Low Accumulation Research Articles

Noise filtering options for conically scanning Doppler lidar measurements with low pulse accumulation

Abstract. Doppler lidar (DL) applications with a focus on turbulence measurements sometimes require measurement settings with a relatively small number of accumulated pulses per ray in order to achieve high sampling rates. Low pulse accumulation comes at the cost of the quality of DL radial velocity estimates and increases the probability of outliers, also referred to as “bad” estimates or noise. Careful filtering is therefore the first important step in a data processing chain that begins with radial velocity measurements as DL output variables and ends with turbulence variables as the target variable after applying an appropriate retrieval method. It is shown that commonly applied filtering techniques have weaknesses in distinguishing between “good” and “bad” estimates with the sensitivity needed for a turbulence retrieval. For that reason, new ways of noise filtering have been explored, taking into account that the DL background noise can differ from generally assumed white noise. It is shown that the introduction of a new coordinate frame for a graphical representation of DL radial velocities from conical scans offers a different perspective on the data when compared to the well-known velocity–azimuth display (VAD) and thus opens up new possibilities for data analysis and filtering. This new way of displaying DL radial velocities builds on the use of a phase-space perspective. Following the mathematical formalism used to explain a harmonic oscillator, the VAD’s sinusoidal representation of the DL radial velocities is transformed into a circular arrangement. Using this kind of representation of DL measurements, bad estimates can be identified in two different ways: either in a direct way by singular point detection in subsets of radial velocity data grouped in circular rings or indirectly by localizing circular rings with mostly good radial velocity estimates by means of the autocorrelation function. The improved performance of the new filter techniques compared to conventional approaches is demonstrated through both a direct comparison of unfiltered with filtered datasets and a comparison of retrieved turbulence variables with independent measurements.

Drivers of organic carbon distribution and accumulation in the northern Barents Sea

Sedimentary properties and accumulation rates on the continental shelf and in the deep sea reflect temporal oceanographic, biological and chemical processes occurring in the water column and the sediment surface. We used the radionuclides 210Pb, 226Ra, and 137Cs activities to estimate sedimentation rates during the last century at nine stations in the northern Barents Sea region. Elemental (C, N) and stable isotopic composition (δ13C, δ15N) were also analysed from the nine stations sampled in August 2018, and, for five other stations sampled in August and December 2019, and in March and May 2021. Sediment accumulation rates varied between 130 and 1 410 g m−2 y−1. The < 63 μm normalized total organic carbon (TOC63) and the total nitrogen from the sediment surface varied between 0.90–2.56 % and 0.13–0.33 %, respectively. Ice-free shelf stations had higher TOC63 and possibly fresher organic matter (high δ13C, low δ15N) than ice-covered more northern stations. The opposite trend was observed for total inorganic carbon. We found that these trends in biogeochemical parameters were spatially structured by the winter sea ice concentration and biological production differences, and exhibited a south-north separation of the Polar Front region. The low and stable organic carbon accumulation rate (1.7–13.4 g Corg m-2 y−1; ARtoc) is a function of slow sedimentation rates, and high degradation and residence time in the water column and at the sediment–water interface. Overall, the ARtoc has been stable for the past 100 years, with a slight increase from the early 1970s to the present at the shelf and slope stations. Our results highlight that spatial scales of variability of the studied sedimentary parameters are linked to spatial patterns of important environmental variables (e.g., chlorophyll-a, sea ice concentration) in the region. In contrast, no seasonal differences were observed in the sediment parameters of revisited stations, and the dated sediment geochemical profiles did not exhibit substantial longer-term variation. This means that climate-induced changes in variables that modify the sedimentary geochemistry of the environment may affect benthic community activity and structure before leaving a record in ARtoc.

Electron transferring with oxygen defects on Ni-promoted Pd/Al2O3 catalysts for low-temperature lean methane combustion

Methane (CH4) is the second most consequential greenhouse gas after CO2, with a substantial global warming potential. The CH4 catalytic combustion offers an efficient method for the elimination of CH4. However, improving the catalytic performance of Pd-based materials for low-temperature CH4 combustion remains a big challenge. In this study, we synthesized an enhanced Pd/5NiAlOx catalyst that demonstrated superior catalytic activity and improved water resistance compared to the Pd/Al2O3 catalyst. Specifically, the T90 was decreased by over 100 °C under both dry and wet conditions. Introducing Ni resulted in an enormously enhanced number of oxygen defects on the obtained 5NiAlOx support. This defect-rich support facilitates the anchoring of PdO through increased electron transfer, thereby inhibiting the production of high-valence Pd(2+δ)+ and stimulating the generation of unsaturated Pd sites. Pd0 can effectively activate surface oxygen and PdO plays a significant role in activating CH4, resulting in high activity for Pd/5NiAlOx. On the other hand, the increased water resistance of Pd/5NiAlOx was mainly due to the generation of *OOH species and the lower accumulation of surface -OH species during the reaction process.

Distinct Gut Microbiota and Arachidonic Acid Metabolism in Obesity-Prone and Obesity-Resistant Mice with a High-Fat Diet.

An imbalance of energy intake and expenditure is commonly considered as the fundamental cause of obesity. However, individual variations in susceptibility to obesity do indeed exist in both humans and animals, even among those with the same living environments and dietary intakes. To further explore the potential influencing factors of these individual variations, male C57BL/6J mice were used for the development of obesity-prone and obesity-resistant mice models and were fed high-fat diets for 16 weeks. Compared to the obesity-prone mice, the obesity-resistant group showed a lower body weight, liver weight, adipose accumulation and pro-inflammatory cytokine levels. 16S rRNA sequencing, which was conducted for fecal microbiota analysis, found that the fecal microbiome's structural composition and biodiversity had changed in the two groups. The genera Allobaculumbiota, SMB53, Desulfovibrio and Clostridium increased in the obesity-prone mice, and the genera Streptococcus, Odoribacter and Leuconostoc were enriched in the obesity-resistant mice. Using widely targeted metabolomics analysis, 166 differential metabolites were found, especially those products involved in arachidonic acid (AA) metabolism, which were significantly reduced in the obesity-resistant mice. Moreover, KEGG pathway analysis exhibited that AA metabolism was the most enriched pathway. Significantly altered bacteria and obesity-related parameters, as well as AA metabolites, exhibited strong correlations. Overall, the phenotypes of the obesity-prone and obesity-resistant mice were linked to gut microbiota and AA metabolism, providing new insight for developing an in-depth understanding of the driving force of obesity resistance and a scientific reference for the targeted prevention and treatment of obesity.

#1451 Calcimimetics reduce the progression of high-phosphate diet-induced tubular damage

Abstract Background and Aims During chronic kidney disease (CKD) progresses, there is an increased phosphate load and the concentration of the phosphaturic hormones PTH and FGF23 rises. In patients, phosphate and FGF23 are discussed as risk factors for CKD progression. We have recently shown that mice with high phosphate, PTH and FGF23 levels develop Stat3/Kim-1-mediated proximal tubule damage and tubulointerstitial fibrosis associated with increased MCP-1 expression and accumulation of macrophages. Calcimimetics lower PTH and FGF23 levels in hemodialysis patients and are thought to have both cardio- and nephroprotective effects. In a preclinical study, cinacalcet was shown to stabilize podocyte function in proteinuric mice. Therefore, we postulate that calcimimetics also have a positive effect on the progression of tubular damage in mice with high phosphate, PTH and FGF23 levels. Method For the induction of phosphaturic hormones with concomitant tubule damage, male C57BL/6 mice were fed a 2.0% high phosphate diet (HPD) and compared to animals on a 0.8% control phosphate diet (CPD). After four months, one HPD group was additionally treated with 1 mg/kg body weight/day etelcalcetide (KP-2326). Six months after the start of the trial, blood and urine samples as well as kidneys were taken for biochemical, histological and molecular biological examinations. Results KP-2326 treatment reduced HPD-induced PTH and FGF23 levels, but had no effect on increased phosphate excretion or elevated serum phosphate levels. Histologically, tubular damage was not as pronounced in the KP-2326-treated HPD animals as in the HPD group without therapy. The increased BUN levels caused by HPD and the albuminuria were significantly reduced by KP-2326. KP-2326 reduced HPD-mediated activation of Stat3 in proximal tubule cells and decreased Kim-1 synthesis at both mRNA and protein levels. Moreover, KP-2326 significantly reduced the mRNA expression of Ccl2 and the macrophage-specific marker Adgre1 compared to the untreated HPD group, which was histologically reflected in a lower accumulation of F4/80+ macrophages around the damaged tubules. Conclusion Treatment with KP-2326 was able to reduce the progression of HPD-induced tubule damage, at least in part due to the reduction in PTH and FGF23 levels.

A Novel TGFβ Receptor Inhibitor, IPW-5371, Prevents Diet-induced Hepatic Steatosis and Insulin Resistance in Irradiated Mice.

As the number of cancer survivors increases and the risk of accidental radiation exposure rises, there is a pressing need to characterize the delayed effects of radiation exposure and develop medical countermeasures. Radiation has been shown to damage adipose progenitor cells and increase liver fibrosis, such that it predisposes patients to developing metabolic-associated fatty liver disease (MAFLD) and insulin resistance. The risk of developing these conditions is compounded by the global rise of diets rich in carbohydrates and fats. Radiation persistently increases the signaling cascade of transforming growth factor β (TGFβ), leading to heightened fibrosis as characteristic of the delayed effects of radiation exposure. We investigate here a potential radiation medical countermeasure, IPW-5371, a small molecule inhibitor of TGFβRI kinase (ALK5). We found that mice exposed to sub-lethal whole-body irradiation and chronic Western diet consumption but treated with IPW-5371 had a similar body weight, food consumption, and fat mass compared to control mice exposed to radiation. The IPW-5371 treated mice maintained lower fibrosis and fat accumulation in the liver, were more responsive to insulin and had lower circulating triglycerides and better muscle endurance. Future studies are needed to verify the improvement by IPW-5371 on the structure and function of other metabolically active tissues such as adipose and skeletal muscle, but these data demonstrate that IPW-5371 protects liver and whole-body health in rodents exposed to radiation and a Western diet, and there may be promise in using IPW-5371 to prevent the development of MAFLD.

Oil Palm AP2 Subfamily Gene EgAP2.25 Improves Salt Stress Tolerance in Transgenic Tobacco Plants.

AP2/ERF transcription factor genes play an important role in regulating the responses of plants to various abiotic stresses, such as cold, drought, high salinity, and high temperature. However, less is known about the function of oil palm AP2/ERF genes. We previously obtained 172 AP2/ERF genes of oil palm and found that the expression of EgAP2.25 was significantly up-regulated under salinity, cold, or drought stress conditions. In the present study, the sequence characterization and expression analysis for EgAP2.25 were conducted, showing that it was transiently over-expressed in Nicotiana tabacum L. The results indicated that transgenic tobacco plants over-expressing EgAP2.25 could have a stronger tolerance to salinity stress than wild-type tobacco plants. Compared with wild-type plants, the over-expression lines showed a significantly higher germination rate, better plant growth, and less chlorophyll damage. In addition, the improved salinity tolerance of EgAP2.25 transgenic plants was mainly attributed to higher antioxidant enzyme activities, increased proline and soluble sugar content, reduced H2O2 production, and lower MDA accumulation. Furthermore, several stress-related marker genes, including NtSOD, NtPOD, NtCAT, NtERD10B, NtDREB2B, NtERD10C, and NtP5CS, were significantly up-regulated in EgAP2.25 transgenic tobacco plants subjected to salinity stress. Overall, over-expression of the EgAP2.25 gene significantly enhanced salinity stress tolerance in transgenic tobacco plants. This study lays a foundation for further exploration of the regulatory mechanism of the EgAP2.25 gene in conferring salinity tolerance in oil palm.

Unearthing the legacy of wildfires: post fire pyrogenic carbon and soil carbon persistence across complex Pacific Northwest watersheds

Wildfires have the potential to dramatically alter the carbon (C) storage potential, ecological function, and the fundamental mechanisms that control the C balance of Pacific Northwest (PNW) forested ecosystems. In this study, we explored how wildfire influences processes that control soil C stabilization and the consequent soil C persistence, and the role of previous fire history in determining soil C fire response dynamics. We collected mineral soils at four depth increments from burned (low, moderate, and high soil burn severity classes) and unburned areas and surveyed coarse woody debris (CWD) in sites within the footprint of the 2020 Holiday Farm Fire and in surrounding Willamette National Forest and the H.J. Andrews Experimental Forest. We found few changes in overall soil C pools as a function of fire severity; we instead found that unburned sites contained high levels of pyrogenic C (PyC) that were commensurate with PyC concentrations in the high severity burn sites—pointing to the high background rate of fire in these ecosystems. An analysis of historical fire events lends additional support, where increasing fire count is loosely correlated with increasing PyC concentration. An unexpected finding was that PyC concentration was lower in low soil burn severity sites than in control sites, which we attribute to fundamental ecological differences in regions that repeatedly burn at high severity compared with those that burn at low severity. Our CWD analysis showed that high mean fire return interval (decades between fire events) was strongly correlated with low annual CWD accumulation rate; whereas areas that burn frequently had a high annual CWD accumulation rate. Within the first year postfire, trends in soil density fractions demonstrated no significant response to fire for the mineral-associated organic matter pool but slight increases in the particulate pool with increasing soil burn severity—likely a function of increased charcoal additions. Overall, our results suggest that these PNW forest soils display complex responses to wildfire with feedbacks between CWD pools that provide varying fuel loads and a mosaic fire regime across the landscape. Microclimate and historic fire events are likely important determinants of soil C persistence in these systems.

The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis

ObjectiveSimultaneous activation of β2- and β3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of β1-ARs – and thus inducing cardiovascular complications – are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel β2-and β3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models. MethodsIn the developmental phase, we assessed the impact of ATR-127's on cAMP accumulation in relation to the non-selective β-AR agonist isoprenaline across various rodent β-AR subtypes, including neonatal rat cardiomyocytes. Following these experiments, L6 muscle cells were stimulated with ATR-127 to assess the impact on GLUT4-mediated glucose uptake and intramyocellular cAMP accumulation. Additionally, in vitro, and in vivo assessments are conducted to measure ATR-127's effects on BAT glucose uptake and thermogenesis. Finally, diet-induced obese mice were treated with 5 mg/kg ATR-127 for 21 days to investigate the effects on glucose homeostasis, body weight, fat mass, skeletal muscle glucose uptake, BAT thermogenesis and hepatic steatosis. ResultsExposure of L6 muscle cells to ATR-127 robustly enhanced GLUT4-mediated glucose uptake despite low intramyocellular cAMP accumulation. Similarly, ATR-127 markedly increased BAT glucose uptake and thermogenesis both in vitro and in vivo. Prolonged treatment of diet-induced obese mice with ATR-127 dramatically improved glucose homeostasis, an effect accompanied by decreases in body weight and fat mass. These effects were paralleled by an enhanced skeletal muscle glucose uptake, BAT thermogenesis, and improvements in hepatic steatosis. ConclusionsOur results demonstrate that ATR-127 is a highly effective, novel β2- and β3-ARs agonist holding great therapeutic promise for the treatment of obesity and its comorbidities, whilst potentially limiting cardiovascular complications. As such, the therapeutic effects of ATR-127 should be investigated in more detail in clinical studies.

A Whole Plant Analysis of Chloride and Sodium Exclusion Using a Range of Grapevine Rootstock Genotypes

Background and Aims. Salt exclusion is an important attribute for wine grapes since many countries have limits to the concentration of sodium (Na+) and/or chloride (Cl−) tolerated in wine. The aim was to investigate whole plant capacity for Na+ and Cl‾ exclusion and the within-plant partitioning of accumulated ions to better understand these important salt tolerance traits. Methods and Results. Rooted cuttings of 140 Ruggeri and K51-40 (good and poor shoot Cl− excluders, respectively) and five hybrids from a cross between the two genotypes were used. When challenged with salinity, 140 Ruggeri limited the accumulation of Cl− and Na+ in the stem, petioles, and laminae and had a significantly lower whole plant concentration of Cl− and Na+ when compared to K51-40. The latter indicates that 140 Ruggeri accumulates less Cl− and Na+ than K51-40 by a lower uptake or a potentially greater efflux by roots, or both. While K51-40 accumulated significantly more Na+, it was able to retrieve it from the xylem; store it in the roots, stem, and petiole; and keep the lamina concentration comparable to that of 140 Ruggeri. Petioles of all genotypes appeared to play a role in limiting Cl− accumulation in laminae and particularly for K51-40, to limit Na+ accumulation in laminae. Conclusions. The grapevine capacity for Cl− and Na+ exclusion can be defined primarily as the lower net accumulation on a whole plant basis, reflecting the difference between the uptake and any efflux that may occur. Lower root to shoot transport is a key factor in shoot Cl− and Na+ exclusion. Petiole accumulation assists in limiting the Cl− and Na+ accumulation in the laminae. Significance of the Study. The study addressed the knowledge gap by examining Cl− and Na+ exclusion on a whole plant basis, highlighting a range of within-plant mechanisms that act in limiting the accumulation of both ions in the laminae.

Low blood glucose and fatigue accumulation at peak hours of occupational trauma in secondary industry workers

Objectives. The incidence of occupational traumatic injuries caused by human error has been reported to occur at 11:00 and 8–9 h after commencing work. Impaired attention is closely related to the incidence of these accidents. Therefore, this study aimed to clarify the changes in blood glucose, fatigue and stress response hormone levels over time among workers in a secondary industry. Methods. The blood glucose and subjective fatigue levels of 26 male secondary-industry workers were measured on workdays. In addition, the cortisol and dehydroepiandrosterone levels in saliva were measured on one workday and one holiday. Results. Blood glucose levels at 11:00 and 17:30 on the workday were significantly lower than those at 09:30. Moreover, hypoglycemia was observed in some participants. A significant increase in subjective fatigue levels was observed during the workday. However, no significant differences in salivary cortisol levels were observed between the workday and the holiday at any time point. Conclusions. Blood glucose levels decreased and subjective fatigue levels increased at the time points that occupational accidents were reported to occur most frequently during work. These factors may contribute to human errors due to impaired attentional function.

Foliar uptake screening: A promising strategy for identifying wheat varieties with low lead accumulation

Lead (Pb) contamination in wheat grain is of great concern, especially in North China. Atmospheric deposition is a major contributor to Pb accumulation in wheat grain. Screening low Pb accumulating wheat varieties has been an effective method for addressing Pb contamination in wheat grain. However, identifying wheat varieties with low Pb accumulation based on foliar uptake of atmospheric Pb has been neglected. Therefore, two field trials with distinct atmospheric Pb deposition were conducted to screen for stable varieties with low Pb accumulation. It was verified that YB700 and CH58, which have high thousand-grain weights and stable low Pb accumulation in field 1 (0.19 and 0.13 mg kg−1) and field 2 (0.17 and 0.20 mg kg−1), respectively, were recommended for cultivation in atmospheric Pb contaminated farmlands in North China. Furthermore, indoor experiments were conducted to investigate Pb uptake by the roots and leaves of different wheat varieties. Our findings indicate that Pb accumulation in different wheat varieties is primarily influenced by foliar Pb uptake rather than root Pb uptake. Interestingly, there was a positive correlation (p < 0.05) between the Pb concentrations in leaves and the stomatal width and trichome length of the adaxial epidermal surface. Additionally, there is a positive correlation (p < 0.01) between the Pb concentration in the wheat grain and trichome length. In conclusion, the screening of wheat varieties with narrower stomatal widths or shorter trichomes based on foliar uptake pathways is an effective strategy for ensuring food safety in areas contaminated by atmospheric Pb.

In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells

Three years after SARS-CoV-2 emerged as a global infectious threat, the virus has become endemic. The neurological complications such as depression, anxiety, and other CNS complications after COVID-19 disease are increasing. The brain, and CSF have been shown as viral reservoirs for SARS-CoV-2, yielding a potential hypothesis for CNS effects. Thus, we investigated the CNS pharmacology of orally dosed nirmatrelvir/ritonavir (NMR/RTV). Using both an in vitro and an in vivo rodent model, we investigated CNS penetration and potential pharmacodynamic activity of NMR. Through pharmacokinetic modeling, we estimated the median CSF penetration of NMR to be low at 18.11% of plasma with very low accumulation in rodent brain tissue. Based on the multiples of the 90% maximal effective concentration (EC90) for SARS-CoV-2, NMR concentrations in the CSF and brain do not achieve an exposure level similar to that of plasma. A median of only 16% of all the predicted CSF concentrations in rats were > 3xEC90 (unadjusted for protein binding). This may have implications for viral persistence and neurologic post-acute sequelae of COVID-19 if increased NMR penetration in the CNS leads to decreased CNS viral loads and decreased CNS inflammation.

Identification of Iodotyrosines as Novel Substrates for the Thyroid Hormone Transporter MCT8.

Background: Monocarboxylate transporter 8 (MCT8) is the most specific thyroid hormone transporter identified to date, deficiency of which has been associated with severe intellectual and motor disability and abnormal serum thyroid function tests. However, it is presently unknown if MCT8, similar to other thyroid hormone transporters, also accepts additional substrates, and if disruption of their transport may contribute to the observed phenotype. Methods: In this study, we aimed to identify such substrates by applying liquid chromatography-mass spectrometry-based metabolome analysis in lysates of control and MCT8-overexpressing Xenopus oocytes. A subset of identified candidate substrates were validated by direct transport studies in transiently transfected COS-1 cells and human fibroblasts, which endogenously express MCT8. Moreover, transport characteristics were determined, including transport saturation and cis-inhibition potency of thyroid hormone transport. Results: Metabolome analysis identified 21 m/z ratios, corresponding to 87 candidate metabolites, with a 2.0-times differential abundance in MCT8-injected oocytes compared with controls. These metabolites included 3,5-diiodotyrosine (DIT) and several amino acids, including glutamate and glutamine. In accordance, MCT8-expressing COS-1 cells had 2.2-times lower intracellular accumulation of [125I]-DIT compared with control cells. This effect was largely blocked in the presence of 3,3',5-triiodothyronine (T3) (IC50: 2.5 ± 1.5 µM) or thyroxine (T4) (IC50: 5.8 ± 1.3 µM). Conversely, increasing concentrations of DIT enhanced the accumulation of T3 and T4. The MCT8-specific inhibitor silychristin increased the intracellular accumulation of DIT in human fibroblasts. COS-1 cells expressing MCT8 also exhibited a 50% reduction in intracellular accumulation of [125I]-3-monoiodotyrosine (MIT). In contrast, COS-1 cells expressing MCT8 did not alter the intracellular accumulation of [3H]-glutamate or [3H]-glutamine. However, studies in human fibroblasts showed a 1.5-1.9 times higher glutamate uptake in control fibroblasts compared with fibroblasts derived from patients with MCT8 deficiency, which was not affected in the presence of silychristin. Conclusions: Taken together, our results suggest that the iodotyrosines DIT and MIT can be exported by MCT8. MIT and DIT interfere with MCT8-mediated transport of thyroid hormone in vitro and vice versa. Future studies should elucidate if MCT8, being highly expressed in thyroidal follicular cells, also transports iodotyrosines invivo.

CD74 supports accumulation and function of regulatory T cells in tumors

Regulatory T cells (Tregs) are plastic cells playing a pivotal role in the maintenance of immune homeostasis. Tregs actively adapt to the microenvironment where they reside; as a consequence, their molecular and functional profiles differ among tissues and pathologies. In tumors, the features acquired by Tregs remains poorly characterized. Here, we observe that human tumor-infiltrating Tregs selectively overexpress CD74, the MHC class II invariant chain. CD74 has been previously described as a regulator of antigen-presenting cell biology, however its function in Tregs remains unknown. CD74 genetic deletion in human primary Tregs reveals that CD74KO Tregs exhibit major defects in the organization of their actin cytoskeleton and intracellular organelles. Additionally, intratumoral CD74KO Tregs show a decreased activation, a drop in Foxp3 expression, a low accumulation in the tumor, and consistently, they are associated with accelerated tumor rejection in preclinical models in female mice. These observations are unique to tumor conditions as, at steady state, CD74KO-Treg phenotype, survival, and suppressive capacity are unaffected in vitro and in vivo. CD74 therefore emerges as a specific regulator of tumor-infiltrating Tregs and as a target to interfere with Treg anti-tumor activity.

Hydrology and oxygen addition drive nutrients, metals, and methylmercury cycling in a hypereutrophic water supply reservoir

Impaired water quality in Mediterranean climate reservoirs is mainly associated with eutrophication and internal nutrient loading. To improve water quality in hypereutrophic Hodges Reservoir, California, United States, a hypolimnetic oxygenation system (HOS), using pure oxygen gas, was implemented in 2020. This study encompasses 3 years of pre-oxygenation data (2017–2019) and 2 years of post-oxygenation data (2020–2021) to understand the cycling of nutrients, metals, and mercury in the reservoir. During the wet year of 2017, mildly reduced conditions lasted until mid-summer in the enlarged reservoir. Nutrients and metals were seen in the hypolimnion including ammonia (~2 mg-N/L), manganese (~0.5 mg/L), phosphate (~0.5 mg-P/L), and sulfide (~10 mg/L). Production of methylmercury (MeHg), an important bioaccumulative toxin, was favored from April to June with a hypolimnetic accumulation rate of around 200 ng/m2·d. In contrast, the dry year of 2018 exhibited higher hypolimnetic concentrations of ammonia (~4 mg-N/L), manganese (~1 mg/L), phosphate (&amp;gt;0.5 mg-P/L), and sulfide (&amp;gt;15 mg/L). The rapid onset of highly reduced conditions in 2018 corresponded with low MeHg hypolimnetic accumulation (~50 ng/m2·d). It seems that mildly reduced conditions were associated with higher MeHg accumulation, while sulfidic, reduced conditions impaired inorganic mercury bioavailability for MeHg production and/or promoted microbial demethylation. Sulfide also appeared to act as a sink for iron via FeS precipitation, and potentially for manganese via MnS precipitation or manganese coprecipitation with FeS. Mass flux estimates for 2017–2019 indicate that much of the nutrients that accumulated in the hypolimnion moved via turbulent diffusion into the epilimnion at loading rates far exceeding thresholds predicting eutrophic conditions. After oxygenation in 2020–2021, the reservoir water column was highly oxidized but showed a lack of thermal stratification, suggesting reservoir operations in combination with HOS implementation inadvertently mixed the water column in this relatively shallow reservoir. Post-oxygenation, concentrations of ammonia, phosphate, manganese, and mercury in bottom waters all decreased, likely in response to oxidized conditions. Oxygenated bottom waters exhibited elevated nitrate, a byproduct of ammonia nitrification, and iron, a byproduct of FeS oxidation, indicating a lake-wide response to oxygenation.

Risk assessment of trace elements in vegetables grown in river Yamuna floodplain in Delhi.

Urban agriculture is common in fertile river floodplains of many developing countries. However, there is a risk of contamination in highly polluted regions. This study quantifies health risks associated with the consumption of vegetables grown in the floodplain of the urban river 'Yamuna' in the highly polluted yet data-scarce megacity Delhi, India. Six trace elements are analyzed in five kinds of vegetable samples. Soil samples from the cultivation area are also analyzed for elemental contamination. Ni, Mn, and Co are observed to be higher in leafy vegetables than others. Fruit and inflorescence vegetables are found to have higher concentrations of Cr, Pb, and Zn as compared to root vegetables. Transfer Factor indicates that Cr and Co have the highest and least mobility, respectively. Vegetable Pollution Index indicates that contamination levels follow as Cr > Ni > Pb > Zn. Higher Metal Pollution Index of leafy and inflorescence vegetables than root and fruit vegetables indicate that atmospheric deposition is the predominant source. Principal Component Analysis indicates that Pb and Cr have similar sources and patterns in accumulation. Among the analyzed vegetables, radish may pose a non-carcinogenic risk to the age group of 1-5year. Carcinogenic risk is found to be potentially high due to Ni and Cr accumulation. Consumption of leafy vegetables was found to have relatively less risk than other vegetables due to lower Cr accumulation. Remediation of Cr and Ni in floodplain soil and regular monitoring of elemental contamination is a priority.

Synthesis and Preclinical Evaluation of Urea-Based Prostate-Specific Membrane Antigen-Targeted Conjugates Labeled with 177Lu.

177Lu-labeled small-molecule prostate-specific membrane antigen (PSMA) targeted tracers are therapeutic agents for metastatic castration-resistant prostate cancer. Optimizing molecular design holds the potential to further enhance the pharmacokinetic properties of PSMA-targeted agents while preserving their potent therapeutic effects. In this study, six novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL) urea-based PSMA ligand 2,2',2″,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid conjugates were synthesized. These conjugates feature polypeptide linkers containing the Phe-Phe peptide sequence and an aromatic fragment at the ε-NH-Lys group of the DCL fragment. The synthesis yielded products with satisfactory yields ranging from 60% to 72%, paving the way for their preclinical evaluation. The labeling of the new variants of urea-based PSMA inhibitors provided a radiochemical yield of over 95%. The 177Lu-labeled conjugates demonstrated specific and moderate affinity binding to PSMA-expressing human cancer cells PC3-pip in vitro and specific accumulation in PSMA-expressing xenografts in vivo. Based on the results, both the lipophilicity and the type of substituent in the linker significantly influence the binding properties of the PSMA inhibitor and its biodistribution profile. Specifically, the studied variants containing a bromine substituent or a hydroxyl group introduced into the aromatic fragment of the phenylalanyl residue in DCL exhibit higher affinities to PSMA compared to variants with only a chlorine-substituted aromatic fragment or variants without any substituents. The [177Lu]Lu-13C with the bromine substituent was characterized by the highest activity accumulation in blood, salivary glands, muscle, bone, and gastrointestinal tract and had inasmuch as an unfavorable pharmacokinetic profile. The negative charge of the carboxyl group in the phenyl moiety of the [177Lu]Lu-13A variant has demonstrated a positive effect on reducing the retention of activity in the liver and the kidneys (the ratio of tumor to kidneys was 1.3-fold). Low accumulation in normal tissues in vivo indicates that this novel PSMA-targeting inhibitor is a promising radioligand.

CRISPR-mediated BnaNRAMP1 homologous copies editing create a low Cd-accumulation oilseed rape germplasm with unaffected yield

Brassica napus, one of the most important oil crops cultivated globally, is severely impacted by prolonged soil contamination with cadmium (Cd), resulting in decreased yields and poor seed quality. This crop exhibits a high adsorption capacity for Cd, thereby making the creation of seed resources with low Cd-accumulation as an essential strategy to alleviate this challenge. To address this issue, we genetically edited BnaNRAMP1 in B. napus by targeting three different exon regions, resulting in new germplasm resources with significant differences in Cd accumulation capacity and unaffected yield. Among these, the mutant K140-22, specifically targeting the seventh exon, is distinguished by its substantially reduced Cd accumulation. Further, enzyme assays of the antioxidant defense system in both roots and shoots of K140-22 revealed its enhanced antioxidant activity, which contributes to elucidate the molecular mechanisms of plant tolerance to heavy metal stress. Remarkably, this mutant also maintained equivalent agronomic traits and seed quality, which highlights its potential as a germplasm resource for rapeseed breeding for low Cd accumulation, as well as for elevating rapeseed economic value in Cd contaminated soil.

Abstract 150: Decoding The Variant-to-function Relationship For LIPA , A Risk Locus For Cad

Background: Genome-wide association studies (GWASs) link genetic variation in the LIPA (lysosomal acid lipase) gene to coronary artery disease (CAD). Quantitative Trait Loci (QTL) studies indicate higher LIPA mRNA and enzyme activity in the monocytes of risk alleles carriers. Yet, the mechanism whereby this locus confers disease etiology has not been fully established. Herein, we aim to establish the variant-to-function relationship and elucidate how increased LIPA impacts atherosclerosis. Methods: Employing post-GWAS pipelines (eQTL, enzyme activity-QTL, Tri-HiC, luciferase assay, allele-specific binding, motif analysis, and mobility shift assay), we connect functional variants to target genes in causal myeloid cells. Myeloid-specific Lipa overexpression mice ( Lipa Tg ) on Ldlr -/- background were generated and characterized. Results: Post-GWAS pipelines support LIPA as the candidate causal gene at this locus. In human monocyte-derived macrophages, risk allele carriers of GWAS CAD variants exhibit higher LIPA mRNA, protein, and enzyme activity. Tri-HiC and luciferase assay identified an intronic region within LIPA , housing GWAS CAD noncoding variants and exhibiting monocyte-specific enhancer activity. Within the enhancer region, 1412445 and rs1320496 were identified as the two potential causal variants, with the risk alleles having increased enhancer activity in luciferase assay and increased binding to PU.1 in mobility shift assay. Collectively, the above data suggest that the risk alleles of CAD variants lead to increased LIPA in monocytes/macrophages. Consistently, Lipa Tg , Ldlr -/- mice fed a Western diet showed significantly increased lesion size and lesion macrophage area compared to Ctl, Ldlr -/- mice. scRNA-seq analysis followed by functional validation demonstrated that Lipa Tg macrophages had higher free cholesterol yet lower neutral lipid accumulation, accompanied by a transcriptomic signature of increased interferon signaling. Lipa overexpression also increased monocyte infiltration into the plaque. Conclusions: We established that the risk alleles of common noncoding variants at the LIPA locus drive increased myeloid LIPA expression and aggravate atherosclerosis.