Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals

Integrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage genomic diversity for discovery. In addition, these analyses have principally involved known metabolites, with the majority of the profiled peaks left unannotated. Here, we perform a whole genome association study of 2,291 metabolite peaks (known and unknown features) in 2,466 Black individuals from the Jackson Heart Study. We identify 519 locus-metabolite associations for 427 metabolite peaks and validate our findings in two multi-ethnic cohorts. A significant proportion of these associations are in ancestry specific alleles including findings in APOE, TTR and CD36. We leverage tandem mass spectrometry to annotate unknown metabolites, providing new insight into hereditary diseases including transthyretin amyloidosis and sickle cell disease. Our integrative omics approach leverages genomic diversity to provide novel insights into diverse cardiometabolic diseases

Proteomic Profiling Platforms Head to Head: Leveraging Genetics and Clinical Traits to Compare Aptamer- And Antibody-Based Methods

High-throughput proteomic profiling using antibody or aptamer-based affinity reagents is used increasingly in human studies. However, direct analyses to address the relative strengths and weaknesses of these platforms are lacking. We assessed findings from the SomaScan1.3K (N = 1301 reagents), the SomaScan5K platform (N = 4979 reagents), and the Olink Explore (N = 1472 reagents) profiling techniques in 568 adults from the Jackson Heart Study and 219 participants in the HERITAGE Family Study across four performance domains: precision, accuracy, analytic breadth, and phenotypic associations leveraging detailed clinical phenotyping and genetic data. Across these studies, we show evidence supporting more reliable protein target specificity and a higher number of phenotypic associations for the Olink platform, while the Soma platforms benefit from greater measurement precision and analytic breadth across the proteome

Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program

Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.e., lifestyle [ILS], metformin [MET], or placebo [PLA]), over an average of 3.2 years of follow-up. We found 69 metabolites associated with incident T2D regardless of treatment randomization. In particular, cytosine was novel and associated with the lowest risk. In an exploratory analysis, 35 baseline metabolite associations with incident T2D differed across the treatment groups. Stratification by baseline levels of several of these metabolites, including specific phospholipids and AMP, modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventative treatment effect in individuals who are clinically at high risk and motivate further studies to validate these interactions

Protein-metabolite association studies identify novel proteomic determinants of metabolite levels in human plasma

Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma samples from three human cohorts. We detected 171,800 significant protein-metabolite pairwise correlations between 1,265 proteins and 365 metabolites, including established relationships in metabolic and signaling pathways such as the protein thyroxine-binding globulin and the metabolite thyroxine, as well as thousands of new findings. In Mendelian randomization (MR) analyses, we identified putative causal protein-to-metabolite associations. We experimentally validated top MR associations in proof-of-concept plasma metabolomics studies in three murine knockout strains of key protein regulators. These analyses identified previously unrecognized associations between bioactive proteins and metabolites in human plasma. We provide publicly available data to be leveraged for studies in human metabolism and disease

Investigate of Bitter Component in Bamboo Shoot

In the present study, the objective was to investigate the relationship between bitter components and whether the bamboo shoots greening or not within Dendrocalamus hamiltonii Nees et Arn. ex Munro which is known for no bitterness taste and other verities of bamboo shoots. Taxiphyllin can be decomposed to hydrogen cyanide and p-hydroxybenzaldehyde. Hydrogen cyanide concentrations are high in the top of bamboo shoots, and get lower in the base of bamboo shoots. In greening bamboo shoots of Leleba oldhami Nakai, hydrogen cyanide concentrations are 3.12 mg/g•F.W in the top, 2.87 mg/g•F.W. in the middle, and 0.48 mg/g•F.W. in the base. But in etiolated bamboo shoots of Leleba oldhami Nakai, hydrogen cyanide concentrations are 0.44 mg/g•F.W in the top, 0.03 mg/g•F.W. in the middle, and 0.00 mg/g•F.W. in the base. Hydrogen cyanide concentrations have significant differences between greening bamoo shoots and etiolated shoots of Leleba oldhami Nakai. There are similar results in other verities. Like Dendrocalamus latifloxus Munro, and Leleba edulis Odashimo. However, there are very low hydrogen cyanide concentrations in Dendrocalamus hamiltonii Nees et Arn. ex Munro. The sensory evaluation, shows positive correlations between bitterness and accumulation of hydrogen cyanide. Besides, total phenolic compounds, free amino acids, and soluble proteins in Dendrocalamus hamiltonii Nees et Arn. ex Munro are lower than Leleba oldhami Nakai.本試驗擬調查筍出青與否之苦味物質變化，與不具苦味之甜龍筍進行比較，以確定甜龍筍無論出青與否均不具苦味的原因。紫杉氰醣苷分解後產物為氰酸 (HCN) 與對羥基苯乙醇腈 (p-Hydroxybenzaldehyde)，藉由測定氰酸含量，可得知紫杉氰醣苷的累積程度。竹筍氰酸濃度頂端最高，往下而遞減。出青綠竹筍氰酸濃度頂段 3.12 mg/g•F.W.、中段 2.87 mg/g•F.W.、底段 0.48 mg/g•F.W.；未出青綠竹筍氰酸濃度依序為 0.44、0.03、0.00 mg/g•F.W.。顯示綠竹筍出青與否對氰酸濃度有明顯之差異，而麻竹筍、烏殼綠竹筍、也有相同趨勢。然而甜龍筍無論出青與否，在各部位氰酸累積均極低，在官能品評上，亦沒有苦味之口感，顯示苦味產生與氰酸之累積具有相關性。此外，總酚類化合物、總游離胺基酸、及可溶性性蛋白質甜龍筍較綠竹筍低。中文摘要 ii Summary iii 壹、前言 1 貳、前人研究 2 一、竹筍概述 2 二、食用竹筍苦味 3 三、竹筍營養價值 4 參、材料與方法 5 一、 材料 5 (一) 第一次試驗 5 (二) 第二次試驗 5 二、 竹筍外觀與色澤 5 三、 出青與未出青竹筍之品質分析 6 (一) 多酚氧化酶活性、過氧化酶活性及氰酸 6 (二) 總酚類化合物、游離胺基酸、可溶性蛋白質及酪胺酸 6 (三) 總可溶性固形物 7 四、 煮沸處理對竹筍品質之影響 8 (一) 官能品評 8 五、 統計分析 8 肆、試驗結果 10 一、竹筍不同部位與出青與否氰酸含量差異 10 二、夏季常見食用筍出青與否之官能品評與品質調查 14 伍、討論 20 一、食用筍出青與否之官能品評與不同部位與出青與否氰酸含量差異 20 二、夏季常見食用筍品質調查 21 參考文獻 22 附錄 2

Massive Thymic Hyperplasia Masquerading as Cancer: A Case Report and Review of the Literature

A 34-year-old woman presenting with abdominal pain, chest pressure, weight loss, and tachycardia was found to have an 11.4-cm anterior mediastinal mass associated with intrathoracic lymphadenopathy on chest computed tomography (Fig. 1A). Core needle biopsy was concerning for a type B1 thymoma.During this patient’s initial workup, she was found to have both clinical and laboratory evidence of Graves’ thyroiditis, raising diagnostic suspicion for thymic hyperplasia rather than thymoma. The case discussed here highlights the unique challenges that arise in the evaluation and management of thymic masses and serves as a prudent reminder that both benign and malignant disorders may present with mass-like changes

A parametric bootstrap approach for computing confidence intervals for genetic correlations with application to genetically determined protein-protein networks

Summary: Genetic correlation refers to the correlation between genetic determinants of a pair of traits. When using individual-level data, it is typically estimated based on a bivariate model specification where the correlation between the two variables is identifiable and can be estimated from a covariance model that incorporates the genetic relationship between individuals, e.g., using a pre-specified kinship matrix. Inference relying on asymptotic normality of the genetic correlation parameter estimates may be inaccurate when the sample size is low, when the genetic correlation is close to the boundary of the parameter space, and when the heritability of at least one of the traits is low. We address this problem by developing a parametric bootstrap procedure to construct confidence intervals for genetic correlation estimates. The procedure simulates paired traits under a range of heritability and genetic correlation parameters, and it uses the population structure encapsulated by the kinship matrix. Heritabilities and genetic correlations are estimated using the close-form, method of moment, Haseman-Elston regression estimators. The proposed parametric bootstrap procedure is especially useful when genetic correlations are computed on pairs of thousands of traits measured on the same exact set of individuals. We demonstrate the parametric bootstrap approach on a proteomics dataset from the Jackson Heart Study

RESPUESTA DE TRES VARIEDADES DE ARROZ (ORYZA SATIVA) A DIFERENTES NIVELES DE NITR6GENO EN LA LINEA NOROESTE DE LA REPUBLICA DOMINICANA

Durante la etapa de primavera-verano de afio 1999, el Centro de Investigaciones Arroceras (CEDIA) localizado en Juma, Bonao, Republica Dominicana, realizo el presente experimento en la zona de Esperanza, Mao-Valverde, con el objetivo de determinar la respuesta de las variedades de arroz Juma 66, Juma 67 e ISA -40. En la que fue utilizado un diseflo en bloques al azar, con cuatros repeticiones, trasplantada a un marco de siembra de 0.25 x 0.25 m con 5 plantas por golpes, en parcelas experimentales de 10 m2 . Los tratamientos en estudio correspondieron a 8 niveles de nitrdgeno (0,25,50,75,100,125, 150 y 175kg.ha-l). Los resultados obtenidos muestran que, los rendimientos en grano aumentaran, con el aumento de los niveles de nitrdgeno aplicado, en las diferentes variedades. La variedad Juma 66 reporto el mas alto rendimiento en comparacion con las demas variedades, llegando a alcanzar un rendimiento grano de 6514 kg.ha-1, teniendo esta variedad una respuesta al nitrdgeno aplicado representada por la ecuacion de segundo grado Y = 3324 + 30.276X - 0.0721X2 y un coeficiente de determination igual a R2 =0.97 , igual comportamiento registro la variedad Isa-40 con una ecuacion de Y = 3132.6 + 28.733X - 0.0944X2 y R2=0.94, mientras que la variedad Juma 67 presento un aumento linear de los rendimientos por efecto de la aplicacion de nitrdgeno con la ecuacion Y = 3039.2 + 19.027X con R2=0.98, indicando que la variedad Juma 66 presenta un efecto mayor sobre los rendimiento por cada kg. de nitrdgeno aplicado. La altura promedio alcanzada fuede 93.4,84.1 y 83.0 cm, para las variedades Juma 66, Isa-40 y Juma 67 respectivamente

Conservation of the Eastern Taiwan Strait Chinese White Dolphin (Sousa chinensis): Fishers' Perspectives and Management Implications.

The abundance of the eastern Taiwan Strait (ETS) population of the Chinese white dolphin (Sousa chinensis) has been estimated to be less than 100 individuals. It is categorized as critically endangered in the IUCN Red List of Threatened Species. Thus, immediate measures of conservation should be taken to protect it from extinction. Currently, the Taiwanese government plans to designate its habitat as a Major Wildlife Habitat (MWH), a type of marine protected area (MPA) for conservation of wildlife species. Although the designation allows continuing the current exploitation, however, it may cause conflicts among multiple stakeholders with competing interests. The study is to explore the attitude and opinions among the stakeholders in order to better manage the MPA. This study employs a semi-structured interview and a questionnaire survey of local fishers. Results from interviews indicated that the subsistence of fishers remains a major problem. It was found that stakeholders have different perceptions of the fishers' attitude towards conservation and also thought that the fishery-related law enforcement could be difficult. Quantitative survey showed that fishers are generally positive towards the conservation of the Chinese white dolphin but are less willing to participate in the planning process. Most fishers considered temporary fishing closure as feasible for conservation. The results of this study provide recommendations for future efforts towards the goal of better conservation for this endangered species