Biology subjects

Jones, N. P.

Publications and source records attributed to Jones, N. P..

4 recordsLinked to original sources

bioRxiv2025

Basal Ganglia Dopamine Availability and Immune Activation Interact and Relate to Anhedonia Severity among Youth with Depression

Anhedonia emerges in adolescence, has putative substrates in neural reward and dopamine systems, and is a hallmark of poor course in depression. Psychoneuroimmunology models suggest altered immune and reward systems may jointly underlie its development. When dopamine availability (rather than function) is considered, immune activation may be understood as a moderator amplifying how lower dopamine levels translate into motivational deficits. This cross-sectional study analyzed data from 55 youth with current depression (Mage=21.4 years; Female=75%). Plasma was assayed for relative quantification of 92 immune proteins, followed by dimensionality reduction via principal component (PC) analysis, forming five PC scores. Dopamine availability was indexed by basal ganglia tissue iron, quantified by MRI R2, a measure detectable in youth. Anhedonia was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS), thought to capture overall anhedonia, and Positive Valence Systems Scale (PVSS), which provides overall, anticipatory, and consummatory anhedonia scores. PC1 scores--whose loadings indicated broadly distributed immune protein elevations consistent with general immune activation--moderated the relationship between basal ganglia dopamine availability and anhedonia: At higher PC1 levels, lower dopamine availability was linked to greater overall anhedonia (as measured by SHAPS) and anticipatory anhedonia, but not to consummatory anhedonia. Lower PC2 scores were associated with greater PVSS overall and consummatory anhedonia. Analyses examining individual basal ganglia regions suggest potential differences in dopaminergic-immune interactions across these regions, with effects most consistently observed in the putamen. Findings highlight nuanced neuroimmune pathways underlying anhedonia components in youth and support inflammation-based models of depression emphasizing dopaminergic-immune interplay.

neuroscience↗

bioRxiv2025

Environmental conditions modulate constitutive and induced host immunity contributing to spatial patterns of coral disease susceptibility

Disease outbreaks have caused mass mortality and threaten the persistence of numerous vulnerable species, including reef-building corals. Spatiotemporal variations in disease prevalence suggest environmental conditions exacerbate disease susceptibility, potentially by compromising host immunity. Understanding how these variations influence disease dynamics and immunity may enable improved prediction of future disease outbreaks. We combined field observations and statistical modeling to identify the environmental drivers of stony coral tissue loss disease (SCTLD) in Florida. We then performed environmental manipulation experiments to confirm the effects of identified factors on immunity in the massive coral Montastraea cavernosa. SCTLD susceptibility was influenced most by the interaction between temperature and chlorophyll-a concentration (nutrients proxy) the month prior to disease survey, as well as the interaction between chlorophyll-a and three-month mean PAR. SCTLD prevalence was highest when temperatures were low (<30 {degrees}C) and chlorophyll-a concentration exceeded [~]6 mg m-3 and/or when PAR and chlorophyll-a concentrations were high. SCTLD severity had a negative relationship with temperature, a colony had a higher probability of dying during the SCTLD outbreak when temperatures stayed below 31.08 {degrees}C, a finding in contrast to previous coral disease studies. In the laboratory, coral fragments were exposed to temperature and nutrient manipulation, then immune challenged. Heat stress largely drove suppression of baseline immunity but increased production of some antioxidants, suggesting host stress. Fragments exposed to moderate ammonium concentration induced the strongest immune responses compared to those grown under high or no ammonium conditions. Combined with modeling results, these findings support long-standing hypotheses that coral disease susceptibility is at least, in part, modulated by environmentally induced changes in immunity. Overall, our results enhance the understanding of the impact of environmental conditions on SCTLD outbreaks and on general coral immunity. They also highlight the possibility of increased disease severity as anthropogenic pressure on marine environments increases.

ecology↗

bioRxiv2020

The deubiquitylase USP9X controls ribosomal stalling

When a ribosome stalls during translation, it runs the risk of collision with a trailing ribosome. Such an encounter leads to the formation of a stable di-ribosome complex, which needs to be resolved by a dedicated machinery. The initial stalling and the subsequent resolution of di-ribosomal complexes requires activity of Makorin and ZNF598 ubiquitin E3 ligases respectively, through ubiquitylation of the eS10 and uS10 sub-units of the ribosome. It is common for the stability of RING E3 ligases to be regulated by an interacting deubiquitylase (DUB), which often opposes auto-ubiquitylation of the E3. Here, we show that the DUB USP9X directly interacts with ZNF598 and regulates its abundance through the control of protein stability in human cells. We have developed a highly specific small molecule inhibitor of USP9X. Proteomics analysis, following inhibitor treatment of HCT116 cells, confirms previous reports linking USP9X with centrosome associated protein stability and reveals loss of ZNF598 and Makorin 2. In the absence of USP9X or following chemical inhibition of its catalytic activity, steady state levels of Makorins and ZNF598 are diminished and the ribosomal quality control pathway is impaired.

cell biology↗

bioRxiv2020

Identifying strategies to target the metabolic flexibility of tumours.

Plasticity of cancer metabolism can be a major obstacle for efficient targeting of tumour-specific metabolic vulnerabilities. Here, we identify and quantify the compensatory mechanisms following the inhibition of major pathways of central carbon metabolism in c-MYC-induced liver tumours. We find that glutaminase isoform Gls2, expressed in normal liver, compensates for the deletion of Gls1 isoform expressed in tumours. Inhibiting both glutaminases significantly delays tumourigenesis but does not completely block glutamine catabolism through the Krebs cycle. We reveal that glutamine catabolism is then driven by amidotransferases. Consistently, the synergistic effect of glutaminase and amidotransferase inhibitors on proliferation of mouse and human tumour cells is observed in vitro and in vivo. Furthermore, when Gls1 is deleted the Krebs cycle activity and tumour formation can also be significantly affected if glycolysis is co-inhibited (Gls1KO/Hk2KO). Finally, the inhibition of either serine (Psat1KO) or fatty acid (FasnKO) biosynthesis can be compensated by uptake of circulating nutrients. Thus, removing these nutrients from the diet produces synergistic effects on suppression of tumourigenesis. These results highlight the high flexibility of tumour metabolism and demonstrate how targeting compensatory mechanisms can improve a therapeutic outcome.

cancer biology↗