Timing of dietary zinc additions during gestation for improved piglet survival.

The objectives of this study were to determine a practical approach to feeding elevated dietary zinc (Zn) to gestating sows in a commercial setting and to confirm preweaning mortality could be reduced by feeding high Zn to sows during different periods of gestation. The study was conducted at a commercial sow farm in the upper Midwest. Mixed parity sows (n = 267) over three consecutive weekly farrowing groups (sows farrowing within 1 wk) were assigned randomly to one of the three dietary treatments within parity. Treatments consisted of: (1) control sows fed a corn-soybean meal diet containing 206 mg/kg total supplemental Zn supplied by zinc hydroxychloride; (2) breed-to-farrow: as control + 147 mg/kg supplemental Zn as ZnSO4 (353 mg/kg total supplemental Zn) fed from 5 d after breeding to farrowing; and (3) day 110-to-farrow: as control fed from breeding to farrowing + 4,079 mg/kg supplemental Zn as ZnSO4 (4,285 mg/kg total supplemental Zn) starting day 110 of gestation until farrowing. At farrowing, individual piglets were weighed and identified within 12 h of birth. Data were analyzed using PROC GLIMMIX of SAS and the model considered the fixed effect of dietary treatment and random effect of farrowing group. Dietary treatments did not affect number of total pigs born per litter. For breed-to-farrow sows, there was an increase in the percentage of pigs born alive compared to sows fed the control and day 110-to-farrow treatments (P < 0.001). The number of stillborn pigs expressed as a percentage of total litter size at birth decreased for breed-to-farrow sows (P < 0.001) compared with control or day 110-to-farrow sows. Mortality of low birth weight piglets from birth to weaning did not differ among dietary treatments (P = 0.305); however, a trend for decreasing post-natal mortality (P = 0.068) of normal birth weight pigs was observed for pigs born to sows fed elevated Zn 5 d before farrowing. In conclusion, feeding elevated Zn to sows throughout gestation increased the proportion of pigs born alive suggesting that elevated gestational Zn intake makes piglets more robust to endure the stresses of farrowing and decreases intrapartum mortality. Under the conditions of this study, elevated Zn intake of sows did not influence piglet post-natal survival. However, feeding high zinc throughout gestation may decrease piglet mortality during the parturition process.

COVID-19 Outcomes in Inflammatory Bowel Disease Hospitalized Patients: A Comprehensive Analysis Using the National Inpatient Sample.

Background: There is no uniformity in the available literature concerning the effects of coronavirus disease 2019 (COVID-19) viral illness on people with inflammatory bowel disease (IBD). Methods: We conducted an analysis using the 2020 National Inpatient Sample (NIS) database to compare the outcomes of COVID-19 hospitalized patients with and without IBD. Results: Of 1,050,040 patients admitted with COVID-19, 5,750 (0.5%) also had IBD. The group with COVID-19 and IBD had higher percentages of females and White individuals and a greater prevalence of chronic lung disease, peripheral vascular disease, and liver disease. However, after accounting for confounding variables, there was no significant difference in mortality rates, length of hospital stays, or hospitalization costs between the two groups. Conclusion: According to our findings, the presence of IBD does not appear to elevate the risk of COVID-19 complications.

Quantitative omics analyses of NCOA4 deficiency reveal an integral role of ferritinophagy in iron homeostasis of hippocampal neuronal HT22 cells.

Introduction: Neurons require iron to support their metabolism, growth, and differentiation, but are also susceptible to iron-induced oxidative stress and cytotoxicity. Ferritin, a cytosolic iron storage unit, mediates cellular adaptation to fluctuations in iron delivery. NCOA4 has been characterized as a selective autophagic cargo receptor facilitating the mobilization of intracellular iron from ferritin. This process named ferritinophagy results in the degradation of ferritin and the consequent release of iron into the cytosol. Methods: Here we demonstrate that NCOA4 is important for the adaptation of the HT22 mouse hippocampal neuronal cell line to cellular iron restriction. Additionally, we determined the pathophysiological implications of impaired ferritinophagy via functional analysis of the omics profile of HT22 cells deficient in NCOA4. Results: NCOA4 silencing impaired ferritin turnover and was cytotoxic when cells were restricted of iron. Quantitative proteomics identified IRP2 accumulation among the most prominent protein responses produced by NCOA4 depletion in HT22 cells, which is indicative of functional iron deficiency. Additionally, proteins of apoptotic signaling pathway were enriched by those responsive to NCOA4 deficiency. Transcriptome profiles of NCOA4 depletion revealed neuronal cell death, differentiation of neurons, and development of neurons as potential diseases and bio functions affected by impaired ferritinophagy, particularly, when iron was restricted. Discussion: These findings identify an integral role of NCOA4-mediated ferritinophagy in the maintenance of iron homeostasis by HT22 cells, and its potential implications in controlling genetic pathways of neurodevelopment and neurodegenerative diseases.

Zinc for infection prevention in children with sickle cell anemia: a randomized double-blind placebo-controlled trial.

Data from small clinical trials in the United States and India suggest zinc supplementation reduces infection in adolescents and adults with sickle cell anemia (SCA), but no studies of zinc supplementation for infection prevention have been conducted in children with SCA living in Africa. We conducted a randomized double-blind placebo-controlled trial to assess zinc supplementation for prevention of severe or invasive infections in Ugandan children 1.00-4.99 years with SCA. Of 252 enrolled participants, 124 were assigned zinc (10 mg) and 126 assigned placebo once daily for 12 months. The primary outcome was incidence of protocol-defined severe or invasive infections. Infection incidence did not differ between treatment arms (282 vs. 270 severe or invasive infections per 100 person-years, respectively, incidence rate ratio of 1.04 [95% confidence interval (CI), 0.81, 1.32, p=0.78]), adjusting for hydroxyurea treatment. There was also no difference between treatment arms in incidence of serious adverse events or SCA-related events. Children receiving zinc had increased serum levels after 12-months, but at study exit, 41% remained zinc deficient (<65 µg/dL). In post-hoc analysis, occurrence of stroke or death was lower in the zinc treatment arm (adjusted hazard ratio (95% CI), 0.22 (0.05, 1.00); p=0.05). Daily 10 mg zinc supplementation for 12 months did not prevent severe or invasive infections in Ugandan children with SCA, but many supplemented children remained zinc deficient. Optimal zinc dosing and the role of zinc in preventing stroke or death in SCA warrant further investigation. This trial was registered at clinicaltrials.gov as #NCT03528434.

Cellular Zinc Deficiency Impairs Heme Biosynthesis in Developing Erythroid Progenitors.

Anemia is the most prevalent nutrition-related disorder worldwide. Zinc is an essential trace element for various biological processes in the body, and zinc deficiency has been associated with anemia in humans. However, the molecular mechanisms by which zinc availability alters red blood cell development remain uncertain. The present study identifies the essentiality of zinc during erythroid development, particularly for normal heme biosynthesis. G1E-ER4 mouse cells were used as an in vitro model of terminal erythroid differentiation, which featured elevated cellular zinc content by development. Restriction of zinc import compromised the rate of heme and α-globin production and, thus, the hemoglobinization of the erythroid progenitors. Heme is synthesized by the incorporation of iron into protoporphyrin. The lower heme production under zinc restriction was not due to changes in iron but was attributable to less porphyrin synthesis. The requirement of adequate zinc for erythroid heme metabolism was confirmed in another erythropoietic cell model, MEL-DS19. Additionally, we found that a conventional marker of iron deficiency anemia, the ZnPP-to-heme ratio, responded to zinc restriction differently from iron deficiency. Collectively, our findings define zinc as an essential nutrient integral to erythroid heme biosynthesis and, thus, a potential therapeutic target for treating anemia and other erythrocyte-related disorders.

COVID-19 Alcoholic Cirrhosis and Non-Alcoholic Steatohepatitis Cirrhosis Outcomes among Hospitalized Patients in the United States: Insight from National Inpatient Sample Database.

Patients with co-morbidities like cirrhosis are at risk of worse outcome from COVID-19 infection. Given limited prior studies, we evaluated outcomes associated with COVID-19 infection in alcoholic and non-alcoholic steatohepatitis cirrhotic (CC+) versus cirrhotic without COVID-19 (CC−). We performed retrospective analysis of 822,604 patients including 28,610 COVID-19 patients from the National Inpatient Sample database with alcoholic and NASH cirrhosis enrolled between 1 January 2020 to 31 December 2020, with univariate and multivariate regression analyses. Primary outcome was mortality and secondary outcomes was mechanical ventilation, vasopressor use, length of stay, hospitalization expense and predictors of mortality. In-hospital mortality was three time higher in the CC+ group compared to those in the CC− group(18.6% vs. 5.96%, p < 0.001, adjusted odds ratio (OR)3.39 (95% 3.08−3.74 CI). Hospitalization was more likely for underrepresented racial and ethnic groups with COVID-19 and cirrhosis. CC+ group had over twice the rates of mechanical ventilation (19.92% vs. 9.07%, adjusted OR 2.71 2.71 (95% 2.51−2.93 CI)),1.7 times likelihood of receiving vasopressors (4.12% vs. 2.45%, p < 0.001, adjusted OR 1.71 (95% CI 1.46−2.01). COVID-19 is associated with increased mortality in patients with alcoholic and NASH cirrhosis, and patients with alcoholic cirrhosis and COVID-19 have a slightly higher mortality compared to NASH cirrhosis.

NCOA4 Regulates Iron Recycling and Responds to Hepcidin Activity and Lipopolysaccharide in Macrophages.

Macrophages, via erythrophagocytosis, recycle iron from effete erythrocytes to newly developing red blood cells. Conversion of potentially cytotoxic levels of iron from its heme into nonheme form during iron recycling is safely accomplished via coordinated regulations of cellular iron transport and homeostasis. Herein, we demonstrate the roles and regulation of NCOA4 (nuclear receptor coactivator 4)-mediated ferritinophagy in macrophages after erythrophagocytosis using the mouse macrophage cell line J774 cells. Ferritin in J774 cells increased with the rise of nonheme iron by erythrocyte ingestion and declined when total cellular iron contents subsequently decreased. NCOA4, a selective autophagic cargo receptor for ferritin, was responsible for the control of cellular ferritin and total iron contents at the later stage of erythrophagocytosis. A hepcidin analog, which limits the flux of iron through iron-recycling by inhibiting iron export at the plasma membrane, repressed NCOA4 expression and led to accumulation of ferritin in the mouse macrophages. Transcriptome analyses revealed a functional association of immune response with NCOA4-dependent gene expressions, and we confirmed repression of Ncoa4 by lipopolysaccharide (LPS) in J774 cells and the spleen of mice. Collectively, our studies indicate that NCOA4 facilitates cellular ferritin turnover and the release of iron by macrophages after erythrophagocytosis and functions as a regulatory target for molecular signals of systemic iron overload and inflammation. These identify macrophage NCOA4 as a potential therapeutic target for disorders of systemic iron dysregulation, including anemia of inflammation and hemochromatosis.

Extracorporeal Liver Support: An Updated Review of Mechanisms and Current Literature.

Introduction: Acute liver failure is a cause of major mortality in the United States. Although the liver possesses regenerative capabilities, liver transplantation is the mainstay of treating acute liver failure. This modality is associated with many financial and logistic challenges. In this regard, Extracorporeal Liver Support (ECLS) might help in reducing mortality as well as bridge a patient to liver transplant. In some cases, the sequelae of liver failure such as hepatic encephalopathy and multi-organ failure can be postponed long enough for the native liver to self-recover function. With this rationale, we sought to describe the mechanism of various ECLS modalities, provide an overview of the current evidence regarding its use and to highlight future advancements that could overcome hindrances in its use. Methods: A scoping review was performed using PubMed and other databases from 1990 to 2020 with the keywords: 'extracorporeal liver support', 'acute liver failure', 'acute on chronic liver failure', 'albumin dialysis', 'artificial' and 'bioartificial'. Results and conclusions: ECLS has shown significant improvements in bilirubin and urea levels. Various forms of ECLS might also reduce mortality due to liver failure. However, many complications, such as hypotension, anemia, bleeding issues, sepsis, can be anticipated. There are a few barriers to mainstream use of ECLS, such as specific design requirements and high cost that reduce the overall utility of this modality in a small group of liver transplant candidates. Furthermore, a multidisciplinary team approach is required to supervise ECLS, a luxury only available at major academic hospitals. Some advancements for overcoming these barriers include investigation of new scaffolding systems. In order to expand the usage of ECLS, clinical trials focusing on a comparison of different modalities of ECLS with renal replacement therapy in patients with liver failure should be promoted.

HYL1-CLEAVAGE SUBTILASE 1 (HCS1) suppresses miRNA biogenesis in response to light-to-dark transition.

The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1K154A mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway.

Digital Rectal Exam in the Acute Hospital Setting: Bridging Patient Experience and the Physician Perspective.

The digital rectal examination is one of the key physical examination tools used in the assessment of gastrointestinal bleed, different rectal diseases and prostate disease. It is an invasive diagnostic test that has a significant level of patient anxiety and discomfort involved. Despite its many diagnostic utilities this exam has been vastly underutilised due to many limiting factors including lack of physician confidence with this bedside physical maneuver. This review includes patient's point of view and providers perspective on digital rectal examination in the inpatient hospital setting. Some of the contributors to negative patient experience include opposite gender of the physician performing the procedure, lack of procedural awareness and expectations and repeat examinations due to improper electronic health care record charting. A better understanding of the limitations and constraints involved from both the patient and physician perspective can help improve patient experience and overall clinical outcomes.

The Causal Effects of Blood Iron and Copper on Lipid Metabolism Diseases: Evidence from Phenome-Wide Mendelian Randomization Study.

Blood levels of iron and copper, even within their normal ranges, have been associated with a wide range of clinical outcomes. The available epidemiological evidence for these associations is often inconsistent and suffers from confounding and reverse causation. This study aims to examine the causal clinical effects of blood iron and copper with Mendelian randomization (MR) analyses. Genetic instruments for the blood levels of iron and copper were curated from existing genome-wide association studies. Candidate clinical outcomes were identified based on a phenome-wide association study (PheWAS) between these genetic instruments and a wide range of phenotypes in 310,999 unrelated individuals of European ancestry from the UK Biobank. All signals passing stringent correction for multiple testing were followed by MR analyses, with replication in independent data sources where possible. We found that genetically predicted higher blood levels of iron and copper are both associated with lower risks of iron deficiency anemia (odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.67-0.85, p = 1.90 × 10-6 for iron; OR = 0.88, 95% CI: 0.78-0.98, p = 0.032 for copper), lipid metabolism disorders, and its two subcategories, hyperlipidemia (OR = 0.90, 95% CI: 0.85-0.96, p = 6.44 × 10-4; OR = 0.92, 95% CI: 0.87-0.98, p = 5.51 × 10-3) and hypercholesterolemia (OR = 0.90, 95% CI: 0.84-0.95, p = 5.34 × 10-4; OR = 0.93, 95% CI: 0.89-0.99, p = 0.022). Consistently, they are also associated with lower blood levels of total cholesterol and low-density lipoprotein cholesterol. Multiple sensitivity tests were applied to assess the presence of pleiotropy and the robustness of causal estimates. Regardless of the approaches, consistent evidence was obtained. Moreover, the unique clinical effects of each blood mineral were identified. Notably, genetically predicated higher blood iron is associated with an enhanced risk of varicose veins (OR = 1.28, 95% CI: 1.15-1.42, p = 4.34 × 10-6), while blood copper is positively associated with the risk of osteoarthrosis (OR = 1.07, 95% CI: 1.02-1.13, p = 0.010). Sex-stratified MR analysis further revealed some degree of sex differences in their clinical effects. Our comparative PheWAS-MR study of iron and copper comprehensively characterized their shared and unique clinical effects, highlighting their potential causal roles in hyperlipidemia and hypercholesterolemia. Given the modifiable nature of blood mineral status and the potential for clinical intervention, these findings warrant further investigation.

Light Triggers the miRNA-Biogenetic Inconsistency for De-etiolated Seedling Survivability in Arabidopsis thaliana.

The shift of dark-grown seedlings into light causes enormous transcriptome changes followed by a dramatic developmental transition. Here, we show that microRNA (miRNA) biogenesis also undergoes regulatory changes during de-etiolation. Etiolated seedlings maintain low levels of primary miRNAs (pri-miRNAs) and miRNA processing core proteins, such as Dicer-like 1, SERRATE, and HYPONASTIC LEAVES 1, whereas during de-etiolation both pri-miRNAs and the processing components accumulate to high levels. However, the levels of most miRNAs do not notably increase in response to light. To reconcile this inconsistency, we demonstrated that an unknown suppressor decreases miRNA-processing activity and light-induced SMALL RNA DEGRADING NUCLEASE 1 shortens the half-life of several miRNAs in de-etiolated seedlings. Taken together, these data suggest a novel mechanism, miRNA-biogenetic inconsistency, which accounts for the intricacy of miRNA biogenesis during de-etiolation. This mechanism is essential for the survival of de-etiolated seedlings after long-term skotomorphogenesis and their optimal adaptation to ever-changing light conditions.

Classification of barley U-box E3 ligases and their expression patterns in response to drought and pathogen stresses.

BACKGROUND: Controlled turnover of proteins as mediated by the ubiquitin proteasome system (UPS) is an important element in plant defense against environmental and pathogen stresses. E3 ligases play a central role in subjecting proteins to hydrolysis by the UPS. Recently, it has been demonstrated that a specific class of E3 ligases termed the U-box ligases are directly associated with the defense mechanisms against abiotic and biotic stresses in several plants. However, no studies on U-box E3 ligases have been performed in one of the important staple crops, barley. RESULTS: In this study, we identified 67 putative U-box E3 ligases from the barley genome and expressed sequence tags (ESTs). Similar to Arabidopsis and rice U-box E3 ligases, most of barley U-box E3 ligases possess evolutionary well-conserved domain organizations. Based on the domain compositions and arrangements, the barley U-box proteins were classified into eight different classes. Along with this new classification, we refined the previously reported classifications of U-box E3 ligase genes in Arabidopsis and rice. Furthermore, we investigated the expression profile of 67 U-box E3 ligase genes in response to drought stress and pathogen infection. We observed that many U-box E3 ligase genes were specifically up-and-down regulated by drought stress or by fungal infection, implying their possible roles of some U-box E3 ligase genes in the stress responses. CONCLUSION: This study reports the classification of U-box E3 ligases in barley and their expression profiles against drought stress and pathogen infection. Therefore, the classification and expression profiling of barley U-box genes can be used as a platform to functionally define the stress-related E3 ligases in barley.

Low binding affinity and reduced complement-dependent cell death efficacy of ofatumumab produced using a plant system (Nicotiana benthamiana L.).

The plant protein production system is a platform that can not only reduce production costs but also produce monoclonal antibodies that do not have the risk of residual proteins from the host. However, due to the difference between post-translational processes in plants and animals, there may be a modification in the Fab region of the monoclonal antibody produced in the plant; thus, it is necessary to compare the antigen affinity of this antibody with that of the prototype. In this study, ofatumumab, a fully human anti-CD20 IgG1κ monoclonal antibody used for its non-cross resistance to rituximab, was expressed in Nicotiana benthamiana, and its affinities and efficacies were compared with those of native ofatumumab produced from CHO cells. Two forms of plant ofatumumab (with or without HDEL-tag) were generated and their production yields were compared. The HDEL-tagged ofatumumab was more expressed in plants than the form without HDEL-tag. The specificity of the target recognition of plant-derived ofatumumab was confirmed by mCherry-CD20-expressing HEK cells via immuno-staining, and the capping of CD20 after ofatumumab binding was also confirmed using Ramos B cells. In the functional equivalence tests, the binding affinities and complement-dependent cell cytotoxicity efficacy of plant-ofatumumab-HDEL and plant-ofatumumab without HDEL were significantly reduced compared to those of CHO-derived ofatumumab. Therefore, we suggest that although ofatumumab is not a good candidate as a template for plant-derived monoclonal antibodies because of its decreased affinity when produced in plants, it is an interesting target to study the differences between post-translational modifications in mammals and plants.

Study on the copper(II)-doped MIL-101(Cr) and its performance in VOCs adsorption.

The metal-organic framework (MOF) materials, MIL-101(Cr), and copper-doped MIL-101(Cr) (Cu@MIL-101(Cr)) were prepared through hydrothermal method and were used to remove volatile organic compounds (VOCs) in this study. Morphological characterization demonstrated that MIL-101(Cr) and Cu-3@MIL-101(Cr) were octahedral crystal, with specific surface area of 3367 and 2518 m2/g, respectively. The results of XRD, TG, and FTIR showed that the copper doping procedure would not alter the skeleton structure, but it would affect the crystallinity and thermal stability of MIL-101(Cr). Besides, MIL-101(Cr) and Cu-3@MIL-101(Cr) displayed good removal efficiencies on benzene sorption, and the maximum sorption capacity was 103.4 and 114.4 mg/g, respectively. In competitive adsorptions, the order of adsorption priority on Cu-3@MIL-101(Cr) was as follows: ethylbenzene > toluene > benzene. Hence, it could be concluded that MIL-101(Cr) and copper-doped MIL-101(Cr) demonstrated good performance in VOCs adsorption and showed a promising potential for large-scale applications in the removal of VOCs. Graphical abstract ᅟ.

A Quick HYL1-Dependent Reactivation of MicroRNA Production Is Required for a Proper Developmental Response after Extended Periods of Light Deprivation.

Light is the most influential environmental stimulus for plant growth. In response to deficient light, plants reprogram their development to adjust their growth in search for a light source. A fine reprogramming of gene expression orchestrates this adaptive trait. Here we show that plants alter microRNA (miRNA) biogenesis in response to light transition. When plants suffer an unusual extended period of light deprivation, the miRNA biogenesis factor HYPONASTIC LEAVES 1 (HYL1) is degraded but an inactive pool of phosphorylated protein remains stable inside the nucleus. Degradation of HYL1 leads to the release of gene silencing, triggering a proper response to dark and shade. Upon light restoration, a quick dephosphorylation of HYL1 leads to the reactivation of miRNA biogenesis and a switch toward a developmental program that maximizes the light uptake. Our findings define a unique and fast regulatory mechanism controlling the plant silencing machinery during plant light response.

Ferritin iron regulators, PCBP1 and NCOA4, respond to cellular iron status in developing red cells.

Developing red blood cells exhibit multiple, redundant systems for regulating and coordinating the uptake of iron, the synthesis of heme, and the formation of hemoglobin during terminal differentiation. We recently described the roles of poly rC-binding protein (PCBP1) and nuclear coactivator 4 (NCOA4) in mediating the flux of iron through ferritin in developing erythroid cells, with PCBP1, an iron chaperone, delivering iron to ferritin and NCOA4, an autophagic cargo receptor, directing ferritin to the lysosome for degradation and iron release. Ferritin iron flux is critical, as mice lacking these factors develop microcytic anemia. Here we report that these processes are regulated by cellular iron levels in a murine model of ex vivo terminal differentiation. PCBP1 delivers iron to ferritin via a direct protein-protein interaction. This interaction is developmentally regulated, enhanced by iron deprivation, and inhibited by iron excess, both in developing cells and in vitro. NCOA4 activity also exhibited developmental regulation and regulation by cellular iron levels. Excess iron uptake during differentiation triggered lysosomal degradation of NCOA4, which was dependent on the E3 ubiquitin ligase HERC2. Thus, developing red blood cells express a series of proteins that both mediate and regulate the flux of iron to the mitochondria.

MPSR1 is a cytoplasmic PQC E3 ligase for eliminating emergent misfolded proteins in Arabidopsis thaliana.

Ubiquitin E3 ligases are crucial for eliminating misfolded proteins before they form cytotoxic aggregates that threaten cell fitness and survival. However, it remains unclear how emerging misfolded proteins in the cytoplasm can be selectively recognized and eliminated by E3 ligases in plants. We found that Misfolded Protein Sensing RING E3 ligase 1 (MPSR1) is an indispensable E3 ligase required for plant survival after protein-damaging stress. Under no stress, MPSR1 is prone to rapid degradation by the 26S proteasome, concealing its protein quality control (PQC) E3 ligase activity. Upon proteotoxic stress, MPSR1 directly senses incipient misfolded proteins and tethers ubiquitins for subsequent degradation. Furthermore, MPSR1 sustains the structural integrity of the proteasome complex at the initial stage of proteotoxic stress. Here, we suggest that the MPSR1 pathway is a constitutive mechanism for proteostasis under protein-damaging stress, as a front-line surveillance system in the cytoplasm.

Corrosion resistance and bioactivity enhancement of MAO coated Mg alloy depending on the time of hydrothermal treatment in Ca-EDTA solution.

In this study, a two-step surface treatment was developed to restrain the rapid primary degradation of a biodegradable Mg alloy and to improve their biocompatibility. Micro arc oxidation (MAO) coating was performed in alkaline electrolytes such as 1.0 M NaOH with 0.1 M glycerol and 0.1 M Na3PO4. Hydrothermal treatment was performed in 0.1 M Ca-EDTA (C10H12CaN2Na2O8) and 0.5 M NaOH solution at 90 °C for different times (6, 12, 24, and 48 h). The film morphology and chemical properties were evaluated by XRD and FE-SEM. The electrochemical and corrosion behaviors were examined in the simulated body fluid, and cytotoxicity was assessed using MC3T3-E1 cells. After MAO coating, an oxide layer containing [Formula: see text] formed on the surface. During the hydrothermal treatment in Ca-EDTA solution, calcium phosphate and Mg(OH)2 were produced via a reaction between [Formula: see text] on the surface and Ca2+ in solution. The layer with ceramics and oxides was grown on the surface with increasing hydrothermal treatment time, and improved the surface corrosion resistance. The 24 h hydrothermal-treated group showed the lowest immersion corrosion rate and high cell viability. Therefore, this treatment was the most favorable surface modification for improving the initial corrosion resistance and bioactivity of the biodegradable Mg alloy.

RING E3 ligases: key regulatory elements are involved in abiotic stress responses in plants.

Plants are constantly exposed to a variety of abiotic stresses, such as drought, heat, cold, flood, and salinity. To survive under such unfavorable conditions, plants have evolutionarily developed their own resistant-mechanisms. For several decades, many studies have clarified specific stress response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways. In the UPS, many E3 ligases play key roles in recognizing and tethering poly-ubiquitins on target proteins for subsequent degradation by the 26S proteasome. Here we discuss the roles of RING ligases that have been defined in related to abiotic stress responses in plants. [BMB Reports 2017; 50(8): 393-400].