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Acute myeloid leukemia (AML) is a devastating cancer affecting the hematopoietic system. Previous research has relied on RNA sequencing and microarray techniques to study the downstream effects of genomic alterations. While these studies have proven efficacious, they fail to capture the changes that occur at the proteomic level. To interrogate the effect of protein expression alterations in AML, we performed a quantitative mass spectrometry in parallel with RNAseq analysis using AML mouse models. These combined results identified 34 proteins whose expression was upregulated in AML tumors, but strikingly, were unaltered at the transcriptional level. Here we focus on mitochondrial electron transfer proteins ETFA and ETFB. Silencing of ETFA and ETFB led to increased mitochondrial activity, mitochondrial stress, and apoptosis in AML cells, but had little to no effect on normal human CD34+ cells. These studies identify a set of proteins that have not previously been associated with leukemia and may ultimately serve as potential targets for therapeutic manipulation to hinder AML progression and help contribute to our understanding of the disease.

Hematopoietic cell fate decisions such as self-renewal and differentiation are highly regulated through multiple molecular pathways. One pathway, the ubiquitin proteasome system (UPS), controls protein levels by tagging them with polyubiquitin chains and promoting their degradation through the proteasome. Ubiquitin E3 ligases serve as the substrate-recognition component of the UPS. By investigating the FBOX family of E3 ligases, we discovered that Fbxo21 was highly expressed in the hematopoietic stem and progenitor cell (HSPC) population, and exhibited low to no expression in mature myeloid populations. To determine the role of FBXO21 on HSPC maintenance, self-renewal, and differentiation, we generated shRNAs against FBXO21 and a hematopoiesis-specific Fbxo21 conditional knockout (cKO) mouse model. We found that silencing FBXO21 in HSPCs led to a loss in colony formation and an increase in cell differentiation in vitro. Additionally, stressing the HSPC populations in our Fbxo21 cKO mouse with 5-fluorouracil injections resulted in a decrease in survival, despite these populations exhibiting minimal alterations during steady-state hematopoiesis. Although FBXO21 has previously been proposed to regulate cytokine signaling via ASK and p38, our results indicate that depletion of FBXO21 led to altered ERK signaling in vitro. Together, these findings suggest ubiquitin E3 ligase FBXO21 regulates HSPCs through cytokine-mediated pathways.

Plant roots are shaping microbial communities that are distinct from the surrounding soil. These root-associated microbial communities can have both positive and negative effects on the host nutrient acquisition and thereby growth, yet how loss of soil microbial diversity will constrain the plant microbiome selection is relatively unknown. In this study, we manipulated the soil microbial community using a removal-by-dilution approach to examine how microbial diversity modulates microbiome selection in barley, including microbial guilds involved in nitrogen (N) cycling processes causing N loss, and its consequences for plant performance. We found that microbial diversity loss reduced the barley's ability to recruit specific microorganisms from the soil and only members of the Alphaproteobacteria and Bacteroidetes were enriched in both rhizosphere and root-associated compartments irrespective of dilution level. Loss in soil microbial diversity and the presence of plants affected the N-cycling communities, with the abundance of nitrous oxide reducers being 2–4 times higher in both barley compartments in the lower diversity soils. In these soils, the low abundance of bacterial ammonia oxidizers (close or below detection level in the barley compartments) was concomitant with an increase in leaf greenness (ca. 12%), an indicator of the plant N status. The reduction in soil microbial diversity was thus coupled to a change in functional traits of rhizosphere and root-associated communities, with consequences for plant performance. This work contributes to our understanding of plant-microbe interactions, which is needed to steer the crop microbiome towards increased N-use efficiency while minimizing negative environmental impact.

Acute myeloid leukemia (AML) is a devastating cancer affecting the hematopoietic system. Previous research has relied on RNA sequencing and microarray techniques to study the downstream effects of genomic alterations. While these studies have proven efficacious, they fail to capture the changes that occur at the proteomic level. To interrogate the effect of protein expression alterations in AML, we performed a quantitative mass spectrometry in parallel with RNAseq analysis using AML mouse models. These combined results identified 34 proteins whose expression was upregulated in AML tumors, but strikingly, were unaltered at the transcriptional level. Here we focus on mitochondrial electron transfer proteins ETFA and ETFB. Silencing of ETFA and ETFB led to increased mitochondrial activity, mitochondrial stress, and apoptosis in AML cells, but had little to no effect on normal human CD34

Nitrous oxide (N2O) is a potent greenhouse gas and its reduction to dinitrogen gas by the N2O reductase (encoded by the nosZ gene) is the only known biological N2O sink. Within the nosZ phylogeny there are two major clades (I and II), which seem to have different ecological niches. However, physiological differences of nosZI and nosZII expression that may impact emissions of N2O are not well understood. Here, we evaluated the differential expression of nosZI and nosZII, both present in Thauera linaloolentis strain 47LolT, in response to N2O concentration and the presence of the competing electron acceptor nitrate (NO3−). Different N2O levels had a negligible effect on the expression of both nosZ clades. Interestingly, nosZII expression was strongly upregulated in the absence of NO3−, while nosZI expression remained constant across the conditions tested. Thus, NO3− possibly inhibited nosZII expression, which suggests that N2O mitigation mediated by nosZII can be restricted due to the presence of NO3− in the environment. This is the first study demonstrating differential expression of nosZI and nosZII genes under the same physiological conditions and their implications for N2O emission under varying environmental conditions in terms of NO3− availability.