of the training arena, they were able to form a long-term memory related to the event. This memory was evident at least 24 h after training and was protein synthesis dependent. Importantly, the target area of the arena proved to be a non-neutral environment, given that animals initially avoided the target quadrant. In the present work, we introduce for the first time an associative one-trial memory paradigm including a conditioned stimulus with a clear valence performed in a crustacean.Many expressions of phenotype, such as physiological performance, integrate multiple underlying traits to function. Linking component traits to adaptive physiology thus gives insight into mechanisms of selection acting on performance. Genome size (C-value) is a trait that influences physiology in multiple taxa by exerting a nucleotypic effect, constraining cell size and cellular physiology such that whole-organism mass-specific metabolism is reduced with increasing C-value. We tested for this mechanism of C-value function acting in lungless salamanders, plus an unexplored potential mechanism of C-value effects constraining water transport across the body surface to influence cutaneous water loss rates. We found no evidence for a nucleotypic effect on metabolic rates, but we demonstrate a relationship between C-value and water loss physiology. Under warmer experimental conditions, C-value was inversely correlated with water loss and positively correlated with resistance to water loss, which demonstrated adaptive plasticity at higher temperatures. We hypothesize that this pattern results from differences in cell size constraining diffusion and evaporation of water from the skin under warm conditions when cutaneous perfusion is reduced. Testing this hypothesis may confirm a previously unappreciated adaptive role for C-value variation in this group, and reveals the possibility that genome size influences physiological exchange across transport barriers more broadly.High-quality metadata annotations for data hosted in large public repositories are essential for research reproducibility and for conducting fast, powerful and scalable meta-analyses. Currently, a majority of sequencing samples in the National Center for Biotechnology Information's Sequence Read Archive (SRA) are missing metadata across several categories. In an effort to improve the metadata coverage of these samples, we leveraged almost 44 million attribute-value pairs from SRA BioSample to train a scalable, recurrent neural network that predicts missing metadata via named entity recognition (NER). link2 The network was first trained to classify short text phrases according to 11 metadata categories and achieved an overall accuracy and area under the receiver operating characteristic curve of 85.2% and 0.977, respectively. We then applied our classifier to predict 11 metadata categories from the longer TITLE attribute of samples, evaluating performance on a set of samples withheld from model training. Prediction accuracies were high when extracting sample Genus/Species (94.85%), Condition/Disease (95.65%) and Strain (82.03%) from TITLEs, with lower accuracies and lack of predictions for other categories highlighting multiple issues with the current metadata annotations in BioSample. These results indicate the utility of recurrent neural networks for NER-based metadata prediction and the potential for models such as the one presented here to increase metadata coverage in BioSample while minimizing the need for manual curation. Database URL https//github.com/cartercompbio/PredictMEE.Activation of inflammation by lipopolysaccharide (LPS) is an important innate immune response. Here we investigated the contribution of caspases to the LPS-mediated inflammatory response and discovered distinctive temporal roles of RIPK1 in mediating proinflammatory cytokine production when caspases are inhibited. We propose a biphasic model that differentiates the role of RIPK1 in early versus late phase. The early production of proinflammation cytokines stimulated by LPS with caspase inhibition is mediated by the NF-κB pathway that requires the scaffold function of RIPK1 but is kinase independent. Autocrine production of TNFα in the late phase promotes the formation of a novel TNFR1-associated complex with activated RIPK1, FADD, caspase-8, and key mediators of NF-κB signaling. The production of proinflammatory cytokines in the late phase can be blocked by RIPK1 kinase inhibitor Nec-1s. Our study demonstrates a mechanism by which the activation of RIPK1 promotes its own scaffold function to regulate the NF-κB-mediated proinflammatory cytokine production that is negatively regulated by caspases to restrain inflammatory signaling.Rac1 GTPase is hyperactivated in tumors and contributes to malignancy. Rac1 disruption of junctions requires its effector PAK1, but the precise mechanisms are unknown. link3 Here, we show that E-cadherin is internalized via micropinocytosis in a PAK1-dependent manner without catenin dissociation and degradation. In addition to internalization, PAK1 regulates E-cadherin transport by fine-tuning Rab small GTPase function. PAK1 phosphorylates a core Rab regulator, RabGDIβ, but not RabGDIα. Phosphorylated RabGDIβ preferentially associates with Rab5 and Rab11, which is predicted to promote Rab retrieval from membranes. Consistent with this hypothesis, Rab11 is activated by Rac1, and inhibition of Rab11 function partially rescues E-cadherin destabilization. Thus, Rac1 activation reduces surface cadherin levels as a net result of higher bulk flow of membrane uptake that counteracts Rab11-dependent E-cadherin delivery to junctions (recycling and/or exocytosis). This unique small GTPase crosstalk has an impact on Rac1 and PAK1 regulation of membrane remodeling during epithelial dedifferentiation, adhesion, and motility.

In 2018, only half of US women obtained all evidence-based cancer screenings. This proportion may have declined during the COVID-19 pandemic because of social distancing, high-risk factors, and fear.

To evaluate optimal screening strategies in women who obtain some, but not all, US Preventive Services Task Force (USPSTF)-recommended cancer screenings.

This modeling study was conducted from January 31, 2017, to July 20, 2020, and used 4 validated mathematical models from the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network using data from 20 million simulated women born in 1965 in the US.

Forty-five screening strategies were modeled that combined breast, cervical, colorectal, and/or lung cancer (LC) screenings; restricted to 1, 2, 3 or 4 screenings per year; or all eligible screenings once every 5 years.

Modeled life-years gained from restricted cancer screenings as a fraction of those attainable from full compliance with USPSTF recommendations (maximum benefits). Resgs per year was annual LC screening and alternating fecal immunochemical test with mammography (skipping mammograms when due for cervical cancer screening, 97% of maximum benefits). If adherence in a population of LC-eligible women obtaining 2 screenings per year were to increase by 1% to 2% (depending on the screening test), this model suggests that it would achieve the same benefit as USPSTF recommendations at 2018 adherence rates.

This modeling study of 45 cancer screening strategies suggests that women who are noncompliant with cancer screening guidelines may be able to reduce USPSTF-recommended screening intensity with minimal reduction in overall benefits.

This modeling study of 45 cancer screening strategies suggests that women who are noncompliant with cancer screening guidelines may be able to reduce USPSTF-recommended screening intensity with minimal reduction in overall benefits.For the large array of self-peptide/MHC class II (pMHC-II) complexes displayed in the body, it is unclear whether CD4+ T cell tolerance must be imparted for each individual complex or whether pMHC-II-nonspecific bystander mechanisms are sufficient to confer tolerance by acting broadly on T cells reactive to multiple self-pMHC-II ligands. Here, via reconstitution of T cell-deficient mice, we demonstrate that altered T cell selection on a single prostate-specific self-pMHC-II ligand renders recipient mice susceptible to prostate-specific T cell infiltration. Mechanistically, this self-pMHC-II complex is required for directing antigen-specific cells into the Foxp3+ regulatory T cell lineage but does not induce clonal deletion to a measurable extent. Thus, our data demonstrate that polyclonal T reg cells are unable to functionally compensate for a breach in tolerance to a single self-pMHC-II complex in this setting, revealing vulnerabilities in antigen-nonspecific bystander mechanisms of immune tolerance.