Annals of the New York Academy of Sciences最新文献

Metabolic dysfunction−associated liver disease (MASLD) and steatohepatitis (MASH) are becoming the most common causes of chronic liver disease in the United States and worldwide due to the obesity and diabetes epidemics. It is estimated that by 2030 close to 100 million people might be affected and patients with type 2 diabetes are especially at high risk. Twenty to 30% of patients with MASLD can progress to MASH, which is characterized by steatosis, necroinflammation, hepatocyte ballooning, and in advanced cases, fibrosis progressing to cirrhosis. Clinically, it is recognized that disease progression in diabetic patients is accelerated and the role of various genetic and epigenetic factors, as well as cell–matrix interactions in fibrosis and stromal remodeling, have recently been recognized. While there has been great progress in drug development and clinical trials for MASLD/MASH, the complexity of these pathways highlights the need to improve diagnosis/early detection and develop more successful antifibrotic therapies that not only prevent but reverse fibrosis.

To reduce micronutrient deficiencies, Senegal mandates the fortification of refined oil with vitamin A and wheat flour with iron and folic acid. Expanding Senegal's large-scale food fortification programs to include fortified bouillon could help fill the remaining gaps in dietary micronutrient requirements. Using 7-day household food consumption data collected between 2018 and 2019, we assessed the potential contributions of bouillon fortified with vitamin A (40–250 μg/g bouillon), folic acid (20–120 μg/g), vitamin B12 (0.2–2 μg/g), iron (0.6–5 mg/g), and zinc (0.6–5 mg/g) for meeting micronutrient requirements of women of reproductive age (WRA; 15–49 years old) and children (6–59 months old). Most households (90%) reported consuming bouillon, including poor and rural households. At modeled fortification levels, bouillon fortification reduced the national prevalence of inadequacy by up to ∼20 percentage points (pp) for vitamin A, 34 pp (WRA) and 20 pp (children) for folate, 20 pp for vitamin B12, 38 pp (WRA) and 30 pp (children) for zinc, and ∼8 pp for iron. Predicted reductions in inadequacy were generally larger among poor and rural populations, especially for vitamins A and B12. Our modeling suggests that bouillon fortification has the potential to substantially reduce dietary inadequacy of multiple micronutrients and could also help address inequities in dietary micronutrient inadequacies in Senegal.

Goldenhar syndrome, a rare craniofacial malformation, is characterized by developmental anomalies in the first and second pharyngeal arches. Its etiology is considered to be heterogenous, including both genetic and environmental factors that remain largely unknown. To further elucidate the genetic cause in a five-generation Goldenhar syndrome pedigree and exploit the whole-exome sequencing (WES) data of this pedigree, we generated collapsed haplotype pattern markers based on WES and employed rare variant nonparametric linkage analysis. FBLN2 was identified as a candidate gene via analysis of WES data across the significant linkage region. A fbln2 knockout zebrafish line was established by CRISPR/Cas9 to examine the gene's role in craniofacial cartilage development. fbln2 was expressed specifically in the mandible during the zebrafish early development, while fbln2 knockout zebrafish exhibited craniofacial malformations with abnormal chondrocyte morphologies. Functional studies revealed that fbln2 knockout caused abnormal chondrogenic differentiation, apoptosis, and proliferation of cranial neural crest cells (CNCCs), and downregulated the bone morphogenic protein (BMP) signaling pathway in the zebrafish model. This study demonstrates the role of FBLN2 in CNCC development and BMP pathway regulation, and highlights FBLN2 as a candidate gene for Goldenhar syndrome, which may have implications for the selection of potential screening targets and the development of treatments for conditions like microtia-atresia.

This study explores the impact of feathers on the hydrodynamic drag experienced by diving birds, which is critical to their foraging efficiency and survival. Employing a novel experimental approach, we analyzed the kinematics of both feathered and nonfeathered projectiles during their transition from air to water using high-speed imaging and an onboard accelerometer. The drag coefficients were determined through two methods: a direct calculation from the acceleration data and a theoretical approach fitted to the observed velocity profiles. Our results indicate that feathers significantly increase the drag force during water entry, with feathered projectiles exhibiting approximately double the drag coefficient of their smooth counterparts. These findings provide new insights into the role of avian feather morphology in diving mechanics and have potential implications for the design of bioinspired aquatic vehicles in engineering. The study also discusses the biological implications of increased drag due to feathers and suggests that factors such as body shape might play a more critical role in the diving capabilities of birds than previously understood.

One difference among writing systems is how orthographic cues are used to demarcate words; although most alphabetic scripts use inter-word spaces, some Asian scripts do not explicitly mark word boundaries (e.g., Chinese). It is unclear whether these differences are arbitrary or whether they are designed to maximize reading efficiency. Here, we show that spaces inserted between words in non-demarcated scripts provide less information about word boundaries than spaces in demarcated scripts. Furthermore, despite the fact that less information is contained by inter-word spaces than characters/letters of the same size, the information content of inter-word spaces in demarcated scripts is closer to that of characters/letters compared to the information content of inter-word spaces that are inserted in non-demarcated scripts. These results suggest that the conventions used to demarcate word boundaries are sufficient to support efficient reading. Our findings provide new insights into the universals and variation across writing systems and shed light on the mental processes that support skilled reading.

Interdisciplinary investigations of the human mind through the cognitive sciences have identified a key role of the body in representing knowledge. After characterizing knowledge at grounded, embodied, and situated levels, number knowledge is analyzed from this hierarchical perspective. Lateralized cortical processing of coarse versus fine detail is identified as a grounding substrate for the population stereotype few/left, many/right, which then contributes to number-related sensory and motor biases at the embodied and situated levels. Implications of this perspective for education and rehabilitation are discussed.

Considerable debate exists about the interplay between auditory and motor speech systems. Some argue for common neural mechanisms, whereas others assert that there are few shared resources. In four experiments, we tested the hypothesis that priming the speech motor system by repeating syllable pairs aloud improves subsequent syllable discrimination in noise compared with a priming discrimination task involving same–different judgments via button presses. Our results consistently showed that participants who engaged in syllable repetition performed better in syllable discrimination in noise than those who engaged in the priming discrimination task. This gain in accuracy was observed for primed and new syllable pairs, highlighting increased sensitivity to phonological details. The benefits were comparable whether the priming tasks involved auditory or visual presentation. Inserting a 1-h delay between the priming tasks and the syllable-in-noise task, the benefits persisted but were confined to primed syllable pairs. Finally, we demonstrated the effectiveness of this approach in older adults. Our findings substantiate the existence of a speech production–perception relationship. They also have clinical relevance as they raise the possibility of production-based interventions to improve speech perception ability. This would be particularly relevant for older adults who often encounter difficulties in perceiving speech in noise.

Micronutrient interventions can reduce child mortality. By applying Micronutrient Intervention Modeling methods in Senegal, Burkina Faso, and Nigeria, we estimated the impacts of bouillon fortification on apparent dietary adequacy of vitamin A and zinc among children and folate among women. We then used the Lives Saved Tool to predict the impacts of bouillon fortification with ranges of vitamin A, zinc, and folic acid concentrations on lives saved among children 6–59 months of age. Fortification at 250 µg vitamin A/g and 120 µg folic acid/g was predicted to substantially reduce vitamin A– and folate-attributable deaths: 65% for vitamin A and 92% for folate (Senegal), 36% for vitamin A and 74% for folate (Burkina Faso), and >95% for both (Nigeria). Zinc fortification at 5 mg/g would avert 48% (Senegal), 31% (Burkina Faso), and 63% (Nigeria) of zinc-attributable deaths. The addition of all three nutrients at 30% of Codex nutrient reference values in 2.5 g bouillon was predicted to save an annual average of 293 child lives in Senegal (3.5% of deaths from all causes among children 6–59 months of age), 933 (2.1%) in Burkina Faso, and 18,362 (3.7%) in Nigeria. These results, along with evidence on program feasibility and costs, can help inform fortification program design discussions.

This chapter of the New York City Panel on Climate Change 4 (NPCC4) report discusses the many intersecting social, ecological, and technological-infrastructure dimensions of New York City (NYC) and their interactions that are critical to address in order to transition to and secure a climate-adapted future for all New Yorkers. The authors provide an assessment of current approaches to “future visioning and scenarios” across community and city-level initiatives and examine diverse dimensions of the NYC urban system to reduce risk and vulnerability and enable a future-adapted NYC. Methods for the integration of community and stakeholder ideas about what would make NYC thrive with scientific and technical information on the possibilities presented by different policies and actions are discussed. This chapter synthesizes the state of knowledge on how different communities of scholarship or practice envision futures and provides brief descriptions of the social-demographic and housing, transportation, energy, nature-based, and health futures and many other subsystems of the complex system of NYC that will all interact to determine NYC futures.

This chapter of the New York City Panel on Climate Change 4 (NPCC4) report considers climate health risks, vulnerabilities, and resilience strategies in New York City's unique urban context. It updates evidence since the last health assessment in 2015 as part of NPCC2 and addresses climate health risks and vulnerabilities that have emerged as especially salient to NYC since 2015. Climate health risks from heat and flooding are emphasized. In addition, other climate-sensitive exposures harmful to human health are considered, including outdoor and indoor air pollution, including aeroallergens; insect vectors of human illness; waterborne infectious and chemical contaminants; and compounding of climate health risks with other public health emergencies, such as the COVID-19 pandemic. Evidence-informed strategies for reducing future climate risks to health are considered.