Distinguishing self from nonself and the onset of defense effector mechanisms upon recognition of pathogens are essential for the survival of all life forms in the animal kingdom. The family of ...nucleotide -binding and oligomeriszation domain-like receptors (NLRs) was first identified in vertebrates and comprises a group of pivotal sensor protein of the innate immune system for microbial cell wall components or danger signals. Here, we provide first evidence that early diverging metazoans have large and complex NLR repertoires. The cnidarian NACHT/NB-ARC genes include novel combinations of domains, and the number of one specific type (NB-ARC and tetratricopeptide repeat containing) in Hydra is particularly large. We characterize the transcript structure and expression patterns of a selected HyNLR, HyNLR type 1 and describe putative interaction partners. In a heterologous expression system, we show induced proximity recruitment of an effector caspase (HyDD-Caspase) to the HyNLR type 1 protein upon oligomerization indicating a potential role of caspase activation downstream of NLR activation in Hydra. These results add substantially to our understanding of the ancestral innate immune repertoire as well as providing the first insights into putative cytoplasmic defense mechanisms at the base of animal evolution.
Background & Aims: Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain. We conducted a prospective study to measure incidence of advanced neoplasia in ...patients within 5.5 years of screening colonoscopy. Methods: Three thousand one hundred twenty-one asymptomatic subjects, age 50 to 75 years, had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs. One thousand one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years. Cohorts were defined by baseline findings. Relative risks for advanced neoplasia within 5.5 years were calculated. Advanced neoplasia was defined as tubular adenoma greater than ≥10 mm, adenoma with villous histology, adenoma with high-grade dysplasia, or invasive cancer. Results: Eight hundred ninety-five (76.4%) patients with neoplasia and 298 subjects (59.5%) without neoplasia at baseline had colonoscopy within 5.5 years; 2.4% of patients with no neoplasia had interval advanced neoplasia. The relative risk in patients with baseline neoplasia was 1.92 (95% CI: 0.83–4.42) with 1 or 2 tubular adenomas <10 mm, 5.01 (95% CI: 2.10–11.96) with 3 or more tubular adenomas <10 mm, 6.40 (95% CI: 2.74–14.94) with tubular adenoma ≥10 mm, 6.05 (95% CI: 2.48–14.71) for villous adenoma, and 6.87 (95% CI: 2.61–18.07) for adenoma with high-grade dysplasia. Conclusions: There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance. Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia.
The relationship between nanoparticle size, charge, shape, and in vivo biodistribution is of great importance for the rational design and selection of intravenously administered nanoparticles. A ...resource that aids in the selection and design of nanomaterials for this purpose would be a valuable tool. Previous literature reviews have examined narrow categories of nanomaterials or have not statistically analyzed a broad range of nanomaterial literature. Here, data regarding the biodistribution of intravenously administered synthetic and organic nanomaterials in animal models from literature available in PubMed is collected. This work outlines the effect of nanoparticle size, charge, shape, animal sex, and animal disease status on biodistribution of intravenously administered nanomaterials. Particle size and charge are found to significantly and independently influence biodistribution to several organs. Finally, animal sex and disease state are observed to function as effect modifiers for biodistribution.
Recent progress in nanomedicine has necessitated an overview of the effect material characteristics such as size, charge, and shape on biodistribution of intravenously delivered nanomaterials. A resource to aid in design and selection of nanoparticles tailored to specific drug delivery aims is a valuable tool for the field. Here, the ways that particular formulations of nanomaterials or sex/disease status alter material biodistribution are briefly outlined.
Physical and social neighborhood attributes may have implications for children's growth and development patterns. The extent to which these attributes are associated with body mass index (BMI) ...trajectories and obesity risk from childhood to adolescence remains understudied.
To examine associations of neighborhood-level measures of opportunity and social vulnerability with trajectories of BMI and obesity risk from birth to adolescence.
This cohort study used data from 54 cohorts (20 677 children) participating in the Environmental Influences on Child Health Outcomes (ECHO) program from January 1, 1995, to January 1, 2022. Participant inclusion required at least 1 geocoded residential address and anthropometric measure (taken at the same time or after the address date) from birth through adolescence. Data were analyzed from February 1 to June 30, 2022.
Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) linked to geocoded residential addresses at birth and in infancy (age range, 0.5-1.5 years), early childhood (age range, 2.0-4.8 years), and mid-childhood (age range, 5.0-9.8 years).
BMI (calculated as weight in kilograms divided by length if aged <2 years or height in meters squared) and obesity (age- and sex-specific BMI ≥95th percentile). Based on nationwide distributions of the COI and SVI, Census tract rankings were grouped into 5 categories: very low (<20th percentile), low (20th percentile to <40th percentile), moderate (40th percentile to <60th percentile), high (60th percentile to <80th percentile), or very high (≥80th percentile) opportunity (COI) or vulnerability (SVI).
Among 20 677 children, 10 747 (52.0%) were male; 12 463 of 20 105 (62.0%) were White, and 16 036 of 20 333 (78.9%) were non-Hispanic. (Some data for race and ethnicity were missing.) Overall, 29.9% of children in the ECHO program resided in areas with the most advantageous characteristics. For example, at birth, 26.7% of children lived in areas with very high COI, and 25.3% lived in areas with very low SVI; in mid-childhood, 30.6% lived in areas with very high COI and 28.4% lived in areas with very low SVI. Linear mixed-effects models revealed that at every life stage, children who resided in areas with higher COI (vs very low COI) had lower mean BMI trajectories and lower risk of obesity from childhood to adolescence, independent of family sociodemographic and prenatal characteristics. For example, among children with obesity at age 10 years, the risk ratio was 0.21 (95% CI, 0.12-0.34) for very high COI at birth, 0.31 (95% CI, 0.20-0.51) for high COI at birth, 0.46 (95% CI, 0.28-0.74) for moderate COI at birth, and 0.53 (95% CI, 0.32-0.86) for low COI at birth. Similar patterns of findings were observed for children who resided in areas with lower SVI (vs very high SVI). For example, among children with obesity at age 10 years, the risk ratio was 0.17 (95% CI, 0.10-0.30) for very low SVI at birth, 0.20 (95% CI, 0.11-0.35) for low SVI at birth, 0.42 (95% CI, 0.24-0.75) for moderate SVI at birth, and 0.43 (95% CI, 0.24-0.76) for high SVI at birth. For both indices, effect estimates for mean BMI difference and obesity risk were larger at an older age of outcome measurement. In addition, exposure to COI or SVI at birth was associated with the most substantial difference in subsequent mean BMI and risk of obesity compared with exposure at later life stages.
In this cohort study, residing in higher-opportunity and lower-vulnerability neighborhoods in early life, especially at birth, was associated with a lower mean BMI trajectory and a lower risk of obesity from childhood to adolescence. Future research should clarify whether initiatives or policies that alter specific components of neighborhood environment would be beneficial in preventing excess weight in children.
Integrated silicon photonics works in the near‐infrared with bandwidth limited to the number of channels that can physically fit within a given chip. In article number 2004305, Joshua D. Caldwell and ...co‐workers report a hybrid heterostructure system composed of a hexagonal boron nitride (hBN) slab on top of a silicon waveguide to realize multiplexing of both near‐ and mid‐infrared signals. The sub‐diffractional hyperbolic polaritons supported in hBN are guided by the underlying silicon structure, propagating with, but not influencing, the near‐IR signal.
Platelets play a fundamental role in hemostasis and thrombosis. They are also involved in pathologic conditions resulting from blocked blood vessels, including myocardial infarction and ischemic ...stroke. Platelet adhesion, activation, and aggregation at sites of vascular injury are regulated by a diverse repertoire of tyrosine kinase–linked and G protein–coupled receptors. Src family kinases (SFKs) play a central role in initiating and propagating signaling from several platelet surface receptors; however, the underlying mechanism of how SFK activity is regulated in platelets remains unclear. CD148 is the only receptor-like protein tyrosine phosphatase identified in platelets to date. In the present study, we show that mutant mice lacking CD148 exhibited a bleeding tendency and defective arterial thrombosis. Basal SFK activity was found to be markedly reduced in CD148-deficient platelets, resulting in a global hyporesponsiveness to agonists that signal through SFKs, including collagen and fibrinogen. G protein–coupled receptor responses to thrombin and other agonists were also marginally reduced. These results highlight CD148 as a global regulator of platelet activation and a novel antithrombotic drug target.
The importance of emerging powers in the UN development system is undeniable, but their influence over the shape of the post-2015 agenda is less clear. This article examines recent survey data by the ...Future UN Development System (funds) Project in order to better gauge the perceptions of the world organisation's problems and prospects.
Prenatal fish intake is a key source of omega-3 (ω-3) polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum ...disorder (ASD) and related traits are lacking.
This study aimed to examine associations of prenatal fish intake and ω-3 supplement use with both autism diagnosis and broader autism-related traits.
Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and ω-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-second edition (n = 3939 and v3609 for fish intake analyses, respectively; n = 4537 and n = 3925 for supplement intake analyses, respectively).
In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (odds ratio: 0.84; 95% confidence interval CI: 0.77, 0.92), and a modest reduction in raw total SRS scores (β: −1.69; 95% CI: −3.3, −0.08). Estimates were similar across categories of fish consumption from “any” or “less than once per week” to “more than twice per week.” For ω-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (β: 1.98; 95% CI: 0.33, 3.64).
These results extend previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.
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