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1.
Langmuir ; 40(18): 9509-9519, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38648179

ABSTRACT

Water can be sustainably and ecologically converted by electrocatalysts into hydrogen and oxygen, which, in turn, can be converted into energy. However, the advancement of using water as green energy is hampered by limitations in the study of high-performance catalysts. The purpose of this study was to construct an electrocatalyst by anchoring well-dispersed multiwalled carbon nanotubes (MWCNTs) on nickel-copper (NiCu-MOF) nanoblocks through a simple solvothermal method. The synthesis of NiCu-MOF@MWCNTs demonstrated exceptional electrocatalytic performance for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in an alkaline medium. At 10 mA cm-2 in 1.0 M KOH, the OER and HER performance of the catalyst displays a relatively low overpotential, with only 220 and 78 mV, respectively. Furthermore, the catalytic activity remained unchanged for 24 h in 1.0 M KOH. This performance was superior to the majority of electrocatalysts that have been reported. This was achieved by utilizing the strong synergy that exists between MWCNTs and bimetallic (Ni-Cu) nano blocks present in the metal-organic framework. The enhanced electrocatalytic activity of the nanocomposite can be attributed to the synergistic impact caused by its various components.

2.
J Fluoresc ; 31(2): 427-436, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33411228

ABSTRACT

Recently, natural products are the powerful carbon source to synthesize carbon dots (CDs) with interesting physical and chemical properties. In this present work, we report a facile hydrothermal synthesis method for preparing fluorescent carbon dots using a biogenic precursor of rice bran without any surface passivation agent. The synthetic methodology was easy, simple, environmental friendly and convenient. Structural and optical properties of the RB-CDs have been studied by UV-visible, Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), Fluorescence spectra and X-ray photoelectron spectroscopy (XPS) techniques. The prepared RB-CDs exhibited green emission upon irradiation with UV light and the calculated fluorescence quantum yield (QY) was found to be 7.4%. The morphological features of the synthesized RB-CDs were characterized by High-Resolution Transmission Electron Microscopy (HR-TEM), the average size of the RB-CDs was found to be 2.96 nm. The synthesized RB-CDs were beneficially applied as a catalyst for the catalytic degradation of methylene blue (MB) dye using NaBH4 as the reducing agent in the ambient conditions. The degradation of MB dye under light illumination was 89.20% in 30 min. Further, the obtained highly fluorescent RB-CDs were efficiently utilized as a fluorescent ink for luminescent pattern printing (patterning agent) in the anti-counterfeiting applications.


Subject(s)
Carbon/chemistry , Fluorescence , Fluorescent Dyes/chemical synthesis , Green Chemistry Technology , Ink , Methylene Blue/chemistry , Oryza/chemistry , Quantum Dots/chemistry , Fluorescent Dyes/chemistry , Particle Size , Spectrometry, Fluorescence
3.
BMC Pregnancy Childbirth ; 16: 23, 2016 Jan 28.
Article in English | MEDLINE | ID: mdl-26821645

ABSTRACT

BACKGROUND: Postpartum hemorrhage remains the leading cause of maternal mortality worldwide. Administration of uterotonics during the third stage of labor is a simple and well established intervention that can significantly decrease the development of postpartum hemorrhage. Little is known about the use of prophylactic uterotonics in peripheral health centers, where the majority of normal deliveries occur. The purpose of this study is to assess health provider current practices and determinants to the use of prophylactic uterotonics in Sierra Leone, a country with one of the highest maternal mortality ratios worldwide. METHODS: This is a mixed methods study using descriptive cross-sectional survey and qualitative interviews in community health facilities in Freetown, Sierra Leone following a comprehensive training on postpartum hemorrhage. Facilities and providers were surveyed between May and June 2014. Qualitative methods were used to identify barriers and facilitators to the use of prophylactic uterotonics. RESULTS: A total of 134 providers were surveyed at 39 periphreal health facilities. Thirteen facilities (39 %) reported an inconsistent supply of oxytocin. The majority of facilities (64 %) stored oxytocin at room temperature. Provider level, in-service training, and leadership role were significantly associated with prophylactic uterotonic use. Overall, 62 % of providers reported routine use. Midwives were most likely to routinely administer uterotonics (93 %), followed by community health officers/assistants (78 %), maternal and child health aides (56 %), and state-enrolled community health nurses (52 %). Of the providers who received in-service training, 67 % reported routine use; of those with no in-service training, 42 % reported routine use. Qualitative analysis revealed that facility protocols, widespread availability, and provider perception of utility facilitated routine use. Common barriers reported included inconsistent supply of uterotonics, lack of knowledge regarding timely administration, and provider attitude regarding utility of uterotonics following normal deliveries. CONCLUSION: There is considerable room for improvement in availability and administration of prophylactic uterotonics. Understanding barriers to routine use may aid in developing multifaceted pre-service and in-service training interventions designed to improve routine intrapartum care.


Subject(s)
Health Personnel/statistics & numerical data , Labor Stage, Third , Oxytocics/therapeutic use , Postpartum Hemorrhage/prevention & control , Practice Patterns, Physicians'/statistics & numerical data , Adult , Community Health Centers , Cross-Sectional Studies , Delivery, Obstetric/methods , Female , Health Personnel/psychology , Humans , Male , Maternal Mortality , Middle Aged , Midwifery/methods , Midwifery/statistics & numerical data , Oxytocin/therapeutic use , Pregnancy , Qualitative Research , Sierra Leone
4.
BMC Complement Altern Med ; 15: 73, 2015 Mar 20.
Article in English | MEDLINE | ID: mdl-25885803

ABSTRACT

BACKGROUND: Management of diabetes without any side effects is still a challenge to the medical system. This leads to increasing demand for natural products with antidiabetic activity with fewer side effects. Grewia hirsuta (Tiliaceae) is a traditional herbal medicinal plant and is reported to possess a variety of pharmacological actions. In the present research, a compound (4Z, 12Z)-cyclopentadeca-4, 12-dienone isolated from Grewia hirsuta was taken as ligand for molecular docking studies. Evaluation of hypoglycemic activity through an extensive in silico docking approach with molecular targets such as aldose reductase, glucokinase, pyruvate dehydrogenase kinase isoform 2, peroxisome proliferator-activated receptor-gamma, glycogen synthase kinase-3, 11ß-Hydroxysteroid dehydrogenase, and glutamine: fructose-6-phosphate amidotransferase were performed. METHODS: Isolation of the (4Z, 12Z)-cyclopentadeca-4,12-dienone from the methanol extract of the leaves of Grewia hirsuta was performed by the column chromatography to yield different fractions. These fractions were then subjected to purification and the structure was elucidated and confirmed by spectroscopic methods including UV, FTIR, (1)H, (13)C NMR and the accurate mass determination was carried out using the Q-TOF mass spectrometer. In-vivo experimentation was performed with evaluation of α-glucosidase, α-amylase and MTT assay that had been reported by the author in the earlier paper. Molecular docking study was performed with GLIDE docking software. RESULTS: The docking studies of the ligand (4Z, 12Z)-cyclopentadeca-4, 12-dienone with seven different target proteins showed that this is a good inhibitor, which docks well with various targets related to diabetes mellitus. Hence (4Z, 12Z)-cyclopentadeca-4,12-dienone can be considered for developing into a potent anti-diabetic drug. CONCLUSION: The results of the current study have revealed that the leaves of the selected plant Grewia hirsuta contains a potential inhibitor for diabetes (4Z, 12Z)-cyclopentadeca-4,12-dienone. Thus enabling a possibility of this plant extract as a new alternative to existing diabetic approaches.


Subject(s)
Cyclopentanes/pharmacology , Diabetes Mellitus, Type 2/metabolism , Enzymes/metabolism , Grewia/chemistry , Hypoglycemic Agents/pharmacology , Plant Extracts/pharmacology , Transcription Factors/metabolism , Aldehyde Reductase/metabolism , Cyclopentanes/isolation & purification , Cyclopentanes/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Fructosephosphates/metabolism , Humans , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/therapeutic use , Molecular Docking Simulation , PPAR gamma/metabolism , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Plant Leaves
5.
Anal Methods ; 16(21): 3413-3429, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38766762

ABSTRACT

The research study describes the development of a hybrid nanocomposite called nitro-doped carbon nanodots/polyaniline/molecularly imprinted polymer (N-CNDs/PAni/MIP). This composite is specifically engineered to function as a durable and flexible dual-response sensor to detect and analyze pharmaceutical organic contaminants (POCs). Powder X-Ray diffraction (PXRD), Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) were employed to perform an exhaustive structural and morphological analysis of N-CNDs/PAni/MIP. N-CNDs/PAni/MIP emitted blue luminescence under ultraviolet irradiation and exhibited typical excitation-dependent emission properties. It can act as fluorescent probe for the detection of CIPRO with high selectivity and sensitivity with an IF value of 4.2. Furthermore, N-CNDs/PAni/MIP exhibited high peroxidase-like catalytic behavior. After adding CIPRO to the N-CNDs/PAni/MIP/TMB/H2O2 system, the blue color of the solution faded due to the reduction of blue ox-TMB to colorless TMB. Based on these two phenomena, with CIPRO as the target analyte, the N-CNDs/PAni/MIP dual sensor showed a minimal detection limit of 70 pM for the fluorescent signaling platform and 3.5 nM for the colorimetric probe with a linear range of 0.038-200 nM. The fluorometric and colorimetric assays based on N-CNDs/PAni/MIP for CIPRO detection were then successfully applied to lentic water as well as to tap water samples, demonstrating the sensitivity and dependability of the instrument. Furthermore, the synthesized PVA (N-CNDs/PAni/MIP) films enable the recognition of CIPRO, and these films have the potential to be integrated into portable sensing devices, providing a practical solution for rapid and on-site detection of CIPRO in various samples.


Subject(s)
Aniline Compounds , Ciprofloxacin , Molecularly Imprinted Polymers , Molecularly Imprinted Polymers/chemistry , Aniline Compounds/chemistry , Ciprofloxacin/analysis , Ciprofloxacin/chemistry , Water Pollutants, Chemical/analysis , Limit of Detection , Molecular Imprinting/methods , Nanocomposites/chemistry , Polymers/chemistry
6.
RSC Adv ; 13(34): 23829-23840, 2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37564255

ABSTRACT

Catalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are at the heart of water oxidation reactions. Despite continuous efforts, the development of OER/HER electrocatalysts with high activity at low cost remains a big challenge. Herein, we report a composite material consisting of Li1.05Ni0.5Mn1.5O4, Li1.05Ni0.5 La0.10Mn1.40O4, and Li1.05Ni0.5 Nd0.10Mn1.40O4 as a bifunctional electrocatalyst for OER and HER applications. Though the catalyst has a modest activity for HER, it exhibits high OER activity thereby making it a better nonprecious electrocatalyst for both OER and HER. The catalytic activity arises from the synergetic effects between LNM-La and LNM-Nd by a facile route that shows excellent and durable bifunctional catalytic activity for OER and HER in the alkaline medium developed. The LNM, LNM-La, and, LNM-Nd displayed current densities of 2.17 V, 1.68 V, and 1.93 V vs. RHE at 10 mA cm-2 respectively. The Tafel slope values obtained for LNM, LNM-La, and LNM-Nd are about 419 mV dec-1, 118 mV dec-1, and 378 mV dec-1 respectively. These results indicate the superior electrocatalytic activity of LNM-La with facile OER kinetics.

7.
Environ Sci Pollut Res Int ; 30(39): 90689-90707, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37464206

ABSTRACT

The present study is mainly concerned with the development of cost-efficient composite material utilized to produce one-dimensional manganese oxide (α-MnO2) nanoparticles coated on two-dimensional graphitic carbon nitrides (HT-GCN) as nanocomposite (α-MnO2/HT-GCN) for highly efficient CIP degradation. The α-MnO2 nanoparticles (NPs) were prepared by a simple hydrothermal technique before being decorated on HT-GCN (H denotes protonation and T represents thermal-decomposition-graphitic carbon nitride). Tauc plots were used to calculate the band gap values of the photocatalysts α-MnO2 (1.74 eV), GCN (2.84 eV), HT-GCN (2.63 eV), and α-MnO2/HT-GCN (2.31 eV). The mechanism was investigated by various scavengers, particularly isopropanol (•OH) makes a significant role in the photodegradation process. The degradation percentage for ciprofloxacin was 89.2% and the rate of reaction R2 = 0.9913. This study demonstrates a unique method for developing a heterojunction-based nanocomposite of α-MnO2/HT-GCN, which exhibit better light absorption performance.


Subject(s)
Ciprofloxacin , Nanocomposites , Manganese Compounds , Oxides
8.
ACS Omega ; 7(1): 1368-1379, 2022 Jan 11.
Article in English | MEDLINE | ID: mdl-35036798

ABSTRACT

In this article, we designed a fluorometric sensor based on nitrogen-passivated carbon dots infused with a molecularly imprinted polymer (N-CDs@MIP) via a reverse microemulsion technique using 3-aminopropyltriethoxysilane as a functional monomer, tetraethoxysilane as a cross-linker, and 2,4,6-trinitrophenol (TNP) as a template. The synthesized probe was used for selective and sensitive detection of trace amounts of TNP. The infusion of N-CDs (QY-21.6 percent) with a molecularly imprinted polymer can increase the fluorescent sensor sensitivity to detect TNP. Removal of template molecules leads to the formation of a molecularly imprinted layer, and N-CDs@MIP fluorescence response was quenched by TNP. The developed fluorescence probe shows a fine linear range from 0.5 to 2.5 nM with a detection limit of 0.15 nM. The synthesized fluorescent probe was used to analyze TNP in regular tap and lake water samples.

9.
ACS Omega ; 7(15): 12825-12834, 2022 Apr 19.
Article in English | MEDLINE | ID: mdl-35474775

ABSTRACT

The demand for modern organic pollutant treatment has prompted the development of environmentally acceptable photocatalytic processes. In this work, we report novel nitrogen and sulfur codoped graphene quantum dot (S,N-GQD) based photocatalysts and fluorescent ink for the first time. For the degradation of organic dyes under visible irradiation, a hydrothermal technique was employed to generate S,N-GQD green nanomaterials. The synthesized samples were examined using XRD, HR-TEM, EDX, FT-IR, PL, and UV-vis spectroscopy. UV-DRS was used to determine the energy band gap of S,N-GQDs, and it was obtained to be around ∼2.54 eV. To explore the catalytic behavior of the produced S,N-GQDs as green nanomaterials, organic dyes (i.e., crystal violet and Alizarin yellow) have been used as a reference dye in this study. Using several radical scavenging agents, the photocatalytic mechanism was examined. This novel photocatalyst offers a promising alternative for the breakdown of organic pollutants. Moreover, these S,N-GQDs can also be used as fluorescent ink for imaging purposes and security reasons.

10.
Surgery ; 166(6): 1188-1195, 2019 12.
Article in English | MEDLINE | ID: mdl-31466858

ABSTRACT

BACKGROUND: Ensuring timely and high-quality surgery must be a key element of breast cancer control efforts in sub-Saharan Africa. We investigated delays in preoperative care and the impact of on-site versus off-site operation on time to operative treatment of patients with breast cancer at Butaro Cancer Center of Excellence in Rwanda. METHODS: We used a standardized data abstraction form to collect demographic data, clinical characteristics, treatments received, and disease status as of November 2017 for all patients diagnosed with breast cancer at Butaro Cancer Center of Excellence in 2014 to 2015. RESULTS: From 2014 to 2015, 89 patients were diagnosed with stage I to III breast cancer and treated with curative intent. Of those, 68 (76%) underwent curative breast operations, 12 (14%) were lost to follow-up, 7 (8%) progressed, and 2 declined the recommended operation. Only 32% of patients who underwent operative treatment had the operation within 60 days from diagnosis or last neoadjuvant chemotherapy. Median time to operation was 122 days from biopsy if no neoadjuvant treatments were given and 51 days from last cycle of neoadjuvant chemotherapy. Patients who received no neoadjuvant chemotherapy experienced greater median times to operation at Butaro Cancer Center of Excellence (180 days) than at a referral hospital in Kigali (93 days, P = .04). Most patients (60%) experienced a disruption in preoperative care, frequently at the point of surgical referral. Documented reasons for disruptions and delays included patient factors, clinically indicated treatment modifications, and system factors. CONCLUSION: We observed frequent delays to operative treatment, disruptions in preoperative care, and loss to follow-up, particularly at the point of surgical referral. There are opportunities to improve breast cancer survival in Rwanda and other low- and middle-income countries through interventions that facilitate more timely surgical care.


Subject(s)
Breast Neoplasms/surgery , Preoperative Care/standards , Time-to-Treatment , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Continuity of Patient Care , Delivery of Health Care/standards , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Referral and Consultation/standards , Retrospective Studies , Rwanda
11.
BMJ Open ; 6(1): e010083, 2016 Jan 08.
Article in English | MEDLINE | ID: mdl-26747039

ABSTRACT

OBJECTIVES: To assess the impact of a every second matters for mothers and babies uterine balloon tamponade package (ESM-UBT) on provider decisions regarding emergency hysterectomy in cases of uncontrolled postpartum haemorrhage (PPH). DESIGN: Qualitative assessment and analysis of a subgroup extracted from a larger database that contains all UBT device uses among ESM-UBT trained health providers. SETTING: Health facilities in Kenya and Senegal with ESM-UBT training and capable of performing emergency hysterectomies. PARTICIPANTS: All medical doctors who had placed a UBT for uncontrolled PPH subsequent to implementation of ESM-UBT at their facility, and who also had the capabilities of performing emergency hysterectomies. PRIMARY OUTCOME MEASURES: The impact of ESM-UBT on decisions regarding emergency hysterectomy in cases of uncontrolled PPH. RESULTS: 30 of the 31 medical doctors (97%) who fulfilled the inclusion criteria were independently interviewed. Collectively the interviewed medical doctors had placed over 80 UBT devices for uncontrolled PPH since ESM-UBT implementation. All 30 responded that UBT devices immediately controlled haemorrhage and prevented women from being taken to emergency hysterectomy. All 30 would continue to use UBT devices in future cases of uncontrolled PPH. CONCLUSIONS: These preliminary data suggest that following ESM-UBT implementation, emergency hysterectomy for uncontrolled PPH may be averted by use of uterine balloon tamponade.


Subject(s)
Hysterectomy/methods , Postpartum Hemorrhage/prevention & control , Uterine Balloon Tamponade , Clinical Decision-Making , Emergency Treatment/methods , Female , Health Knowledge, Attitudes, Practice , Humans , Kenya , Obstetrics/education , Senegal
12.
Int J Gynaecol Obstet ; 134(1): 83-6, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27085981

ABSTRACT

OBJECTIVE: To understand healthcare providers' experience of incorporating uterine balloon tamponade (UBT) into the national postpartum hemorrhage (PPH) clinical pathway after UBT training. METHODS: In a qualitative study, semi-structured interviews were undertaken with healthcare providers from 50 centers in Freetown, Sierra Leone, between May and June 2014. All eligible healthcare providers (undergone UBT training, actively conducted deliveries, and treated cases of PPH since UBT training) on duty at the time of center visit were interviewed. RESULTS: Sixty-one providers at 47 facilities were interviewed. Bleeding was controlled in 28 (93%) of 30 cases of UBT device placement. Participants reported that UBT devices were easy to insert with only minor challenges, and enabled providers to manage most cases of uncontrolled PPH at their own facility and to refer others in a stable condition. Reported barriers to optimal UBT use included insufficient training and practical experience, and a scarcity of preassembled UBT devices. Facilitators of UBT use included widespread acceptance of UBT, comprehensive and enthusiastic training, and ready availability of UBT devices. CONCLUSION: UBT-used either as a primary endpoint or en route to obtaining advanced care-has been well accepted and integrated into the national PPH pathway by providers in health facilities in Freetown.


Subject(s)
Critical Pathways , Disease Management , Health Personnel/education , Postpartum Hemorrhage/therapy , Uterine Balloon Tamponade/statistics & numerical data , Adolescent , Adult , Female , Humans , Interviews as Topic , Maternal Mortality , Pregnancy , Qualitative Research , Sierra Leone , Young Adult
13.
Int J Gynaecol Obstet ; 135(2): 210-213, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27530220

ABSTRACT

OBJECTIVE: To understand healthcare providers' experiences with improvised uterine balloon tamponade (UBT) for the management of uncontrolled postpartum hemorrhage (PPH). METHODS: In a qualitative descriptive study, in-depth semi-structured interviews were conducted between November 2014 and June 2015 among Kenyan healthcare providers who had previous experience with improvising a UBT device. Interviews were conducted, audio-recorded, and transcribed. RESULTS: Overall, 29 healthcare providers (14 nurse-midwifes, 7 medical officers, 7 obstetricians, and 1 clinical officer) were interviewed. Providers perceived improvised UBT as valuable for managing uncontrolled PPH. Reported benefits included effectiveness in arresting hemorrhage and averting hysterectomy, and ease of use by providers of all levels of training. Providers used various materials to construct an improvised UBT. Challenges to improvising UBT-e.g. searching for materials during an emergency, procuring male condoms, and inserting fluid via a small syringe-were reported to lead to delays in care. Providers described their introduction to improvised UBT through both formal and informal sources. There was universal enthusiasm for widespread standardized training. CONCLUSION: Improvised UBT seems to be a valuable second-line treatment for uncontrolled PPH that can be used by providers of all levels. UBT might be optimized by integrating a standard package across the health system.


Subject(s)
Condoms/statistics & numerical data , Hysterectomy/adverse effects , Postoperative Complications/therapy , Postpartum Hemorrhage/therapy , Uterine Balloon Tamponade/instrumentation , Disease Management , Female , Health Personnel , Humans , Kenya , Maternal Mortality , Qualitative Research
14.
Int J Gynaecol Obstet ; 131(2): 201-4, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26277599

ABSTRACT

OBJECTIVE: To understand provider perceptions and experiences following training in the use of a condom-catheter uterine balloon tamponade (UBT) as second-line treatment for uncontrolled postpartum hemorrhage (PPH) in health facilities in Kenya. METHODS: As part of a qualitative study, interviews of facility-based providers who had managed PPH following comprehensive PPH training were conducted between February and April 2014. Facilities were purposively sampled to represent a range of experience with UBT, facility size, and geography. Interviews continued until thematic saturation was achieved. Interview transcripts were analyzed for themes. RESULTS: Overall, 68 providers from 29 facilities were interviewed, of whom 31 reported experience with UBT placement (25 midwives, 2 clinical officers, 4 medical officers). Qualitative analysis revealed several major themes. Providers used UBT appropriately within the PPH algorithm, although the timing and clinical severity of patients varied. UBT was most commonly used when bleeding was unresponsive to uterotonics, hysterectomy was unavailable, and referral times long. Providers reported that bleeding was arrested following UBT use in all except one patient, who had a suspected coagulopathy. Most providers described UBT as technically easy to use, although three described initial balloon displacement. CONCLUSION: UBT has been readily accepted by providers at all levels of training and is being incorporated into the existing PPH management algorithm in Kenya.


Subject(s)
Attitude of Health Personnel , Delivery, Obstetric/education , Health Personnel/psychology , Postpartum Hemorrhage/therapy , Uterine Balloon Tamponade/psychology , Adult , Female , Health Facilities , Health Personnel/education , Humans , Kenya , Middle Aged , Pregnancy , Qualitative Research , Treatment Outcome , Uterine Balloon Tamponade/instrumentation
15.
J Exp Med ; 211(1): 57-69, 2014 Jan 13.
Article in English | MEDLINE | ID: mdl-24344237

ABSTRACT

Balanced transmembrane signals maintain a competent peripheral B cell pool limited in self-reactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22(-/-[B6])) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag-specific B cells in Ig(Tg) hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.


Subject(s)
B-Lymphocytes/immunology , Cell Death/immunology , Cell Survival/immunology , Endonucleases/metabolism , Self Tolerance/immunology , Signal Transduction/immunology , Animals , B-Lymphocytes/physiology , Blotting, Western , DNA Primers/genetics , Endonucleases/genetics , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Fluorescence , Gene Expression Profiling , Genotype , Mice , Mice, Inbred C57BL , Mice, Knockout , Proto-Oncogene Proteins c-myc , Quantitative Trait Loci/genetics , Sialic Acid Binding Ig-like Lectin 2/genetics , Uridylate-Specific Endoribonucleases
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