Biology subjects

Long, N.

Publications and source records attributed to Long, N..

6 recordsLinked to original sources

bioRxiv2025

A Rapid Gene Expression Profiler Classifies AML Tumor Responsiveness to Standard Therapies

The emergence of transcriptional signatures that define cell types and pathways has made it possible to guide cancer therapy selection through gene expression profiling. We developed a rapid qPCR-based platform to profile cell state, stemness, and BCL2 family gene expression as a companion diagnostic test for acute myeloid leukemia (AML). We validated the stability and utility of the signatures across multiple measurement platforms and using patient samples from two centers. Integrating these signatures with clinical features enables an expedient means to predict the likelihood of patient responses to two standard-of-care therapies: intensive chemotherapy and hypomethylating agent plus venetoclax (HMA+Ven). For patients treated with HMA+Ven, expression levels of the promonocyte-like signature and BCL2 add predictive value for response and overall survival in multivariable models that include genetic features. The incorporation of the rapid profiler into the prospective evaluation of newly diagnosed AML patients may enhance treatment stratification and improve outcomes.

cancer biology↗

bioRxiv2025

A New Type of Nonsuppressible Viremia Produced by HIV-Infected Macrophage

BackgroundHIV-1 RNA typically declines rapidly after initiation of antiretroviral therapy (ART); often reaching undetectable levels within a few weeks and remaining undetectable by standard assays. However, some patients on ART have persistent nonsuppressible viremia (NSV) that does not respond to treatment optimization or intensification. NSV can emerge at the time of ART initiation (primary NSV) or after being ART-suppressed (secondary NSV). Here, we examine mechanisms producing primary NSV in four people on ART. MethodsBlood samples were collected from four participants who, despite being adherent to ART, required approximately a year or more to become virologically suppressed. Viral RNA and proviral DNA genomes were sequenced to examine HIV-1 drug resistance, genome intactness and genetic diversity. The ability of HIV-1 Envs to facilitate efficient entry into cells expressing low levels of CD4 (a proxy for macrophage tropism) was assessed. ResultsBefore ART, the blood contained HIV-1 RNA genomes that were adapted to replication in CD4+ T cells and rapidly decayed after ART initiation. During ART, the blood contained HIV-1 genomes that were drug sensitive, genetically diverse, macrophage-tropic, not evolving and often had defects in vpr. ConclusionsOur results suggest that in individuals with primary NSV, ART stopped virus replication, but large pools of long-lived, HIV-infected macrophage continued to produce virus. This is mechanistically distinct from secondary NSV produced by CD4+ T cell clones. In addition, defects in vpr independently accumulation in macrophage-tropic lineages found in three participants, suggesting that vpr may impact survival of, or virus production from, HIV-infected macrophage. SUMMARYPeople with HIV-1 on ART can experience persistent, nonsuppressible viremia (NSV). We identified four people with a previously uncharacterized form of NSV that emerged at the time of ART initiation (primary NSV) and is notable for its genetic diversity, drug sensitivity, and macrophage tropism. This is mechanistically distinct from previously described cases of NSV produced by CD4+ T cells in people who were previously ART-suppressed (secondary NSV).

microbiology↗

bioRxiv2022

Nucleotide resolution genetic mapping in pigs by publicly accessible whole genome imputation

Genetic mapping to identify genes and alleles associated with or causing economically important quantitative trait variation in livestock animals such as pigs is a major goal in the genetic improvement animals. Despite recent advances in high throughput genotyping technologies, resolution of genetic mapping in pigs remains poor due in part to the low density of genotyped variant sites. In this study, we overcame this limitation by developing a reference haplotype panel for pigs based on 2,259 whole genome sequenced animals representing 44 pig breeds. We optimized the imputation procedure to achieve an average concordance rate in excess of 97%, non-reference concordance rate 91%, and r2 0.89. We demonstrated that genotype imputation using this resource can dramatically improve resolution of genetic mapping. Finally, we developed a public web server (swimgeno.org) to allow the pig genetics community to fully utilize this resource. We expect the resource and server to significantly facilitate genetic mapping and accelerate genetic improvement in pigs.

genomics↗

bioRxiv2022

Dual Targeting of FLT3 and LSD1 Disrupts the MYC Super-Enhancer Complex in Acute Myeloid Leukemia

Mutations in Fms-like tyrosine kinase 3 (FLT3) are common drivers in acute myeloid leukemia (AML) yet FLT3 inhibitors only provide modest clinical benefit. Prior work has shown that inhibitors of lysine-specific demethylase 1 (LSD1) enhance kinase inhibitor activity in AML. Here we show that combined LSD1 and FLT3 inhibition induces synergistic cell death in FLT3-mutant AML. Multi-omic profiling revealed that the drug combination disrupts STAT5, LSD1, and GFI1 binding at the MYC blood super-enhancer, suppressing super-enhancer activation as well as MYC expression and activity. The drug combination simultaneously results in the accumulation of repressive H3K9me1 methylation, an LSD1 substrate, at MYC target genes. We validated these findings in 72 primary AML samples with the nearly every sample demonstrating synergistic responses to the drug combination. Collectively, these studies provide preclinical rationale for the investigation of dual FLT3/LSD1 inhibition in a clinical trial.

cancer biology↗

bioRxiv2019

Lipidomics analysis of juveniles blue mussels (Mytilus edulis L. 1758), a key economic and ecological species.

Blue mussels (Mytilus edulis L.) are important components of coastal ecosystems functioning through benthopelagic coupling and ecosystem engineering. At the same time, mussel production is central in the economy of coastal areas. Therefore, understanding their nutritional, physiological and metabolic processes at key life stages is important for their management, both within food production systems and in wild populations.\n\nLipids are crucial molecules for bivalve growth, but their diversity and roles have been considered from fatty acid (FA) perspective. In this paper, we applied lipidomics to bivalve nutrition. Lipidomics provides a holistic perspective on lipid patterns; by examining the lipidome, important physiological information can be acquired. Here, we use controlled laboratory experiments to elucidate the responses to changes in the diet of newly settled mussels juveniles, one of the most critical life stages. The diets considered in this study are single strains diet of Cylindrotheca fusiformis CCAP 1017/2 - CYL, Isochrysis galbana CCAP 927/1- ISO, Monodopsis subterranean CCAP 848/1 - MONO, Nannochloropsis oceanica CCAP 849/10- NANNO and a commercial algae paste -SP.\n\nThe diets had a significant effect on spat GR and WI, and according to their efficacy resulted ranked as follows: ISO>NANNO/CYL>SP>MONO. Spat FA composition and neutral lipid content (principally triacylglycerols - TG), were influenced by the diets. Furthermore, untargeted lipidomics also showed shifts in several phospholipid species, with changes related to the essential PUFA available from the diet. TG content, neutral lipids and several TG and FA species were correlated (Spearman R2>0.8 FDR p<0.05) with spat WI, suggesting their possible application as markers of mussel juvenile condition. The availability of dietary essential PUFA deeply modified the spat lipidome both for neutral and for polar lipids. This change in the lipidome could have major impacts on their ecology and their production for food.

biochemistry↗

bioRxiv2019

Influence of genetic interactions on polygenic prediction

Prediction of phenotypes from genotypes is an important objective to fulfill the promises of genomics, precision medicine and agriculture. Although its now possible to account for the majority of genetic variation through model fitting, prediction of phenotypes remains a challenge, especially across populations that have diverged in the past. In this study, we designed simulation experiments to specifically investigate the role of genetic interactions in failure of polygenic prediction. We found that non-additive genetic interactions can significantly reduce the accuracy of polygenic prediction. Our study demonstrated the importance of considering genetic interactions in genetic prediction.

genetics↗