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Parkin, a ring-between-ring-type E3 ubiquitin ligase, first shown to play a critical role in autosomal recessive juvenile Parkinsonism, has recently emerged as a key player in cancer biology. Parkin is now known to serve as a tumor suppressor, and its deregulation frequently promotes tumorigenesis. In this issue of the JCI , Perego et al. expand that role by showing that Parkin expression stimulated an interferon (IFN) response to modulate CD8 + T cell activity. These findings suggest that, in addition to directly inhibiting tumor progression, Parkin enhances antitumor immune responses, highlighting it as a promising therapeutic target for cancer treatment.

Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes to anti-tumor immunity, limiting tumor expansion. Mice lacking the ubiquitin ligase RNF5 exhibit attenuated activation of the unfolded protein response (UPR) components, which coincides with increased expression of inflammasome components, recruitment and activation of dendritic cells and reduced expression of antimicrobial peptides in intestinal epithelial cells. Reduced UPR expression is also seen in murine and human melanoma tumor specimens that responded to immune checkpoint therapy. Co-housing of Rnf5 −/− and WT mice abolishes the anti-tumor immunity and tumor inhibition phenotype, whereas transfer of 11 bacterial strains, including B. rodentium , enriched in Rnf5 −/− mice, establishes anti-tumor immunity and restricts melanoma growth in germ-free WT mice. Altered UPR signaling, exemplified in Rnf5 −/− mice, coincides with altered gut microbiota composition and anti-tumor immunity to control melanoma growth. RNF5 is a ubiquitin ligase regulating ER stress response. Here the authors show that Rnf5 deficiency potentiates immune response against melanoma via altered microbiota, and isolate bacterial strains that confer the same phenotype to wild type mice.

While Rwanda is aiming at environmental pollution resilience and green growth, some industries are still discharging untreated effluent into the environment. This study gives a general overview of the compliance level of industrial effluent discharge in Rwanda and the linked negative environmental impacts. It comprises qualitative and quantitative analyses of data obtained from wastewater samples collected from five selected industries in Rwanda. The selected industries had previously been audited and monitored by the Rwanda Environment Management Authority (REMA), due to complains from neighboring residents. The study found that the effluent discharge from wastewater treatment plants (WWTP) for all concerned industries failed to comply with (i) oil and grease (O&G) national and international tolerable parameter limits or the (ii) fecal coliforms national standard. In addition, a compliance level of 66.7% was observed for key water quality monitoring parameters (pH, dissolved oxygen (DO), biochemical oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS), and heavy metals (i.e., lead (Pb), cadmium (Cd), and chromium (Cr)). Following these study findings, one industry was closed by the REMA for deliberately discharging untreated effluent into an adjacent river. This study recommends the adoption of the best available technology for effluent treatment, installation or renovation of existing WWTPs, and the relocation to industrial zones of industries adjacent to fragile environments.

The protocol describes how to make transparent graphene neural electrodes for implantation onto the surface of the cerebral cortex in rodents and subsequent neural analysis by fluorescence microscopy, electrophysiology, optical coherence tomography, and optogenetics. Transparent graphene-based neural electrode arrays provide unique opportunities for simultaneous investigation of electrophysiology, various neural imaging modalities, and optogenetics. Graphene electrodes have previously demonstrated greater broad-wavelength transmittance (∼90%) than other transparent materials such as indium tin oxide (∼80%) and ultrathin metals (∼60%). This protocol describes how to fabricate and implant a graphene-based microelectrocorticography (μECoG) electrode array and subsequently use this alongside electrophysiology, fluorescence microscopy, optical coherence tomography (OCT), and optogenetics. Further applications, such as transparent penetrating electrode arrays, multi-electrode electroretinography, and electromyography, are also viable with this technology. The procedures described herein, from the material characterization methods to the optogenetic experiments, can be completed within 3–4 weeks by an experienced graduate student. These protocols should help to expand the boundaries of neurophysiological experimentation, enabling analytical methods that were previously unachievable using opaque metal–based electrode arrays.

In this work, liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated for screening and confirmation of 64 illicit compounds in dietary supplements. The target compounds were illegally used pharmaceutical drugs, prohibited compounds, and not authorized ingredients for different therapeutics (sexual enhancement, weight loss, muscular strengthening, and relaxing products). The validation procedure was performed to evaluate selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision according to the Association of Official Analytical Chemists guidelines. The linearity was >0.98 in the range of 0.5–200 µg L−1. The LOQs were in the range 1–10 µg kg−1 for all target compounds. The accuracy (expressed as recovery) was 78.5–114%. The precision (expressed as the relative standard deviation) was below 9.15%. The developed method was applied for the determination of illicit compounds in dietary supplements collected from websites. As a result, the total detection rate was 13.5% (27 samples detected in 200 samples). The concentrations of detected samples ranged from 0.51 to 226 mg g−1. The proposed methodology is suitable for monitoring the adulteration of illicit compounds in dietary supplements.

SHARPIN, an adaptor for the linear ubiquitin chain assembly complex (LUBAC), plays important roles in NF-κB signaling and inflammation. Here, we have demonstrated a LUBAC-independent role for SHARPIN in regulating melanoma growth. We observed that SHARPIN interacted with PRMT5, a type II protein arginine methyltransferase, and increased its multiprotein complex and methyltransferase activity. Activated PRMT5 controlled the expression of the transcription factors SOX10 and MITF by SHARPIN-dependent arginine dimethylation and inhibition of the transcriptional corepressor SKI. Activation of PRMT5 by SHARPIN counteracted PRMT5 inhibition by methylthioadenosine, a substrate of methylthioadenosine phosphorylase, which is codeleted with cyclin-dependent kinase inhibitor 2A (CDKN2A) in approximately 15% of human cancers. Collectively, we identified a LUBAC-independent role for SHARPIN in enhancing PRMT5 activity that contributes to melanomagenesis through the SKI/SOX10 regulatory axis.

BackgroundLess is known about the impact of cancer on household assets and household financial portfolio during which cancer survivors face higher mortality risk. Economic theory predicts that cancer survivors would deplete their wealth in such a way that meets immediate financial needs for treatment and that hedges the risk of anticipated medical expenses associated with recurrence. Building upon this prediction, we examine long-term changes in household assets in response to cancer diagnosis among middle-aged and elderly Americans (age ≥ 50).ResultsUsing the 2000–2014 waves of the Health and Retirement Study, we estimated the household fixed effects regression that regresses household assets on time elapsed since cancer diagnosis (≤ 2 years, > 2 but ≤4 years, > 4 but ≤6 years, and > 6 but ≤8 years). Regression estimates were adjusted for demographic characteristics, general health condition, employment outcomes, and household economic attributes. Household assets were measured by total net worth as well as the amount of savings held in each asset category. The loss of household assets attributable to cancer was estimated to be $125,832 in 2015 dollars per household with a cancer patient. This change came from statistically significant reductions in investment assets, miscellaneous savings, real estate equity, and business equity, and increases in unsecured debt. We also found 17.2–28.0% increases in cash and cash-equivalent assets from + 2 years since diagnosis through the rest of the study periods. The accumulation of cash was observed for both the well-insured group (multiple coverages) and those with limited insurance (single coverage).ConclusionsThe results showed evidence of both asset depletion and precautionary accumulation of liquid assets among cancer survivors, which reduces risk exposure of household financial portfolio. Our findings highlighted that household asset is an important source of liquidity to finance cancer care and to absorb the expected expenditure risk associated with cancer recurrence. We also showed that health insurance provides limited coverage of health risks associated with cancer.

Fouling mechanisms associated with membrane-based polysaccharide enrichment were determined using a dense ultrafiltration (UF) membrane. Dextran with different molecular weights (MWs) was used as a surrogate for polysaccharides. The influence of dextran MW on fouling mechanisms was quantified using the Hermia model. Flux data obtained with different dextran MWs and filtration cycles were plotted to quantify the more appropriate fouling mechanisms among complete pore blocking, standard pore blocking, intermediate pore blocking, and cake filtration. For 100,000 Da dextran, all four mechanisms contributed to the initial fouling. As the filtration progressed, the dominant fouling mechanism appeared to be cake filtration with a regression coefficient (R2) of approximately 0.9519. For 10,000 Da, the R2 value for cake filtration was about 0.8767 in the initial filtration. Then, the R2 value gradually decreased as the filtration progressed. For 6000 Da, the R2 values of the four mechanisms were very low in the initial filtration. However, as the filtration progressed, the R2 value for cake filtration reached 0.9057. These results clearly show that the fouling mechanism of dense UF membranes during polysaccharide enrichment can be quantified. In addition, it was confirmed that the dominant fouling mechanism can change with the size of the polysaccharide and the duration of filtration.

Nitrosamines can be produced during the manufacture of rubber-type products such as pacifiers or the nipples of baby bottles. Humans can be exposed to the nitrosamines in these products when they are eluted into saliva. In this study, we compared the efficiency of electron impact ionization (EI), atmospheric pressure chemical ionization (APCI), and electrospray ionization (ESI) methods for the analysis of nine nitrosamines eluted into artificial saliva. In addition, nine nitrosamines eluted from 54 rubber-type products (rubber, thermoplastic elastomer, thermoplastic polyurethane, and polyurethane) marketed in Korea were monitored. Finally, non-carcinogenic and carcinogenic risk assessments of oral exposure to nine nitrosamines were performed based on the monitoring results. EI-GC-MS/MS performed the best for the simultaneous analysis of these nine nitrosamines with respect to overall linearity, trace analysis limit of detection (less than 1 μg), recovery (average 108.66 ± 9.32%), and precision (less than 6%), compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS) (APCI and ESI) methods. Using the EI-GC-MS/MS method, these nine nitrosamines eluted into artificial saliva from 54 rubber-type products were monitored. Based on the monitoring data, risk assessment was performed by calculating the margin of exposure (MOE) for the respective nitrosamines detected. As a result, these nitrosamines were confirmed to be safe with regard to both non-carcinogenic and carcinogenic risks.

This study examined the role of personality traits in the receipt of financial help at older ages using the 2006 and 2008 waves of Health and Retirement Study data. An investigation of (1) how the five domains of personality traits (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism) are associated with the receipt of financial help among older adults and (2) the relationship between personality traits and the source of financial help received was examined. Three sets of probit analyses were conducted. The results indicated that personality can predict financial help and the source of financial help. Specifically, older adults who exhibited relatively higher levels of neuroticism and agreeableness were more likely to receive financial help, whereas those who exhibited relatively higher levels of conscientiousness were less likely to receive financial help regardless of the source. Furthermore, older adults who had relatively higher levels of neuroticism were more likely to help themselves with individual sources such as credit cards whereas agreeable older adults were more likely to receive financial help from family members. These findings have implications for financial counseling, planning and education professionals, public assistance program directors, and policy makers. Understanding the effect of personality on financial decision-making can help with financial planning throughout life and inform outreach efforts for those in need of financial help.