Reducing mental health emergency visits: population-level strategies from participatory modelling.

BACKGROUND: Emergency departments (EDs) are often the front door for urgent mental health care, especially when demand exceeds capacity. Long waits in EDs exert strain on hospital resources and worsen distress for individuals experiencing a mental health crisis. We used as a test case the Australian Capital Territory (ACT), with a population surge of over 27% across 2011-2021 and a lagging increase in mental health care capacity, to evaluate population-based approaches to reduce mental health-related ED presentations. METHODS: We developed a system dynamics model for the ACT region using a participatory approach involving local stakeholders, including health planners, health providers and young people with lived experience of mental health disorders. Outcomes were projected over 2023-2032 for youth (aged 15-24) and for the general population. RESULTS: Improving the overall mental health care system through strategies such as doubling the annual capacity growth rate of mental health services or leveraging digital technologies for triage and care coordination is projected to decrease youth mental health-related ED visits by 4.3% and 4.8% respectively. Implementation of mobile crisis response teams (consisting of a mental health nurse accompanying police or ambulance officers) is projected to reduce youth mental health-related ED visits by 10.2% by de-escalating some emergency situations and directly transferring selected individuals to community mental health centres. Other effective interventions include limiting re-presentations to ED by screening for suicide risk and following up with calls post-discharge (6.4% reduction), and limiting presentations of frequent users of ED by providing psychosocial education to families of people with schizophrenia (5.1% reduction). Finally, combining these five approaches is projected to reduce youth mental health-related ED presentations by 26.6% by the end of 2032. CONCLUSIONS: Policies to decrease youth mental health-related ED presentations should not be limited to increasing mental health care capacity, but also include structural reforms.

Non-thermal atmospheric pressure plasma induces selective cancer cell apoptosis by modulating redox homeostasis.

BACKGROUND: Anticancer treatments aim to selectively target cancer cells without harming normal cells. While non-thermal atmospheric pressure plasma (NTAPP) has shown anticancer potential across various studies, the mechanisms behind its selective action on cancer cells remain inadequately understood. This study explores the mechanism of NTAPP-induced selective cell death and assesses its application in cancer therapy. METHODS: We treated HT1080 fibrosarcoma cells with NTAPP and assessed the intracellular levels of mitochondria-derived reactive oxygen species (ROS), mitochondrial function, and cell death mechanisms. We employed N-acetylcysteine to investigate ROS's role in NTAPP-induced cell death. Additionally, single-cell RNA sequencing was used to compare gene expression in NTAPP-treated HT1080 cells and human normal fibroblasts (NF). Western blotting and immunofluorescence staining examined the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), a key antioxidant gene transcription factor. We also evaluated autophagy activity through fluorescence staining and transmission electron microscopy. RESULTS: NTAPP treatment increased ROS levels and induced mitochondrial dysfunction, leading to apoptosis in HT1080 cells. The involvement of ROS in selective cancer cell death was confirmed by N-acetylcysteine treatment. Distinct gene expression patterns were observed between NTAPP-treated NF and HT1080 cells, with NF showing upregulated antioxidant gene expression. Notably, NRF2 expression and nuclear translocation increased in NF but not in HT1080 cells. Furthermore, autophagy activity was significantly higher in normal cells compared to cancer cells. CONCLUSIONS: Our study demonstrates that NTAPP induces selective cell death in fibrosarcoma cells through the downregulation of the NRF2-induced ROS scavenger system and inhibition of autophagy. These findings suggest NTAPP's potential as a cancer therapy that minimizes damage to normal cells while effectively targeting cancer cells.

CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease.

In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups. We validated our findings with independent ADAD as well as sporadic AD datasets and employed machine learning to develop and validate predictive models. Our study identified 137 proteins with distinct trajectories between MCs and NCs, including eight that changed before traditional AD biomarkers. These proteins are grouped into three stages: early stage (stress response, glutamate metabolism, neuron mitochondrial damage), middle stage (neuronal death, apoptosis), and late presymptomatic stage (microglial changes, cell communication). The predictive model revealed a six-protein subset that more effectively differentiated MCs from NCs, compared with conventional biomarkers.

Predictors for COVID-19-Specific and Non-COVID-19-Specific Deaths: A Cohort Study in Taiwan.

Predictors for coronavirus disease 2019 (COVID-19)-specific and non-COVID-19-specific deaths have not been extensively studied. This cohort study in Taiwan investigated predictors for COVID-19-specific and non-COVID-19-specific deaths among hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. From January to July 2022, 2196 COVID-19 patients at Taipei City Hospital were consecutively recruited in this cohort study. Among the 175 deceased COVID-19 patients, 147 (84.0%) and 28 (16.0%) had COVID-19-specific and non-COVID-19-specific deaths, respectively. After controlling for other covariates, multinomial logistic regressions showed that age ≥ 65 was significantly associated with higher risks for both COVID-19-specific, adjusted odds ratio (AOR) = 6.21; 95% confidence interval (CI) [3.12, 12.35]; and non-COVID-19-specific deaths (AOR = 6.06; 95% CI [1.34, 27.34]). Fully vaccinated individuals (AOR = 0.50; 95% CI [0.33, 0.74]) and Paxlovid recipients (AOR = 0.45; 95% CI [0.20, 0.98]) had lower COVID-19-specific death risks, while comorbid cancer or end-stage renal disease patients faced higher risks of non-COVID-19-specific deaths. Our study findings suggest that vaccination and Paxlovid treatment are crucial for reducing SARS-CoV-2-specific mortalities, while comorbid patients need careful monitoring to reduce non-COVID-19-specific deaths.

A novel liquid plasma derivative inhibits melanogenesis through upregulation of Nrf2.

Non-thermal plasma (NTP) is an emerging technology with extensive applications in biomedicine, including treatment of abnormal pigmentation. However, very few studies have investigated how plasma induces anti-melanogenesis. Here, liquid plasma was prepared by treating an NTP jet with helium and oxygen (as carrier gases) for 15 min in serum-free culture media. In the zebrafish model, pigmentation ratio was observed with or without liquid plasma. The anti-melanogenic effect of liquid plasma was evaluated in human melanocytes by assessing the expression of melanogenesis-related genes using western blotting, RT-PCR, and immunohistochemistry. Liquid plasma reduced pigmentation in the zebrafish model and inhibited melanin synthesis in primary human melanocytes. Intracellular reactive oxygen species levels decreased and Nrf2 expression increased in liquid plasma-treated melanocytes. Liquid plasma affected microphthalmia-associated transcription factor (MITF) and tyrosinase mRNA and protein levels, tyrosinase activity, and melanin content. Considering the role of Wnt/ß-catenin and PI3K/Akt pathways in melanogenesis, the effect of liquid plasma on this pathway was determined; liquid plasma decreased active ß-catenin, LEF1/TCF4, MITF, and tyrosinase levels in a time-dependent manner and inhibited the nuclear translocation of ß-catenin. This inhibition subsequently suppressed melanogenesis by downregulating MITF and tyrosinase. These results suggest that liquid plasma may be used for treating pigmentary disorders.

Early-onset Adjacent Vertebral Fractures after Balloon Kyphoplasty and SpineJack® Kyphoplasty for the Management of Single-level Thoracolumbar Vertebral Compression Fractures.

OBJECTIVE: To evaluate the risk factors contributing to early-onset adjacent level fractures (ALFs) occurring within 1 month following either balloon kyphoplasty (BKP) or SpineJack® kyphoplasty (SJ) for the treatment of thoracolumbar vertebral compression fractures (TLVCFs). MATERIALS AND METHODS: This retrospective analysis enrolled patients with single-level TLVCFs (T11-L2) who underwent either BKP or SJ between July 2013 and June 2019. We recorded the ALF occurrences within 1 month. Age, osteoporosis, severity and shape of TLVCFs, and surgical type were compared between patients with and without early-onset ALFs. RESULTS: Altogether, 106 TLVCF patients were enrolled, comprising 64 BKP and 42 SJ cases. We observed 19 early-onset ALFs, with 9 and 10 cases in the BKP and SJ, respectively. Patients with early-onset ALFs have significantly more severe TLCVFs (severe versus mild, 25% versus 0%, p = 0.055) and wedge-shaped TLVCFs (26.47% versus 2.63%, p = 0.002) and older age (81.05 versus 73.34 years, p < 0.001) and kyphoplasty performed within 1 month are risk factors of early-onset ALFs (26.92% versus 9.26%, p = 0.018). Univariable analysis showed that kyphoplasty timing within 1 month (odds ratio [OR]: 0.193, p = 0.008), wedge-shaped TLVCFs (OR: 5.358, p = 0.036), and advanced age (OR: 1.119, p = 0.001) are significant risk factors of early-onset ALFs. CONCLUSIONS: The occurrence rate of early-onset ALFs between BKP or SJ techniques in treating TLVCFs does not differ. Preoperative wedge-shaped TLVCFs, advanced age, and early treatment within 1 month are the risk factors of early-onset ALFs following kyphoplasty for TLVCFs.

Ovarian Clear Cell Carcinoma: An Endometriosis-Associated Cancer with Therapeutic Challenges.

Ovarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer with distinct pathological features, molecular profiles, and biological functions. OCCC has high incidence rates in East Asia compared to the Western hemisphere and Europe and is associated with endometriosis. With its relative resistance to conventional treatment regimens and the worst stage-adjusted prognosis among ovarian cancer subtypes, there is an urgent need to optimize therapeutic options and to improve patient outcomes. To achieve this goal, better patient stratification strategies are required. These strategies could derive from comprehensive and in-depth multidimensional analysis of tumor heterogeneity. Understanding intertumor heterogeneity could assist us in stratifying OCCC patients based on features that are prognostic or predictive. Recent genomic, epigenomic, and transcriptomic profiling analyses allow us to provide an integrative perspective on the diverse heterogeneity in OCCC that could pave the way for novel translational research and clinical development in the future.

Developing a plant microbial fuel cell by planting water spinach in a hanging-submerged plant pot system.

To plant crops (especially dry crops such as water spinach) with concomitant electricity recovery, a hanging-submerged-plant-pot system (HSPP) is developed. The HSPP consists of a soil pot (anodic) partially submerged under the water surface of a cathode tank. The microbial communities changed with conditions were also investigated. It was found that with chemical fertilizers the closed-circuit voltage (CCV, with 1 kΩ) was stable (approximately 250 mV) within 28 d; however, without fertilizer, the water spinach could adjust to the environment to obtain a better power output (approximately 3 mW m-2) at day 28. The microbial-community analyses revealed that the Pseudomonas sp. was the only exoeletrogens found in the anode pots. Using a secondary design of HSPP, for a better water-level adjustment, the maximum power output of each plant was found to be approximately 27.1 mW m-2. During operation, high temperature resulted in low oxygen solubility, and low CCV as well. At this time, it is yet to be concluded whether the submerged water level significantly affects electricity generation.

Ubiquitin-Proteasome System in the Different Stages of Dominantly Inherited Alzheimer's Disease.

This study explored the role of the ubiquitin-proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining changes in cerebrospinal fluid (CSF) levels of UPS proteins along with disease progression, AD imaging biomarkers (PiB PET, tau PET), neurodegeneration imaging measures (MRI, FDG PET), and Clinical Dementia Rating® (CDR®). Using the SOMAscan assay, we detected subtle increases in specific ubiquitin enzymes associated with proteostasis in mutation carriers (MCs) up to two decades before the estimated symptom onset. This was followed by more pronounced elevations of UPS-activating enzymes, including E2 and E3 proteins, and ubiquitin-related modifiers. Our findings also demonstrated consistent correlations between UPS proteins and CSF biomarkers such as Aß42/40 ratio, total tau, various phosphorylated tau species to total tau ratios (ptau181/T181, ptauT205/T205, ptauS202/S202, ptauT217/T217), and MTBR-tau243, alongside Neurofilament light chain (NfL) and the CDR®. Notably, a positive association was observed with imaging markers (PiB PET, tau PET) and a negative correlation with markers of neurodegeneration (FDG PET, MRI), highlighting a significant link between UPS dysregulation and neurodegenerative processes. The correlations suggest that the increase in multiple UPS proteins with rising tau levels and tau-tangle associated markers, indicating a potential role for the UPS in relation to misfolded tau/neurofibrillary tangles (NFTs) and symptom onset. These findings indicate that elevated CSF UPS proteins in DIAD MCs could serve as early indicators of disease progression and suggest a link between UPS dysregulation and amyloid plaque, tau tangles formation, implicating the UPS as a potential therapeutic target in AD pathogenesis.

Developmental Impacts of Early Sensory Patterns on School-Age Adaptive, Maladaptive, and Participation Outcomes in Autistic and Non-autistic Children.

Early sensory differences may cascade into later social-communication difficulties in autism, yet their impacts on broader functional outcomes have remained understudied. This study aimed to conduct a comprehensive investigation into the longitudinal impacts of sensory patterns, including sensory hyperresponsiveness, hyporesponsiveness, and sensory repetitions/seeking behavior, on various school-age outcome domains among a community sample of children with autistic and non-autistic conditions. We prospectively followed 1,517 children with caregiver-reported sensory questionnaires across three timepoints from infancy to school age. A subsample (n = 389; 88 with reported autism diagnosis/concerns) was further assessed with adaptive, maladaptive and participation outcome measures at age 6-7. Structural equation modeling approaches were used to evaluate the multivariate associations between latent growth parameters (i.e., intercepts and slopes) of sensory patterns and school-age outcomes. Increasing sensory hyperresponsiveness was directly associated with poorer adaptive/maladaptive outcomes and indirectly with lower participation in activities with higher functional demands across settings at school age. Elevated sensory hyporesponsiveness was associated with lower adaptive functioning, more externalizing problems, and lower classroom participation. Trajectories of sensory patterns accounted for more unique variances in adaptive functioning and participation in daily life settings with higher functional and environmental demands among autistic children compared to their non-autistic peers.

European and African-specific plasma protein-QTL and metabolite-QTL analyses identify ancestry-specific T2D effector proteins and metabolites.

Initially focused on the European population, multiple genome-wide association studies (GWAS) of complex diseases, such as type-2 diabetes (T2D), have now extended to other populations. However, to date, few ancestry-matched omics datasets have been generated or further integrated with the disease GWAS to nominate the key genes and/or molecular traits underlying the disease risk loci. In this study, we generated and integrated plasma proteomics and metabolomics with array-based genotype datasets of European (EUR) and African (AFR) ancestries to identify ancestry-specific muti-omics quantitative trait loci (QTLs). We further applied these QTLs to ancestry-stratified T2D risk to pinpoint key proteins and metabolites underlying the disease-associated genetic loci. We nominated five proteins and four metabolites in the European group and one protein and one metabolite in the African group to be part of the molecular pathways of T2D risk in an ancestry-stratified manner. Our study demonstrates the integration of genetic and omic studies of different ancestries can be used to identify distinct effector molecular traits underlying the same disease across diverse populations. Specifically, in the AFR proteomic findings on T2D, we prioritized the protein QSOX2; while in the AFR metabolomic findings, we pinpointed the metabolite GlcNAc sulfate conjugate of C21H34O2 steroid. Neither of these findings overlapped with the corresponding EUR results.

Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan.

BACKGROUND: This cohort study determines the predictors for cause-specific and timing of deaths in patients with COVID-19 in Taiwan. METHODS: Patients with laboratory-confirmed COVID-19 admitted to Taipei City Hospital from January 1 to July 31, 2022, were recruited in this cohort. All patients were followed up until death, discharge from the hospital, or August 31, 2022. Early deaths within the first 2 weeks were recorded, and the cause of death was confirmed by the death certificate database of Taiwan. Predictors of cause-specific and timing of deaths of patients with COVID-19 were determined using multinomial Cox proportional hazards regression analysis. RESULTS: Of the 195 (8.0%) patients who died during hospitalization, 147 (84.0%) had COVID-19-specific deaths. Moreover, 54.9% of the deceased patients had early death. After controlling for other covariates, patients aged ≥ 65 years had a higher risk of COVID-19-specific, non-COVID-19-specific, early, and late deaths [adjusted hazards ratio (AHR): 3.85, 6.45, 3.33, and 6.57; 95% confidence interval (CI): 1.91-7.78, 1.17-35.68, 1.51-7.36, and 2.18-19.76, respectively]. Fully vaccinated patients had a lower risk of COVID-19-specific (AHR: 0.68; 95% CI: 0.47-0.98) and early deaths (AHR: 0.54; 95% CI: 0.35-0.84), whereas comorbid patients with chronic obstructive pulmonary disease had a higher risk of non-COVID-19-specific deaths (AHR: 5.43; 95% CI: 1.73-17.03). CONCLUSIONS: This study suggests that prioritizing COVID-19 vaccination and carefully monitoring comorbid patients during hospitalization can reduce the risk of COVID-19-specific and early deaths and non-COVID-19-specific mortalities, respectively.

Genomic analyses of intricate interaction of TE-lncRNA overlapping genes with miRNAs in human diseases.

BACKGROUND: Transposable elements (TEs) are known to be inserted into genome to create transcript isoforms or to generate long non-coding RNA (lncRNA) sequences. The insertion of TEs generates a gene protein sequence within the genome, but also provides a microRNA (miRNA) regulatory region. OBJECTIVE: To determine the effect of gene sequence changes caused by TE insertion on miRNA binding and to investigate the formation of an overlapping lncRNA that represses it. METHODS: The distribution of overlapping regions between exons and TE regions with lncRNA was examined using the Bedtools. miRNAs that can bind to those overlapping regions were identified through the miRDB web program. For TE-lncRNA overlapping genes, bioinformatic analysis was conducted using DAVID web database. Differential expression analysis was conducted using data from the GEO dataset and TCGA. RESULTS: Most TEs were distributed more frequently in untranslated regions than open reading frames. There were 30 annotated TE-lncRNA overlapping genes with same strand that could bind to the same miRNA. As a result of identifying the association between these 30 genes and diseases, TGFB2, FCGR2A, DCTN5, and IFI6 were associated with breast cancer, and HMGCS1, FRMD4A, EDNRB, and SNCA were associated with Alzheimer's disease. Analysis of the GEO and TCGA data showed that the relevant expression of miR-891a and miR-28, which bind to the TE overlapping region of DCTN5 and HMGCS1, decreased. CONCLUSION: This study indicates that the interaction between TE-lncRNA overlapping genes and miRNAs can affect disease progression.

Comparison of One-Year Outcome of Intravitreal Aflibercept with or without Photodynamic Therapy for Polypoidal Choroidal Vasculopathy.

Background and Objectives: Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods: This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results: The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions: The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.

Expanding the Spectral Responsivity of Photodetectors via the Integration of CdSe/ZnS Quantum Dots and MEH-PPV Polymer Composite.

This study investigates the energy transfer mechanism between the organic polymer poly(2-methoxy-5(2'-ethyl)heroxyphenylenevinylene) (MEH-PPV) and CdSe/ZnS core-shell quantum dots (CdSe/ZnS CSQDs). Additionally, a hybrid ZnO-based photodetector (PD) is fabricated using the composite of MEH-PPV and CdSe/ZnS CSQDs, aiming to gain deeper insights. The combination of MEH-PPV and CdSe/ZnS CSQDs facilitates a broad spectral response in PDs, spanning from the ultraviolet (UV) to the visible range. In particular, PDs with QDs in the composite demonstrate notably excellent photosensitivity to both ultraviolet (UV) light (365 nm) (~5 fold) and visible light (505 nm) (~3 fold).

Three-Dimensional Quantitative Analysis of Internal Limiting Membrane Peeling Related Structural Changes in Retinal Detachment Repair.

PURPOSE: To assess macular microstructural changes associated with internal limiting membrane peeling (ILMP) using 3-dimensional optical coherence tomography (3D-OCT) in primary macula-off rhegmatogenous retinal detachment (RRD) repairs with vitrectomy and silicone oil (SO) tamponade. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Setting: Institutional practice. PATIENT POPULATION: Patients who received primary RRD repair by a single experienced surgeon between January 2017 and December 2021. MAIN OUTCOME MEASURES: In the qualitative comparative analysis, the presence of macular changes among patients who underwent primary RRD repair with (21 eyes) or without ILMP (20 eyes) were observed. Subsequently, a detailed quantitative analysis of ILMP-related microstructural changes in 56 eyes using both 3D and 2D-OCT images were performed. RESULTS: In the qualitative comparative analysis, macular microstructural changes were observed in 95% of ILMP eyes and 5% of non-ILMP eyes (p < .001). In the quantitative analysis, 4 major macular microstructural changes were detected: dimple (75%), dissociated nerve fiber layer (DONFL) (55%), ILM peeling edge thinning (IPET) (64%), and temporal macular groove (TMG) (23%). Dimples (n = 251, average 4.5 ± 5.8 per eye) could be further classified into type I (confined to the inner plexiform layer [IPL]; 73%) and type II (beyond IPL, 27%). The average depth of the deepest dimples was 58 ± 18 µm. The extent of IPET was 6.0 ± 3.7 clock hours. The average length of TMG was 1.8 ± 0.4 mm. Comparing to unoperated fellow eyes, the eyes after ILMP showed decreased inner temporal over nasal retinal thickness ratio (0.86 ± 0.07 versus 0.96 ± 0.03, p < .001), shorter disc-fovea distance (4.61 ± 0.32 µm versus 4.78 ± 0.37 µm, p = .041), and wider retinal vein trajectories (c' = 2.48 ± 0.84 vs 3.39 ± 1.61, p = .002). CONCLUSIONS: Macular microstructural changes are common after ILMP in RRD repair, encompassing both focal changes (dimples, DONFL) and zonal changes (IPET, TMG). DONFL and dimples may be part of a continuum of findings stemming from the same mechanism. IPET and TMG are the results of macular tissue shift due to contracture of the optic disc and neurovascular bundle.

Spirobenzofuran Mitigates Ochratoxin A-Mediated Intestinal Adverse Effects in Pigs through Regulation of Beta Defensin 1.

Antimicrobial peptides (AMPs) function to extensively suppress various problematic factors and are considered a new alternative for improving livestock health and enhancing immunomodulation. In this study, we explored whether AMP regulation has positive influences on Ochratoxin A (OTA) exposure using a porcine intestinal epithelial cell line (IPEC-J2 cells). We constructed a beta-defensin 1 (DEFB1) expression vector and used it to transfection IPEC-J2 cells to construct AMP overexpression cell lines. The results showed that OTA induced cytotoxicity, decreased cell migration, and increased inflammatory markers mRNA in IPEC-J2 cells. In DEFB1 overexpressing cell lines, OTA-induced reduced cell migration and increased inflammatory markers mRNA were alleviated. Additionally, a natural product capable of inducing DEFB1 expression, which was selected through high-throughput screening, showed significant alleviation of cytotoxicity, cell migration, and inflammatory markers compared to OTA-treated IPEC-J2 cells. Our finding provides novel insights and clues for the porcine industry, which is affected by OTA exposure.

The single RRM domain-containing protein SARP1 is required for establishment of the separation zone in Arabidopsis.

Abscission is the shedding of plant organs in response to developmental and environmental cues. Abscission involves cell separation between two neighboring cell types, residuum cells (RECs) and secession cells (SECs) in the floral abscission zone (AZ) in Arabidopsis thaliana. However, the regulatory mechanisms behind the spatial determination that governs cell separation are largely unknown. The class I KNOTTED-like homeobox (KNOX) transcription factor BREVIPEDICELLUS (BP) negatively regulates AZ cell size and number in Arabidopsis. To identify new players participating in abscission, we performed a genetic screen by activation tagging a weak complementation line of bp-3. We identified the mutant ebp1 (enhancer of BP1) displaying delayed floral organ abscission. The ebp1 mutant showed a concaved surface in SECs and abnormally stacked cells on the top of RECs, in contrast to the precisely separated surface in the wild-type. Molecular and histological analyses revealed that the transcriptional programming during cell differentiation in the AZ is compromised in ebp1. The SECs of ebp1 have acquired REC-like properties, including cuticle formation and superoxide production. We show that SEPARATION AFFECTING RNA-BINDING PROTEIN1 (SARP1) is upregulated in ebp1 and plays a role in the establishment of the cell separation layer during floral organ abscission in Arabidopsis.

Association of Perinatal Cardiovascular Features with Angiotensin System Expressions in Maternal Preeclampsia.

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.