scholarly journals Transcriptomic, proteomic, and metabolomic analyses identify candidate pathways linking maternal cadmium exposure to altered neurodevelopment and behavior

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kathleen M. Hudson ◽  
Emily Shiver ◽  
Jianshi Yu ◽  
Sanya Mehta ◽  
Dereje D. Jima ◽  
...  

AbstractCadmium (Cd) is a ubiquitous toxic heavy metal of major public concern. Despite inefficient placental transfer, maternal Cd exposure impairs fetal growth and development. Increasing evidence from animal models and humans suggests maternal Cd exposure negatively impacts neurodevelopment; however, the underlying molecular mechanisms are unclear. To address this, we utilized multiple -omics approaches in a mouse model of maternal Cd exposure to identify pathways altered in the developing brain. Offspring maternally exposed to Cd presented with enlarged brains proportional to body weights at birth and altered behavior at adulthood. RNA-seq in newborn brains identified exposure-associated increases in Hox gene and myelin marker expression and suggested perturbed retinoic acid (RA) signaling. Proteomic analysis showed altered levels of proteins involved in cellular energy pathways, hypoxic response, and RA signaling. Consistent with transcriptomic and proteomic analyses, we identified increased levels of retinoids in maternally-exposed newborn brains. Metabolomic analyses identified metabolites with significantly altered abundance, supportive of changes to cellular energy pathways and hypoxia. Finally, maternal Cd exposure reduced mitochondrial DNA levels in newborn brains. The identification of multiple pathways perturbed in the developing brain provides a basis for future studies determining the mechanistic links between maternal Cd exposure and altered neurodevelopment and behavior.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kathleen M. Hudson ◽  
Scott M. Belcher ◽  
Michael Cowley

Abstract Cadmium (Cd) is a toxic heavy metal ubiquitous in the environment. Maternal exposure to Cd is associated with fetal growth restriction, trace element deficiencies, and congenital malformations. Cd exposure during adulthood is associated with cardiovascular disease (CVD); however, the effects of maternal Cd exposure on offspring cardiovascular development and disease are not well-understood. Utilizing a mouse model of maternal Cd exposure, we show that offspring born to Cd-exposed mothers have increased heart weights at birth and susceptibility to hypertension during adulthood. Despite inefficient maternal-fetal transfer of Cd, maternal Cd alters fetal levels of essential trace elements including a deficiency in iron, which is required for cardiovascular system development, oxygen homeostasis, and cellular metabolism. RNA-seq on newborn hearts identifies differentially expressed genes associated with maternal Cd exposure that are enriched for functions in CVD, hypertension, enlarged hearts, cellular energy, and hypoxic stress. We propose that a maternal Cd exposure-induced iron deficiency leads to altered cellular metabolic pathways and hypoxic conditions during fetal development; this stress may contribute to increased heart weight at birth and the programming of susceptibility to hypertension in adulthood. These studies will give insights into potential mechanisms through which maternal Cd exposure impacts cardiovascular development and disease.


2021 ◽  
Author(s):  
Zuyun Zhang ◽  
Zhen Li ◽  
Qiang Huang ◽  
Zhijiang Zeng

Abstract Exposure to insecticides is the main cause of honeybee (Apis mellifera) population decline. At sub-lethal doses, these chemicals have been shown to negatively affect honeybee physiological development and behavior. Previously, we found the insecticide imidacloprid and deltamethrin significant reduced honeybee dancing and foraging efficiency. As a follow up, we performed a deep RNA-seq analysis to reveal the gene regulatory mechanisms underlying the altered foraging behavior. Genes involved in detoxification were up-regulated in both imidacloprid and deltamethrin treatment groups. Gene members in immune pathways, odorant receptors and major royal jelly protein families showed significant up or down regulation in treatment groups compared with controls. This fluctuating gene expression profile reflects that multifaceted aspects of honeybee physiology were affected by the two insecticides, leading to inaccurate communication and impaired learning and memory. Our findings reveal candidate molecular mechanisms under impaired dance performance in honeybees exposed to insecticides.


2019 ◽  
Author(s):  
Scott A. Keith ◽  
Rory Eutsey ◽  
Heewook Lee ◽  
Brad Solomon ◽  
Stacie Oliver ◽  
...  

ABSTRACTSymbiotic microorganisms exert multifaceted impacts on the physiology of their animal hosts. Recent discoveries have shown the gut microbiota influence host brain function and behavior, but the host and microbial molecular factors required to actuate these effects are largely unknown. To uncover molecular mechanisms that underlie the gut-microbiota-brain axis, we used Drosophila melanogaster and its bacterial microbiota as a model to identify microbiota-dependent gene expression changes in the host brain and head. Specifically, we employed RNA-seq and nanoString nCounter technology to identify Drosophila genes that exhibit altered transcript levels in fly heads upon elimination of the microbiota. The identified genes, some of which exhibited sex-specific differences, have demonstrated or inferred functional roles in the immune response, metabolism, neuronal activity, and stress resistance. Overall, this study reveals microbiota-responsive genes in the fly head, an anatomical structure not previously investigated in this context. Our results serve as a foundation for future investigations of how microbe-driven gene expression changes impact Drosophila biology.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 241-242
Author(s):  
Yongjie Wang ◽  
Keshari Thakali ◽  
Sarah Shelby ◽  
Jason Apple ◽  
Yan Huang

Abstract The purpose of this study was to compare the meat quality and genomic differences between cross-bred commercial pig (CP) and domestic Large Black pig (BP). Seven cross-bred commercial pigs and eight British Large Black pigs were assigned to CP group and BP group, with initial mean body weights of 18.82±1.412 kg for CP group and 23.31±1.935 kg for BP group, P = 0.061, and fed ad libitum. The final BW of the CP at d101 was similar to the BP (130.0±8.16 kg vs. 121.1±2.80 kg, P = 0.132). However, the BP group took 108 days to reach the final BW. The ADG in the CP was higher than BP (1.102±0.0599 kg vs. 0.905±0.0138 kg, P = 0.003). The hot carcass weight of CP was higher (P < 0.01) than BP, but the backfat of BP was higher (P < 0.01) than CP. The a* value of CP was higher (P < 0.05) than BP, and the c* value of CP was tended to be higher (P < 0.10) than BP. However, the h value of BP was higher (P < 0.05) than CP. The longissimus dorsi muscle fat content of BP was higher (P < 0.05) than CP. For the fatty acid composition, the SFA and MUFA of BP were higher (P < 0.05) than CP, but the PUFA of CP was higher (P < 0.05) than BP. The metmyoglobin content of CP was tended to be higher (P < 0.10) than BP. For the meat metabolism, the oxygen consumption of longissimus dorsi muscle of BP was higher (P < 0.01) than CP. The RNA-Seq data showed that the expression of the genes related to lipid metabolism is higher in BP (fold change > 3, P < 0.05). To conclude, BP has higher meat quality, while CP has its advantages in growth performance. And the differences between these two breeds may due to the genomic diversity.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 896
Author(s):  
Yuenan Zhou ◽  
Pei Yang ◽  
Shuang Xie ◽  
Min Shi ◽  
Jianhua Huang ◽  
...  

The endoparasitic wasp Cotesia vestalis is an important biological agent for controlling the population of Plutella xylostella, a major pest of cruciferous crops worldwide. Though the genome of C. vestalis has recently been reported, molecular mechanisms associated with sexual development have not been comprehensively studied. Here, we combined PacBio Iso-Seq and Illumina RNA-Seq to perform genome-wide profiling of pharate adult and adult development of male and female C. vestalis. Taking advantage of Iso-Seq full-length reads, we identified 14,466 novel transcripts as well as 8770 lncRNAs, with many lncRNAs showing a sex- and stage-specific expression pattern. The differentially expressed gene (DEG) analyses showed 2125 stage-specific and 326 sex-specific expressed genes. We also found that 4819 genes showed 11,856 alternative splicing events through combining the Iso-Seq and RNA-Seq data. The results of comparative analyses showed that most genes were alternatively spliced across developmental stages, and alternative splicing (AS) events were more prevalent in females than in males. Furthermore, we identified six sex-determining genes in this parasitic wasp and verified their sex-specific alternative splicing profiles. Specifically, the characterization of feminizer and doublesex splicing between male and female implies a conserved regulation mechanism of sexual development in parasitic wasps.


Author(s):  
Guohong Zeng ◽  
Jin Li ◽  
Yuxiu Ma ◽  
Qian Pu ◽  
Tian Xiao ◽  
...  

AbstractSaponins are kinds of antifungal compounds produced by Panax notoginseng to resist invasion by pathogens. Ilyonectria mors-panacis G3B was the dominant pathogen inducing root rot of P. notoginseng, and the abilities to detoxify saponins were the key to infect P. notoginseng successfully. To research the molecular mechanisms of detoxifying saponins in I. mors-panacis G3B, we used high-throughput RNA-Seq to identify 557 and 1519 differential expression genes (DEGs) in I. mors-panacis G3B with saponins treatments for 4H (Hours) and 12H (Hours) compared with no saponins treatments, respectively. Among these DEGs, we found 93 genes which were simultaneously highly expressed in I. mors-panacis G3B with saponins treatments for 4H and 12H, they mainly belong to genes encoding transporters, glycoside hydrolases, oxidation–reduction enzymes, transcription factors and so on. In addition, there were 21 putative PHI (Pathogen–Host Interaction) genes out of those 93 up-regulated genes. In this report, we analyzed virulence-associated genes in I. mors-panacis G3B which may be related to detoxifying saponins to infect P. notoginseng successfully. They provided an excellent starting point for in-depth study on pathogenicity of I. mors-panacis G3B and developed appropriate root rot disease management strategies in the future.


2021 ◽  
Vol 22 (5) ◽  
pp. 2683
Author(s):  
Princess D. Rodriguez ◽  
Hana Paculova ◽  
Sophie Kogut ◽  
Jessica Heath ◽  
Hilde Schjerven ◽  
...  

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell acute lymphoblastic leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.


2021 ◽  
Vol 22 (13) ◽  
pp. 7029
Author(s):  
Cai-Yun Xiong ◽  
Qing-You Gong ◽  
Hu Pei ◽  
Chang-Jian Liao ◽  
Rui-Chun Yang ◽  
...  

In maize, the ear shank is a short branch that connects the ear to the stalk. The length of the ear shank mainly affects the transportation of photosynthetic products to the ear, and also influences the dehydration of the grain by adjusting the tightness of the husks. However, the molecular mechanisms of maize shank elongation have rarely been described. It has been reported that the maize ear shank length is a quantitative trait, but its genetic basis is still unclear. In this study, RNA-seq was performed to explore the transcriptional dynamics and determine the key genes involved in maize shank elongation at four different developmental stages. A total of 8145 differentially expressed genes (DEGs) were identified, including 729 transcription factors (TFs). Some important genes which participate in shank elongation were detected via function annotation and temporal expression pattern analyses, including genes related to signal transduction hormones (auxin, brassinosteroids, gibberellin, etc.), xyloglucan and xyloglucan xyloglucosyl transferase, and transcription factor families. The results provide insights into the genetic architecture of maize ear shanks and developing new varieties with ideal ear shank lengths, enabling adjustments for mechanized harvesting in the future.


Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Kijoon Kim ◽  
Melissa Melough ◽  
Terrence Vance ◽  
Hwayoung Noh ◽  
Sung Koo ◽  
...  

Cadmium (Cd) is a toxic heavy metal that can contribute to numerous diseases as well as increased mortality. Diet is the primary source of Cd exposure for most individuals, yet little is known about the foods and food groups that contribute most substantially to dietary Cd intake in the US. Therefore, the objective of this study was to estimate dietary Cd intake and identify major food sources of Cd in the US population and among subgroups of the population. Individuals aged 2 years and older from the National Health and Nutrition Examination Survey (NHANES) 2007–2012 were included in this study (n = 12,523). Cd intakes were estimated from two days of 24-h dietary recalls by matching intake data with the Cd database of the Food and Drug Administration (FDA)’s Total Diet Study 2006 through 2013. The average dietary Cd consumption in the population was 4.63 μg/day, or 0.54 μg/kg body weight/week, which is 22% of the tolerable weekly intake (TWI) of 2.5 μg/kg body weight/week. Greater daily Cd intakes were observed in older adults, males, those with higher income, higher education, or higher body mass index. The highest Cd intakes on a body weight basis were observed in children 10 years and younger (38% of TWI), underweight individuals (38% of TWI), and alcohol non-consumers (24% of TWI). The food groups that contributed most to Cd intake were cereals and bread (34%), leafy vegetables (20%), potatoes (11%), legumes and nuts (7%), and stem/root vegetables (6%). The foods that contributed most to total Cd intake were lettuce (14%), spaghetti (8%), bread (7%), and potatoes (6%). Lettuce was the major Cd source for Caucasians and Blacks, whereas tortillas were the top source for Hispanics, and rice was the top contributor among other ethnic subgroups including Asians. This study provides important information on the dietary Cd exposure of Americans, and identifies the groups with the greatest dietary Cd exposure as well as the major sources of dietary Cd among sociodemographic subgroups.


2015 ◽  
Vol 309 (10) ◽  
pp. F821-F834 ◽  
Author(s):  
Pinelopi P. Kapitsinou ◽  
Volker H. Haase

More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review.


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