Putative Role Research Articles

CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells, pulmonary microvascular endothelial cells, and pericytes under hypoxia.

Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real-time polymerase chain reaction, Cell Counting Kit-8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA-432-5p (miR-432-5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR-433-3p in PMECs, and upregulate zinc finger AN1-type containing 5 (ZFAND5) expression by targeting miR-3613-5p in PCs. Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs, through the miR-433-3p/MXI1 axis in PMECs, and through the miR-3613-5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

#4127 MODULATION OF BLOOD PRESSURE THROUGH MICROBIOME EXCHANGE BETWEEN MILAN NORMOTENSIVE AND HYPERTENSIVE STRAINS OF RATS

Abstract Background and Aims Hypertension is one of the major health problems contributing to the development of cardiovascular diseases. In contrast to essential hypertension, which often displays complex pathogenesis due to multifactorial aetiology, several monogenic forms of hypertension are caused by mutations in genes associated with renal salt handling. Thus, studies on monogenic forms of hypertension could hold potential for novel therapeutic approaches for essential hypertension. Recently, increasing numbers of studies have demonstrated the alteration of the gut microbiome in pathological states including hypertension. These observations suggest the involvement of the intestinal microbiome in the development and/or maintenance of hypertension. A reciprocal congenic strain of Milan hypertensive rat (NA rat), harbouring a missense mutation in the gene encoding the alpha subunit of the membrane-skeletal protein adducin (Add1), develops hypertension starting from 3 months after birth. Preliminary studies on NA rats and its littermate Milan normotensive (MN) rats showed diverse expression patterns of renal sodium transporters/ion channels in two strains of rats, indicating a putative role of altered renal salt handling on the enhanced blood pressure in NA rats (unpublished data). Based on this background, the aim of this study was to investigate a possible connection between the gut microbiome and blood pressure phenotypes in these two strains. Furthermore, we evaluated whether the exchange of faeces between the two strains could transfer the phenotypes through the gut microbiome. Finally, mechanisms underlying the altered phenotype after microbiome exchange were investigated. Method Hypertensive NA rats and normotensive MN rats were subjected to ‘homogenization (HOM)’ of the microbiome after birth, which consisted of the exchange of bedding containing faeces from either strain, followed by co-housing of MN and NA rats in the same cage (MN-HOM and NA-HOM groups). For the baseline (BSL) condition, rats were homogenized within the same strain (MN-BSL and NA-BSL). At the age of 5 months, blood pressure measurement was performed using a non-invasive tail-cuff BP-2000 Blood Pressure Analysis system. Faeces from each rat were collected for microbiota metataxonomic analysis using next generation sequencing of 16S ribosome encoding DNA. At the end of the treatment, rats were sacrificed for the collections of blood and organs to assess the expressions of genes involved in renal salt reabsorption. Results Systolic blood pressure (SBP) in MN-BSL was averaged at 143.6 mmHg, while NA-BSL showed average SBP 163.3 mmHg, confirming the hypertensive phenotype in NA rats at baseline (P<0.001). Interestingly, MN-HOM showed a significantly enhanced SBP compared to MN-BSL, reaching 153.5 mmHg (P = 0.005). On the other hand, the average SBP of NA-HOM was163.7 mmHg, indicating that homogenization did not significantly impact blood pressure in NA rats. Although the MN-HOM group showed significantly increased SBP compared with MN-BSL group, the average SBP of MN-HOM was still significantly lower than both the NA-BSL and NA-HOM groups. Different gut microbiota compositions were observed in the two strains of rats at baseline, and HOM altered both. Conclusion We have demonstrated that the hypertensive phenotype in NA rats was transferred to normotensive MN rats through the exchange of gut microbiota, indicating that the intestinal microbiota and/or metabolites derived therefrom could eventually modulate blood pressure. Further studies including immunoblotting as well as uremic toxin analyses are required to unveil the molecular mechanisms by which the gut microbiome modulates blood pressure.

Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas.

Colorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rectal cancer (READ). This new perspective could improve diagnosis and treatment of both carcinomas. RNA-binding proteins (RBPs), as critical regulators of every hallmark of cancer, could fulfill the need to identify sensitive biomarkers for COAD and READ separately. To detect new RBPs involved in COAD and READ progression, here we used a multidata integration strategy to prioritize tumorigenic RBPs. We analyzed and integrated 1) RBPs genomic and transcriptomic alterations from 488 COAD and 155 READ patients, 2) ∼ 10,000 raw associations between RBPs and cancer genes, 3) ∼ 15,000 immunostainings, and 4) loss-of-function screens performed in 102 COREAD cell lines. Thus, we unraveled new putative roles of NOP56, RBM12, NAT10, FKBP1A, EMG1, and CSE1L in COAD and READ progression. Interestingly, FKBP1A and EMG1 have never been related with any of these carcinomas but presented tumorigenic features in other cancer types. Subsequent survival analyses highlighted the clinical relevance of FKBP1A, NOP56, and NAT10 mRNA expression to predict poor prognosis in COREAD and COAD patients. Further research should be performed to validate their clinical potential and to elucidate their molecular mechanisms underlying these malignancies.

Conserved organ-specific microbial assemblages in different populations of a terrestrial crab.

Microorganisms are ubiquitous in the environment and provide genetic and physiological functions to multicellular organisms. Knowledge on the associated microbiota is becoming highly relevant to understand the host's ecology and biology. Among invertebrates, many examples of endosymbiosis have been described, such as those in corals, ants, and termites. At present, however, little is known on the presence, diversity, and putative roles of the microbiota associated to brachyuran crabs in relation to their environment. In this work we investigated the associated microbiota of three populations of the terrestrial brachyuran crab Chiromantes haematocheir to find evidence of a conserved organ-specific microbiome unrelated to the population of origin and dissimilar from environmental microbial assemblages. Bacterial 16S rRNA gene and fungal ITS sequences were obtained from selected crab organs and environmental matrices to profile microbial communities. Despite the presence of truly marine larval stages and the absence of a gregarious behaviour, favouring microbiota exchanges, we found common, organ-specific microbiota, associated with the gut and the gills of crabs from the different populations (with more than 15% of the genera detected specifically enriched only in one organ). These findings suggest the presence of possible functional roles of the organ-specific microbiota.

Crosstalk between diacylglycerol kinase and protein kinase A in the regulation of airway smooth muscle cell proliferation

BackgroundDiacylglycerol kinase (DGK) regulates intracellular signaling and functions by converting diacylglycerol (DAG) into phosphatidic acid. We previously demonstrated that DGK inhibition attenuates airway smooth muscle (ASM) cell proliferation, however, the mechanisms mediating this effect are not well established. Given the capacity of protein kinase A (PKA) to effect inhibition of ASM cells growth in response to mitogens, we employed multiple molecular and pharmacological approaches to examine the putative role of PKA in the inhibition of mitogen-induced ASM cell proliferation by the small molecular DGK inhibitor I (DGK I).MethodsWe assayed cell proliferation using CyQUANT™ NF assay, protein expression and phosphorylation using immunoblotting, and prostaglandin E2 (PGE2) secretion by ELISA. ASM cells stably expressing GFP or PKI-GFP (PKA inhibitory peptide-GFP chimera) were stimulated with platelet-derived growth factor (PDGF), or PDGF + DGK I, and cell proliferation was assessed.ResultsDGK inhibition reduced ASM cell proliferation in cells expressing GFP, but not in cells expressing PKI-GFP. DGK inhibition increased cyclooxygenase II (COXII) expression and PGE2 secretion over time to promote PKA activation as demonstrated by increased phosphorylation of (PKA substrates) VASP and CREB. COXII expression and PKA activation were significantly decreased in cells pre-treated with pan-PKC (Bis I), MEK (U0126), or ERK2 (Vx11e) inhibitors suggesting a role for PKC and ERK in the COXII-PGE2-mediated activation of PKA signaling by DGK inhibition.ConclusionsOur study provides insight into the molecular pathway (DAG-PKC/ERK-COXII-PGE2-PKA) regulated by DGK in ASM cells and identifies DGK as a potential therapeutic target for mitigating ASM cell proliferation that contributes to airway remodeling in asthma.

The putative role of the epipeptide EpeX in Bacillus subtilis intra-species competition.

Bacteria engage in competitive interactions with neighbours that can either be of the same or different species. Multiple mechanisms are deployed to ensure the desired outcome and one tactic commonly implemented is the production of specialised metabolites. The Gram-positive bacterium Bacillus subtilis uses specialized metabolites as part of its intra-species competition determinants to differentiate between kin and non-kin isolates. It is, however, unknown if the collection of specialized metabolites defines competitive fitness when the two isolates start as a close, interwoven community that grows into a densely packed colony biofilm. Moreover, the identity of specialized metabolites that have an active role in defining the outcome of an intra-species interaction has not been revealed. Here, we determine the competition outcomes that manifest when 21 environmental isolates of B. subtilis are individually co-incubated with the model isolate NCIB 3610 in a colony biofilm. We correlated these data with the suite of specialized metabolite biosynthesis clusters encoded by each isolate. We found that the epeXEPAB gene cluster was primarily present in isolates with a strong competitive phenotype. This cluster is responsible for producing the epipeptide EpeX. We demonstrated that EpeX is a competition determinant of B. subtilis in an otherwise isogenic context for NCBI 3610. However, when we competed the NCIB 3610 EpeX-deficient strain against our suite of environmental isolates we found that the impact of EpeX in competition is isolate-specific, as only one of the 21 isolates showed increased survival when EpeX was lacking. Taken together, we have shown that EpeX is a competition determinant used by B. subtilis that impacts intra-species interactions but only in an isolate-specific manner.

Weighted gene co-expression network analysis of nitrogen (N)-responsive genes and the putative role of G-quadruplexes in N use efficiency (NUE) in rice.

Rice is an important target to improve crop nitrogen (N) use efficiency (NUE), and the identification and shortlisting of the candidate genes are still in progress. We analyzed data from 16 published N-responsive transcriptomes/microarrays to identify, eight datasets that contained the maximum number of 3020 common genes, referred to as N-responsive genes. These include different classes of transcription factors, transporters, miRNA targets, kinases and events of post-translational modifications. A Weighted gene co-expression network analysis (WGCNA) with all the 3020 N-responsive genes revealed 15 co-expression modules and their annotated biological roles. Protein-protein interaction network analysis of the main module revealed the hub genes and their functional annotation revealed their involvement in the ubiquitin process. Further, the occurrences of G-quadruplex sequences were examined, which are known to play important roles in epigenetic regulation but are hitherto unknown in N-response/NUE. Out of the 3020 N-responsive genes studied, 2298 contained G-quadruplex sequences. We compared these N-responsive genes containing G-quadruplex sequences with the 3601 genes we previously identified as NUE-related (for being both N-responsive and yield-associated). This analysis revealed 389 (17%) NUE-related genes containing G-quadruplex sequences. These genes may be involved in the epigenetic regulation of NUE, while the rest of the 83% (1811) genes may regulate NUE through genetic mechanisms and/or other epigenetic means besides G-quadruplexes. A few potentially important genes/processes identified as associated with NUE were experimentally validated in a pair of rice genotypes contrasting for NUE. The results from the WGCNA and G4 sequence analysis of N-responsive genes helped identify and shortlist six genes as candidates to improve NUE. Further, the hitherto unavailable segregation of genetic and epigenetic gene targets could aid in informed interventions through genetic and epigenetic means of crop improvement.

Seasonal fluctuations and diversity of Ingoldian mycobiota in two water bodies receiving different effluents at Assiut Governorate (Upper Egypt)

In the current study, fifty-eight Ingoldain fungal species assignable to forty-one genera were recovered from two water bodies receiving the treated sewage and the effluents of oils and soaps factory at Assiut Governorate (Upper Egypt), of which Anguillospora, Amniculicola, Flagellospora, and Mycocentrospora were the most prevalent genera. The most widespread identified species were Anguillospora furtive, Amniculicola longissima and Flagellospora fusarioides. Forty-three species were identified for the first time in Egypt. The most Ingoldain taxa were estimated for El-Zinnar canal, with the highest recorded taxa in winter. Whereas, the highest dominance of Ingoldian fungi was estimated for the El-Ibrahimia canal. The highest Simpson and Shannon diversity indexes were estimated for El-Zinnar canal samples recording 0.9683 and 3.741, respectively. The poorest water sites with Ingoldian fungi were those exposed directly to either treated sewage or industrial effluents, with which relatively higher values of water conductivity, cations and anions. Water temperature was the main abiotic factor driving the seasonal occurrence of Ingoldian fungi. It is interesting to isolate some Ingoldian fungal species from the stressful water sites receiving the effluents which provide valuable insights regarding their adaptation, predictive and putative role as bioindicators and their potentiality in pollutants degradation, organic decomposition, and transformation of xenobiotic compounds.

The microglial innate immune receptors TREM-1 and TREM-2 in the anterior cingulate cortex (ACC) drive visceral hypersensitivity and depressive-like behaviors following DSS-induced colitis

Inflammatory bowel disease (IBD) is a chronic condition with a high recurrence rate. To date, the clinical treatment of IBD mainly focuses on inflammation and gastrointestinal symptoms while ignoring the accompanying visceral pain, anxiety, depression, and other emotional symptoms. Evidence is accumulating that bi-directional communication between the gut and the brain is indispensable in the pathophysiology of IBD and its comorbidities. Increasing efforts have been focused on elucidating the central immune mechanisms in visceral hypersensitivity and depression following colitis. The triggering receptors expressed on myeloid cells-1/2 (TREM-1/2) are newly identified receptors that can be expressed on microglia. In particular, TREM-1 acts as an immune and inflammatory response amplifier, while TREM-2 may function as a molecule with a putative antagonist role to TREM-1. In the present study, using the dextran sulfate sodium (DSS)-induced colitis model, we found that peripheral inflammation induced microglial and glutamatergic neuronal activation in the anterior cingulate cortex (ACC). Microglial ablation mitigated visceral hypersensitivity in the inflammation phase rather than in the remission phase, subsequently preventing the emergence of depressive-like behaviors in the remission phase. Moreover, a further mechanistic study revealed that overexpression of TREM-1 and TREM-2 remarkably aggravated DSS-induced neuropathology. The improved outcome was achieved by modifying the balance of TREM-1 and TREM-2 via genetic and pharmacological means. Specifically, a deficiency of TREM-1 attenuated visceral hyperpathia in the inflammatory phase, and a TREM-2 deficiency improved depression-like symptoms in the remission phase. Taken together, our findings provide insights into mechanism-based therapy for inflammatory disorders and establish that microglial innate immune receptors TREM-1 and TREM-2 may represent a therapeutic target for the treatment of pain and psychological comorbidities associated with chronic inflammatory diseases by modulating neuroinflammatory responses.

Downregulation of Yap1 during limb regeneration results in defective bone formation in axolotl

The Hippo pathway plays an imperative role in cellular processes such as differentiation, regeneration, cell migration, organ growth, apoptosis, and cell cycle. Transcription coregulator component of Hippo pathway, YAP1, promotes transcription of genes involved in cell proliferation, migration, differentiation, and suppressing apoptosis. However, its role in epimorphic regeneration has not been fully explored. The axolotl is a well-established model organism for developmental biology and regeneration studies. By exploiting its remarkable regenerative capacity, we investigated the role of Yap1 in the early blastema stage of limb regeneration. Depleting Yap1 using gene-specific morpholinos attenuated the competence of axolotl limb regeneration evident in bone formation defects. To explore the affected downstream pathways from Yap1 down-regulation, the gene expression profile was examined by employing LC-MS/MS technology. Based on the generated data, we provided a new layer of evidence on the putative roles of increased protease inhibition and immune system activities and altered ECM composition in diminished bone formation capacity during axolotl limb regeneration upon Yap1 deficiency. We believe that new insights into the roles of the Hippo pathway in complex structure regeneration were granted in this study.

Insights into uterine fluid proteins and putative roles on maternal recognition of pregnancy

The embryo is dependent on uterine secretions in early pregnancy and notably around the time of maternal recognition of pregnancy (MRP). This study aimed to identify key proteins in the uterine fluid and embryo before and around the time of MRP. We hypothesized that uterine fluid has a unique signature of proteins around the time of MRP. Mares were bred to a fertile stallion until ten embryos were obtained for each of days 7, 10 and12 post-ovulation. A gynecological tampon was inserted in utero for collection of the uterine fluid. Embryo flushing was carried out with Lactated Ringers Solution. Recovered embryos were flushed in DPBS, and then stored in DPBS enriched with proteinase inhibitors at -80°C. Uterine fluid was centrifuged, and the supernatant was stored at -80°C until analysis. The embryo was sonicated, centrifuged as the uterine fluid, and then stored at -80°C until analysis. Total protein was determined by the acid bicinchoninic method, in-gel tryptic digestion was carried out and samples were analyzed by mass-spectrometry (ESI-Q-TOF-MS/MS). Gene-ontology was carried out on a Panther, vs17.0. Multivariate-analyses based on principle component analysis (PCA), and partial least squares discriminant analysis-variables importance (PLS-DA/VIP) score were performed with Metaboanalyst, v5.0 via R-studio. The total protein numbers found at Days 7, 10, and 12 were 75, 81 and 84 in the uterine fluid and 151, 139, and 178 inthe embryos, respectively. The most abundant proteins (VIP-score, α>1.5) present in the embryos at Days 7, 10, and 12 were 0, 6 and 2; whereas uterine fluid had 0, 3 and 2 for the same respective days. Molecular functions found on gene-ontology were catalytic activity and binding in both samples from embryos and uterine fluids. There was a remarkable change in PCA from Day 7 to Day 10/12 in the embryo and uterine fluid proteins. Proteins found in great abundance in the embryos PLS-DA/VIP-score analysis were related to protection against thermal-stress, protein folding, stabilization, translation, lipid-metabolism and cell-structure. Cathepsin-B is involved with endometrial remodeling and implantation, but its role in the horse remains to be determined. Uterine fluid had proteins associated with the transport of molecules with low-molecular-weight; in the upregulation of the ERK1- and ERK2-cascades, which are essential for cell-proliferation, differentiation, adhesion, migration, survival; and calcium/phosphorus metabolism. Herein is the first description of Stanniocalcin-1 in equine embryos. In conclusion, the proteins found in utero may play a role in the MRP and the embryo proteins were related to mobility and protection functions. Acknowledgements: The Mass Spectrometry Facility at Brazilian Biosciences National Laboratory (LNBio), CNPEM, Campinas, Brazil is thanked for their support with the use of equipment.

Female intrasexual competitiveness interacts with body mass index to predict willingness to use a risky diet pill.

Previous research has highlighted the putative role of intrasexual competition (IC) in predicting women's body dissatisfaction, weight loss effort, and, at its extreme, eating disorders. However, extant research reporting on these links is limited by its exclusion of potential confounds, including psychopathologies such as depression. Moreover, it is presently unclear whether women higher in body mass index (BMI) may be more prone to the influence of IC in taking dieting risks. To address these gaps in the literature, 189 young adult women completed measures of IC, depressive symptoms, willingness to use a risky diet pill, and had their height and weight measured. Results showed that IC interacted with BMI to predict willingness to use a risky diet pill, such that women high in both IC and BMI were most likely to take the risky diet pill. Further exploratory analyses considering potential directional links between BMI and depression supported mediating roles of depression (from BMI) and BMI (from depression) in predicting willingness to use a risky diet pill. Results suggest that links between IC and dieting risks may be moderated by women's BMI, and that these links hold when considering depressive symptoms. Future longitudinal research would benefit from a better understanding of the potential directional links between BMI, depression, and diet pill use.

A Putative Role of Candida albicans in Promoting Cancer Development: A Current State of Evidence and Proposed Mechanisms.

Candida albicans is a commensal fungal species that commonly colonizes the human body, but it is also a pervasive opportunistic pathogen in patients with malignant diseases. A growing body of evidence suggests that this fungus is not only coincidental in oncology patients, but may also play an active role in the development of cancer. More specifically, several studies have investigated the potential association between C. albicans and various types of cancer, including oral, esophageal, and colorectal cancer, with a possible role of this species in skin cancer as well. The proposed mechanisms include the production of carcinogenic metabolites, modulation of the immune response, changes in cell morphology, microbiome alterations, biofilm production, the activation of oncogenic signaling pathways, and the induction of chronic inflammation. These mechanisms may act together or independently to promote cancer development. Although more research is needed to fully grasp the potential role of C. albicans in carcinogenesis, the available evidence suggests that this species may be an active contributor and underscores the importance of considering the impact of the human microbiome on cancer pathogenesis. In this narrative review, we aimed to summarize the current state of evidence and offer some insights into proposed mechanisms.

Phytochemical Characterisation, Antioxidant and Antidiabetic activity of extracts of Neptunia prostrata Linn.

The herb Neptunia prostrata Linn. Is belonging to the family Mimosaceae have been used in folkloric medicine in the North-eastern states of Indiaof Assam and Tripura by indigenous herbal healers since time immemorial but there is a scarcity of any background study documenting its use as an antimicrobial herb. For the same, plants were collected and authenticated. Following identification of these herbs methanolic, ethanolic, pet ether and chloroform extracts were prepared using soxhletion. Acute toxicity study as per OECD guidelines 420 was assessed in wistar albino rats and in swiss albino mice (n=5) of both sexes at doses of 2000mg/kg body weight and did not reveal any morbidity or mortality in the animals within the stipulated period.Phytochemical screening was performed on all four extracts of Neptunia prostrata. Phytochemical constituents depicted presence of glycoside, flavonoids in only ethanolic, methanolic and chloroform extracts. Alkaloids were present in the chloroform extract. The antimicrobial activity was performed by disc agar diffusion method with respect to amoxicillin at standard doses against ATCC strains of Gram positive Staphylococcus aureus, Bacillus subtilis and Gram negative Salmonella typhi. The herbs showed antioxidant activity comparable to standard antioxidants in-vitro such as Ascorbic acid (Vitamin C) with comparable IC 50 values. Results of the antibacterial assay on the basis of zone of inhibition (mm) and MIC values of extracts of the extract (NPHE) under study to suggest these two indigenous herb have conspicuous and potent putative role in the therapeutics of a vast plethora bacterial infections that need to be corroborated for the expansion of future prospective in-vivo studies with larger sample size.

Evidence That PbrSAUR72 Contributes to Iron Deficiency Tolerance in Pears by Facilitating Iron Absorption.

Iron is an essential trace element for plants; however, low bioactive Fe in soil continuously places plants in an Fe-deficient environment, triggering oxidative damage. To cope with this, plants make a series of alterations to increase Fe acquisition; however, this regulatory network needs further investigation. In this study, we found notably decreased indoleacetic acid (IAA) content in chlorotic pear (Pyrus bretschneideri Rehd.) leaves caused by Fe deficiency. Furthermore, IAA treatment slightly induced regreening by increasing chlorophyll synthesis and Fe2+ accumulation. At that point, we identified PbrSAUR72 as a key negative effector output of auxin signaling and established its close relationship to Fe deficiency. Furthermore, the transient PbrSAUR72 overexpression could form regreening spots with increased IAA and Fe2+ content in chlorotic pear leaves, whereas its transient silencing does the opposite in normal pear leaves. In addition, cytoplasm-localized PbrSAUR72 exhibits root expression preferences and displays high homology to AtSAUR40/72. This promotes salt tolerance in plants, indicating a putative role for PbrSAUR72 in abiotic stress responses. Indeed, transgenic plants of Solanum lycopersicum and Arabidopsis thaliana overexpressing PbrSAUR72 displayed less sensitivity to Fe deficiency, accompanied by substantially elevated expression of Fe-induced genes, such as FER/FIT, HA, and bHLH39/100. These result in higher ferric chelate reductase and root pH acidification activities, thereby hastening Fe absorption in transgenic plants under an Fe-deficient condition. Moreover, the ectopic overexpression of PbrSAUR72 inhibited reactive oxygen species production in response to Fe deficiency. These findings contribute to a new understanding of PbrSAURs and its involvement in Fe deficiency, providing new insights for the further study of the regulatory mechanisms underlying the Fe deficiency response.

0625 Sleep when the baby sleeps? The effect of daytime nap behaviors on postpartum depression severity: a stress buffering hypothesis

Abstract Introduction The early postpartum is a time of expected maternal sleep loss, normalized as part of infant care. While short duration and disrupted nocturnal sleep are posited risk factors for postpartum depression (PPD), the role of daytime sleep remains less understood, despite the widespread recommendation that mothers sleep when their baby is sleeping. This study examined associations between napping, stress, and longitudinal PPD in a sample of in a sample of healthy first-time mothers, using a prospective ambulatory field study design. Methods Fifty primiparous women (62% non-White; mean age=32 years) without a history of sleep disorders or psychopathology completed 10-days (9-nights) of actigraphy and sleep diaries at postpartum week 6. Sleep variables included nighttime duration and efficiency, and daytime nap frequency, timing and duration. Participants completed 3-days of superimposed ecological momentary assessment (EMA) rating naturalistic infant-related stressors (task demand; effort-reward-imbalance) at four daily intervals. Hierarchical mixed models tested whether daytime sleep characteristics predicted lower depression levels (via Edinburgh Postnatal-Depression Scale - EPDS) at 6-weeks, 8-weeks, and 3-months postpartum. Time-varying within-person covariates included time-of-day, baseline depression and anxiety (via Generalized-Anxiety-Disorder-7 scores), and previous night sleep. To test the putative stress-protective role of napping, we examined pre-post nap differences in EMA ratings. Results Sixty percent (n = 30/47) of women napped regularly (>3x/1 week, between 1-5 PM, < 90 min by both diary and actigraphy), rating 80% of these naps “intentional.” Women with greater nap regularity at 6-weeks had lower depression levels at all timepoints (Betas = -2.4(1.6); -1.4(.5), -.5(.01) ps<.001, respectively), and less of an increase in depression symptoms at 3-months postpartum, compared to non-nappers [Beta(SE)=-1.2 (.5); R^2=.21; p<.001]. At 6-weeks, regular nappers reported lower stress post-nap (effort-reward-imbalance; demand) [Beta(SE)=-6.3(1.4); 1.2(.12,), R^2=.27, .32, respectively; ps<.01]. Conclusion This study demonstrates a contemporaneous mood-protective role of daytime sleep in a perinatal sample, using 24-hr objective sleep assessment coupled with daily assessments of naturalistic stressors. Moreover, these results provide support for the protective role of regular daytime sleep on development of PPD over time. Among new mothers who regularly nap, lowered post-nap stress may be one pathway through which daytime sleep buffers against PPD severity. Support (if any) NIMH-1R36MH118000-01, CTSI89431, T32-HL007713

Beyond the Microbiota: Understanding the Role of the Enteric Nervous System in Parkinson's Disease from Mice to Human.

The enteric nervous system (ENS) is a nerve network composed of neurons and glial cells that regulates the motor and secretory functions of the gastrointestinal (GI) tract. There is abundant evidence of mutual communication between the brain and the GI tract. Dysfunction of these connections appears to be involved in the pathophysiology of Parkinson's disease (PD). Alterations in the ENS have been shown to occur very early in PD, even before central nervous system (CNS) involvement. Post-mortem studies of PD patients have shown aggregation of α-synuclein (αS) in specific subtypes of neurons in the ENS. Subsequently, αS spreads retrogradely in the CNS through preganglionic vagal fibers to this nerve's dorsal motor nucleus (DMV) and other central nervous structures. Here, we highlight the role of the ENS in PD pathogenesis based on evidence observed in animal models and using a translational perspective. While acknowledging the putative role of the microbiome in the gut-brain axis (GBA), this review provides a comprehensive view of the ENS not only as a "second brain", but also as a window into the "first brain", a potentially crucial element in the search for new therapeutic approaches that can delay and even cure the disease.

The Oncogenic Role of Cyclin-Dependent Kinase Inhibitor 2C in Lower-Grade Glioma.

Lower-grade gliomas (LGGs) are slow-growing, indolent tumors that usually affect younger patients and present a therapeutic challenge due to the heterogeneity of their clinical presentation. Dysregulation of cell cycle regulatory factors is implicated in the progression of many tumors, and drugs that target cell cycle machinery have shown efficacy as promising therapeutic approaches. To date, however, no comprehensive study has examined how cell cycle-related genes affect LGG outcomes. The cancer genome atlas (TCGA) data were used as the training set for differential analysis of gene expression and patient outcomes; the Chinese glioma genome atlas (CGGA) was used for validation. Levels of one candidate protein, cyclin-dependent kinase inhibitor 2C (CDKN2C), and its relationship to clinical prognosis were determined using a tissue microarray containing 34 LGG tumors. A nomogram was constructed to model the putative role of candidate factors in LGG. Cell type proportion analysis was performed to evaluate immune cell infiltration in LGG. Various genes encoding cell cycle regulatory factors showed increased expression in LGG and were significantly related to isocitrate dehydrogenase and chromosome arms 1p and 19q mutation status. CDKN2C expression independently predicted the outcome of LGG patients. High M2 macrophage values along with elevated CDKN2C expression were associated with poorer prognosis in LGG patients. CDKN2C plays an oncogenic role in LGG, which is associated with M2 macrophages.

Royal jelly mediates fibrotic signaling, collagen cross-linking and cell proliferation in cardiac fibroblasts

Royal jelly (RJ) is a multifunctional bee product with a unique composition and wide-ranging biological properties, including antioxidant, anti-inflammatory and antiproliferative activities. Still, little is known about the possible myocardial protective properties of RJ. Considering that sonication could enhance RJ bioactivity, this study aimed to assess the effects of non-sonicated (NS) and sonicated (S) RJ on fibrotic signaling, cell proliferation, and collagen production in cardiac fibroblasts. S-RJ was produced by ultrasonication at 20 kHz. Ventricular fibroblasts isolated from neonatal rats were cultured and treated with different concentrations of NS-RJ or S-RJ (0, 50, 100, 150, 200, and 250 µg/well). S-RJ significantly depressed the expression levels of transglutaminase 2 (TG2) mRNA across all the concentrations tested and was inversely associated with the expression of this profibrotic marker. S-RJ and NS-RJ displayed distinct dose-dependent effects on mRNA expression of several other profibrotic, proliferation, and apoptotic markers. Unlike NS-RJ, S-RJ elicited strong negative dose-dependent relationships with the expression of profibrotic markers (TG2, COL1A1, COL3A1, FN1, CTGF, MMP-2, α-SMA, TGF-β1, CX43, periostin), as well as proliferation (CCND1) and apoptotic (BAX, BAX/BCL-2) markers, indicating that RJ dose-response effects were significantly modified by sonification. NS-RJ and S-RJ increased the content of soluble collagen, while decreasing collagen cross-linking. Collectively, these findings show that S-RJ has a greater range of action than NS-RJ for downregulating the expression of biomarkers associated with cardiac fibrosis. Reduced biomarker expression and collagen cross-linkages upon cardiac fibroblast treatment with specific concentrations of S-RJ or NS-RJ suggests putative roles and mechanisms by which RJ may confer some protection against cardiac fibrosis.

Functional characterization of the gonococcal polyphosphate pseudo-capsule.

Neisseria gonorrhoeae is an exclusively human pathogen able to evade the host immune system through multiple mechanisms. Gonococci accumulate a large portion of phosphate moieties as polyphosphate (polyP) on the exterior of the cell. Although its polyanionic nature has suggested that it may form a protective shield on the cell surface, its role remains controversial. Taking advantage of a recombinant His-tagged polyP-binding protein, the presence of a polyP pseudo-capsule in gonococcus was demonstrated. Interestingly, the polyP pseudo-capsule was found to be present in specific strains only. To investigate its putative role in host immune evasion mechanisms, such as resistance to serum bactericidal activity, antimicrobial peptides and phagocytosis, the enzymes involved in polyP metabolism were genetically deleted, generating mutants with altered polyP external content. The mutants with lower polyP content on their surface compared to the wild-type strains, became sensitive to complement-mediated killing in presence of normal human serum. Conversely, naturally serum sensitive strains that did not display a significant polyP pseudo-capsule became resistant to complement in the presence of exogenous polyP. The presence of polyP pseudo-capsule was also critical in the protection from antibacterial activity of cationic antimicrobial peptide, such as cathelicidin LL-37. Results showed that the minimum bactericidal concentration was lower in strains lacking polyP than in those harboring the pseudo-capsule. Data referring to phagocytic killing resistance, assessed by using neutrophil-like cells, showed a significant decrease in viability of mutants lacking polyP on their cell surface in comparison to the wild-type strain. The addition of exogenous polyP overturned the killing phenotype of sensitive strains suggesting that gonococcus could exploit environmental polyP to survive to complement-mediated, cathelicidin and intracellular killing. Taken together, data presented here indicate an essential role of the polyP pseudo-capsule in the gonococcal pathogenesis, opening new perspective on gonococcal biology and more effective treatments.