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1.
Nat Immunol ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38942990

RESUMEN

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.

2.
Immunity ; 53(3): 614-626.e4, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32827457

RESUMEN

RORγt is the lineage-specific transcription factor for T helper 17 (Th17) cells whose upregulation in developing Th17 cells is critically regulated by interleukin-6 (IL-6) and TGF-ß, the molecular mechanisms of which remain largely unknown. Here we identified conserved non-coding sequences (CNSs) 6 and 9 at the Rorc gene, essential for its expression during Th17 cell differentiation but not required for RORγt expression in innate lymphocytes and γδ T cells. Mechanistically, the IL-6-signal transducer and activator of transcription 3 (STAT3) axis appeared to be largely dependent on CNS9 and only partially on CNS6 in controlling RORγt expression and epigenetic activation of the Rorc locus. TGF-ß alone was sufficient to induce RORγt expression in a CNS6- but not CNS9-dependent manner through CNS6 binding by SMAD proteins. Our study reveals an important synergistic mechanism downstream of IL-6 and TGF-ß in regulation of RORγt expression and Th17 cell commitment via distinct cis-regulatory elements.


Asunto(s)
Interleucina-6/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/biosíntesis , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Células Th17/citología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Regulación de la Expresión Génica/genética , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Factor de Transcripción STAT3/metabolismo , Células Th17/inmunología
3.
Nucleic Acids Res ; 52(9): 4935-4949, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38421638

RESUMEN

TGF-ß signaling family plays an essential role to regulate fate decisions in pluripotency and lineage specification. How the action of TGF-ß family signaling is intrinsically executed remains not fully elucidated. Here, we show that HBO1, a MYST histone acetyltransferase (HAT) is an essential cell intrinsic determinant for TGF-ß signaling in human embryonic stem cells (hESCs). HBO1-/- hESCs fail to response to TGF-ß signaling to maintain pluripotency and spontaneously differentiate into neuroectoderm. Moreover, HBO1 deficient hESCs show complete defect in mesendoderm specification in BMP4-triggered gastruloids or teratomas. Molecularly, HBO1 interacts with SMAD4 and co-binds the open chromatin labeled by H3K14ac and H3K4me3 in undifferentiated hESCs. Upon differentiation, HBO1/SMAD4 co-bind and maintain the mesoderm genes in BMP4-triggered mesoderm cells while lose chromatin occupancy in neural cells induced by dual-SMAD inhibition. Our data reveal an essential role of HBO1, a chromatin factor to determine the action of SMAD in both human pluripotency and mesendoderm specification.


Asunto(s)
Diferenciación Celular , Histona Acetiltransferasas , Mesodermo , Transducción de Señal , Proteína Smad4 , Humanos , Proteína Morfogenética Ósea 4/metabolismo , Proteína Morfogenética Ósea 4/genética , Línea Celular , Cromatina/metabolismo , Endodermo/citología , Endodermo/metabolismo , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/genética , Histonas/metabolismo , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/citología , Mesodermo/metabolismo , Mesodermo/citología , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Proteína Smad4/metabolismo , Proteína Smad4/genética , Factor de Crecimiento Transformador beta/metabolismo
4.
Proc Natl Acad Sci U S A ; 120(19): e2221440120, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-37126706

RESUMEN

Geraniol derived from essential oils of various plant species is widely used in the cosmetic and perfume industries. It is also an essential trait of the pleasant smell of rose flowers. In contrast to other monoterpenes which are produced in plastids via the methyl erythritol phosphate pathway, geraniol biosynthesis in roses relies on cytosolic NUDX1 hydrolase which dephosphorylates geranyl diphosphate (GPP). However, the metabolic origin of cytosolic GPP remains unknown. By feeding Rosa chinensis "Old Blush" flowers with pathway-specific precursors and inhibitors, combined with metabolic profiling and functional characterization of enzymes in vitro and in planta, we show that geraniol is synthesized through the cytosolic mevalonate (MVA) pathway by a bifunctional geranyl/farnesyl diphosphate synthase, RcG/FPPS1, producing both GPP and farnesyl diphosphate (FPP). The downregulation and overexpression of RcG/FPPS1 in rose petals affected not only geraniol and germacrene D emissions but also dihydro-ß-ionol, the latter due to metabolic cross talk of RcG/FPPS1-dependent isoprenoid intermediates trafficking from the cytosol to plastids. Phylogenetic analysis together with functional characterization of G/FPPS orthologs revealed that the G/FPPS activity is conserved among Rosaceae species. Site-directed mutagenesis and molecular dynamic simulations enabled to identify two conserved amino acids that evolved from ancestral FPPSs and contribute to GPP/FPP product specificity. Overall, this study elucidates the origin of the cytosolic GPP for NUDX1-dependent geraniol production, provides insights into the emergence of the RcG/FPPS1 GPPS activity from the ancestral FPPSs, and shows that RcG/FPPS1 plays a key role in the biosynthesis of volatile terpenoid compounds in rose flowers.


Asunto(s)
Geraniltranstransferasa , Rosa , Geraniltranstransferasa/genética , Ácido Mevalónico/metabolismo , Rosa/metabolismo , Citosol/metabolismo , Filogenia , Terpenos/metabolismo , Flores/metabolismo
5.
J Cell Physiol ; 239(1): 152-165, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37991435

RESUMEN

Polycomb repressive complexes (PRCs) play critical roles in cell fate decisions during normal development as well as disease progression through mediating histone modifications such as H3K27me3 and H2AK119ub. How exactly PRCs recruited to chromatin remains to be fully illuminated. Here, we report that YTHDF1, the N6-methyladenine (m6 A) RNA reader that was previously known to be mainly cytoplasmic, associates with RNF2, a PRC1 protein that mediates H2AK119ub in human embryonic stem cells (hESCs). A portion of YTHDF1 localizes in the nuclei and associates with RNF2/H2AK119ub on a subset of gene loci related to neural development functions. Knock-down YTHDF1 attenuates H2AK119ub modification on these genes and promotes neural differentiation in hESCs. Our findings provide a noncanonical mechanism that YTHDF1 participates in PRC1 functions in hESCs.


Asunto(s)
Proteínas de Ciclo Celular , Células Madre Embrionarias Humanas , Proteínas de Unión al ARN , Humanos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina , Células Madre Embrionarias Humanas/metabolismo , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Proteínas del Grupo Polycomb/genética , Proteínas del Grupo Polycomb/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Histonas/genética , Histonas/metabolismo
6.
J Am Chem Soc ; 146(26): 17728-17737, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38899504

RESUMEN

Targeted protein degradation technology holds great potential in biomedicine, particularly in treating tumors and other protein-related diseases. Research on intracellular protein degradation using molecular glues and PROTAC technology is leading, while research on the degradation of membrane proteins and extracellular proteins through the lysosomal pathway is still in the preclinical stage. The scarcity of useful targets is an immense limitation to technological advancement, making it essential to explore novel, potentially effective approaches for targeted lysosomal degradation. Here, we employed the glucose transporter Glut1 as an innovative lysosome-targeting receptor and devised the Glut1-Facilitated Lysosomal Degradation (GFLD) strategy. We synthesized potential Glut1 ligands via reversible addition-fragmentation chain transfer (RAFT) polymerization and acquired antibody-glycooligomer conjugates through bioorthogonal reactions as lysosome-targeting protein degradation molecules, utilized in the management of PD-L1 high-expressing triple-negative breast cancer. The glucose transporter Glut1 as a lysosome-targeting receptor exhibits potential for the advancement of a broader array of medications in the future.


Asunto(s)
Transportador de Glucosa de Tipo 1 , Lisosomas , Proteolisis , Lisosomas/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Línea Celular Tumoral , Ligandos
7.
New Phytol ; 241(4): 1829-1839, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38058220

RESUMEN

The biosynthesis of specialized metabolites is strictly regulated by environmental inputs such as the day-night cycle, but the underlying mechanisms remain elusive. In Petunia hybrida cv. Mitchell flowers, the biosynthesis and emission of volatile compounds display a diurnal pattern with a peak in the evening to attract nocturnal pollinators. Using petunia flowers as a model system, we found that chromatin level regulation, especially histone acetylation, plays an essential role in mediating the day-night oscillation of the biosynthetic gene network of specialized metabolites. By performing time-course chromatin immunoprecipitation assays for histone modifications, we uncovered that a specific group of genes involved in the regulation, biosynthesis, and emission of floral volatile compounds, which displays the greatest magnitude in day-night oscillating gene expression, is associated with highly dynamic histone acetylation marks H3K9ac and H3K27ac. Specifically, the strongest oscillating genes featured a drastic removal of histone acetylation marks at night, potentially to shut down the biosynthesis of floral volatile compounds during the morning when they are not needed. Inhibiting daytime histone acetylation led to a compromised evening induction of these genes. Overall, our study suggested an active role of chromatin modification in the diurnal oscillation of specialized metabolic network.


Asunto(s)
Histonas , Petunia , Histonas/metabolismo , Acetilación , Redes y Vías Metabólicas , Procesamiento Proteico-Postraduccional , Cromatina/metabolismo , Flores/fisiología , Petunia/metabolismo , Regulación de la Expresión Génica de las Plantas
8.
FASEB J ; 37(1): e22688, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36468780

RESUMEN

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. Vasorin (VASN) has been reported to be critical in tumor development and angiogenesis. However, VASN has not been reported in CRC, and its role is unclear. In this study, VASN expression is upregulated in CRC compared with the normal tissues, and VASN expression positively correlates with N stage and poor overall survival by analysis of different datasets and 32 CRC clinicopathologic samples. Overexpression of VASN significantly promotes CRC cell progression, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while knockdown of VASN inhibits CRC progression. We found that VASN was associated with the YAP/TAZ and PI3K/AKT pathways by gene set enrichment analysis (GSEA) and gene ontology (GO) analysis. Notably, western blotting, immunofluorescence staining and co-immunofluorescence (co-IP) confirmed that VASN could interact with YAP and activate the YAP/TAZ and PTEN/PI3K/AKT pathways, and knockdown of YAP reversed this effect. Importantly, our findings indicate that VASN interacts with YAP to inhibit YAP phosphorylation and stimulates CRC proliferation, migration, and invasion through activation of the YAP/TAZ-TEAD target gene CTGF and PTEN/PI3K/AKT pathways. Our results also show that knockdown of YAP reverses the cellular phenotype induced by increased VASN. In conclusion, our study reveals that VASN acts as an oncogene to stimulate tumor progression in CRC, providing new insights into the molecular mechanisms of CRC development and representing a possible novel biomarker for CRC.


Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas c-akt , Humanos , Fosfatidilinositol 3-Quinasas , Oncogenes , Transducción de Señal , Neoplasias Colorrectales/genética , Proteínas Portadoras , Proteínas de la Membrana
9.
Biomacromolecules ; 25(3): 1671-1681, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38354397

RESUMEN

Nanoparticles (NPs) containing light-responsive polymers and imaging agents show great promise for controlled drug delivery. However, most light-responsive NPs rely on short-wavelength excitation, resulting in poor tissue penetration and potential cytotoxicity. Moreover, excessively sensitive NPs may prematurely release drugs during storage and circulation, diminishing their efficacy and causing off-target toxicity. Herein, we report visible-light-responsive NPs composed of an amphiphilic block copolymer containing responsive 4-acrylamide benzenesulfonyl azide (ABSA) and hydrophilic N,N'-dimethylacrylamide (DMA) units. The polymer pDMA-ABSA was loaded with the chemotherapy drug dasatinib and zinc tetraphenylporphyrin (ZnTPP). ZnTPP acted as an imaging reagent and a photosensitizer to reduce ABSA upon visible light irradiation, converting hydrophobic units to hydrophilic units and disrupting NPs to trigger drug release. These NPs enabled real-time fluorescence imaging in cells and exhibited synergistic chemophotodynamic therapy against multiple cancer cell lines. Our light-responsive NP platform holds great promise for controlled drug delivery and cancer theranostics, circumventing the limitations of traditional photosensitive nanosystems.


Asunto(s)
Portadores de Fármacos , Metaloporfirinas , Nanopartículas , Portadores de Fármacos/química , Azidas , Polímeros/química , Luz , Nanopartículas/química , Liberación de Fármacos
10.
BMC Anesthesiol ; 24(1): 14, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38172686

RESUMEN

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain. METHODS: This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events. RESULTS: In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method. CONCLUSIONS: Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS. TRIAL REGISTRATION: The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).


Asunto(s)
Acetaminofén , Bloqueo Nervioso , Humanos , Acetaminofén/uso terapéutico , Cirugía Torácica Asistida por Video/métodos , Sufentanilo , Oxicodona , Estudios Prospectivos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Analgésicos/uso terapéutico , Analgesia Controlada por el Paciente/métodos , Tos , Manitol
11.
BMC Anesthesiol ; 24(1): 205, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858649

RESUMEN

BACKGROUND: Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol. METHODS: This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient's immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient's liver function and adverse events. RESULTS: Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3+, CD4+, CD8+, and NK cells and the CD4+/CD8+ ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05). CONCLUSION: The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety. TRIAL REGISTRATION: The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022).


Asunto(s)
Hemodinámica , Hepatectomía , Laparoscopía , Propofol , Humanos , Masculino , Femenino , Hepatectomía/métodos , Persona de Mediana Edad , Hemodinámica/efectos de los fármacos , Laparoscopía/métodos , Propofol/administración & dosificación , Propofol/farmacología , Benzodiazepinas/administración & dosificación , Anestésicos Intravenosos/farmacología , Anestésicos Intravenosos/administración & dosificación , Adulto , Anciano , Hipnóticos y Sedantes/administración & dosificación
12.
New Phytol ; 240(2): 710-726, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37547968

RESUMEN

MicroRNAs (miRNAs) play crucial roles in regulating plant development and stress responses. However, the functions and mechanism of intronic miRNAs in plants are poorly understood. This study reports a stress-responsive RNA splicing mechanism for intronic miR400 production, whereby miR400 modulates reactive oxygen species (ROS) accumulation and improves plant tolerance by downregulating its target expression. To monitor the intron splicing events, we used an intronic miR400 splicing-dependent luciferase transgenic line. Luciferase activity was observed to decrease after high cadmium concentration treatment due to the retention of the miR400-containing intron, which inhibited the production of mature miR400. Furthermore, we demonstrated that under Cd treatments, Pentatricopeptide Repeat Protein 1 (PPR1), the target of miR400, acts as a positive regulator by inducing ROS accumulation. Ppr1 mutation affected the Complex III activity in the electron transport chain and RNA editing of the mitochondrial gene ccmB. This study illustrates intron splicing as a key step in intronic miR400 production and highlights the function of intronic miRNAs as a 'signal transducer' in enhancing plant stress tolerance.


Asunto(s)
Arabidopsis , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Arabidopsis/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Intrones/genética , Empalme del ARN/genética , Regulación de la Expresión Génica de las Plantas
13.
J Med Virol ; 95(2): e28516, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36680413

RESUMEN

In China, most SARS-CoV-2-infected individuals had been vaccinated with inactivated vaccines. However, little is known about their immune resistances to the previous variants of concerns (VOCs) and the current Omicron sublineages. Here, we collected convalescent serum samples from SARS-CoV-2-infected individuals during the ancestral, Delta, and Omicron BA.1 waves, and evaluated their cross-neutralizing antibodies (nAbs) against the previous VOCs and the current Omicron sublineages using VSV-based pseudoviruses. In the convalescents who had been unvaccinated and vaccinated with two doses of inactivated vaccines, we found infections from either the ancestral or the Delta strain elicited moderate cross-nAbs to previous VOCs, but very few cross-nAbs to the Omicron sublineages, including BA.1, BA.2, BA.3, and BA.4/5. The individuals who had been vaccinated with two doses of inactivated vaccines before Omicron BA.1 infection had moderate nAbs to Omicron BA.1, but weak cross-nAbs to the other Omicron sublineages. While three doses of inactivated vaccines followed Omicron BA.1 infection induced elevated and still weak cross-nAbs to other Omicron sublineages. Our results indicate that the Omicron sublineages show significant immune escape in the previously SARS-CoV-2-infected individuals and thus highlights the importance of vaccine boosters in this population.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Vacunas de Productos Inactivados , Sueroterapia para COVID-19 , Anticuerpos Neutralizantes , Anticuerpos Antivirales
14.
Pestic Biochem Physiol ; 192: 105419, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37105625

RESUMEN

Glyphosate is an herbicide commonly used in agriculture, and its widespread use has adversely affected the survival of nontarget organisms. Among these organisms, bees in particular are important pollinators, and declining bee populations have severely affected crop yields around the world. However, the molecular mechanism by which glyphosate harms bees remains unclear. In our experiment, we screened and cloned a glyphosate-induced gene in Apis cerana cerana (A. c. cerana) and named glyphosate response factor 1 (AccGRF1). Sequence analysis showed that AccGRF1 contains a winged-helix DNA binding domain, which suggests that it belongs to the Forkhead box (Fox) protein family. qRT-PCR and heterologous expression in Escherichia coli and yeast showed that AccGRF1 can respond to glyphosate and oxidative stress. After AccGRF1 knockdown by means of RNA interference (RNAi), the resistance of A. c. cerana to glyphosate stress improved. The results suggested that AccGRF1 is involved in A. c. cerana glyphosate stress tolerance. This study reveals the functions of Fox transcription factors in response to glyphosate stress and provides molecular insights into the regulation of glyphosate responses in honeybees.


Asunto(s)
Glicina , Estrés Oxidativo , Abejas/genética , Animales , Estrés Oxidativo/genética , Interferencia de ARN , Glicina/toxicidad , Proteínas de Insectos/metabolismo , Glifosato
15.
J Appl Clin Med Phys ; 24(1): e13806, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36347055

RESUMEN

PURPOSE: This manuscript describes the structure, management and outcomes of a multi-institutional clinical and research medical physics residency program (Harvard Medical Physics Residency Program, or HMPRP) to provide potentially useful information to the centers considering a multi-institutional approach for their training programs. METHODS: Data from the program documents and public records was used to describe HMPRP and obtain statistics about participating faculty, enrolled residents, and graduates. Challenges associated with forming and managing a multi-institutional program and developed solutions for effective coordination between several clinical centers are described. RESULTS: HMPRP was formed in 2009 and was accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP) in 2011. It is a 3-year therapy program, with a dedicated year of research and the 2 years of clinical training at three academic hospitals. A CAMPEP-accredited Certificate Program is embedded in HMPRP to allow enrolled residents to complete a formal didactic training in medical physics if necessary. The clinical training covers the material required by CAMPEP. In addition, training in protons, CyberKnife, MR-linac, and at network locations is included. The clinical training and academic record of the residents is outstanding. All graduates have found employment within clinical medical physics, mostly at large academic centers and graduates had a 100% pass rate at the oral American Board of Radiology exams. On average, three manuscripts per resident are published during residency, and multiple abstracts are presented at conferences. CONCLUSIONS: A multi-institutional medical physics residency program can be successfully formed and managed. With a collaborative administrative structure, the program creates an environment for high-quality clinical training of the residents and high productivity in research. The main advantage of such program is access to a wide variety of resources. The main challenge is creating a structure for efficient management of multiple resources at different locations. This report may provide valuable information to centers considering starting a multi-institutional residency program.


Asunto(s)
Internado y Residencia , Humanos , Estados Unidos , Educación de Postgrado en Medicina , Acreditación , Física Sanitaria/educación , Instituciones de Salud
16.
Plant J ; 108(3): 737-751, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34403557

RESUMEN

Out of the three aromatic amino acids, the highest flux in plants is directed towards phenylalanine, which is utilized to synthesize proteins and thousands of phenolic metabolites contributing to plant fitness. Phenylalanine is produced predominantly in plastids via the shikimate pathway and subsequent arogenate pathway, both of which are subject to complex transcriptional and post-transcriptional regulation. Previously, it was shown that allosteric feedback inhibition of arogenate dehydratase (ADT), which catalyzes the final step of the arogenate pathway, restricts flux through phenylalanine biosynthesis. Here, we show that in petunia (Petunia hybrida) flowers, which typically produce high phenylalanine levels, ADT regulation is relaxed, but not eliminated. Moderate expression of a feedback-insensitive ADT increased flux towards phenylalanine, while high overexpression paradoxically reduced phenylalanine formation. This reduction could be partially, but not fully, recovered by bypassing other known metabolic flux control points in the aromatic amino acid network. Using comparative transcriptomics, reverse genetics, and metabolic flux analysis, we discovered that transcriptional regulation of the d-ribulose-5-phosphate 3-epimerase gene in the pentose phosphate pathway controls flux into the shikimate pathway. Taken together, our findings reveal that regulation within and upstream of the shikimate pathway shares control over phenylalanine biosynthesis in the plant cell.


Asunto(s)
Hidroliasas/genética , Petunia/genética , Petunia/metabolismo , Fenilalanina/biosíntesis , Proteínas de Plantas/genética , Carbohidrato Epimerasas/genética , Carbohidrato Epimerasas/metabolismo , Flores/genética , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas , Hidroliasas/metabolismo , Mutación , Fenilalanina/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Plastidios/genética , Plastidios/metabolismo , Metabolismo Secundario/genética , Ácido Shikímico/metabolismo
17.
J Exp Bot ; 73(2): 555-570, 2022 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-34129033

RESUMEN

Galling insects gain food and shelter by inducing specialized anatomical structures in their plant hosts. Such galls often accumulate plant defensive metabolites protecting the inhabiting insects from predation. We previously found that, despite a marked natural chemopolymorphism in natural populations of Pistacia palaestina, the monoterpene content in Baizongia pistaciae-induced galls is substantially higher than in leaves of their hosts. Here we show a general up-regulation of key structural genes in both the plastidial and cytosolic terpene biosynthetic pathways in galls as compared with non-colonized leaves. Novel prenyltransferases and terpene synthases were functionally expressed in Escherichia coli to reveal their biochemical function. Individual Pistacia trees exhibiting chemopolymorphism in terpene compositions displayed differential up-regulation of selected terpene synthase genes, and the metabolites generated by their gene products in vitro corresponded to the monoterpenes accumulated by each tree. Our results delineate molecular mechanisms responsible for the formation of enhanced monoterpene in galls and the observed intraspecific monoterpene chemodiversity displayed in P. palaestina. We demonstrate that gall-inhabiting aphids transcriptionally reprogram their host terpene pathways by up-regulating tree-specific genes, boosting the accumulation of plant defensive compounds for the protection of colonizing insects.


Asunto(s)
Áfidos , Pistacia , Animales , Tumores de Planta , Terpenos , Regulación hacia Arriba
18.
Plant Cell ; 31(12): 2996-3014, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31604812

RESUMEN

The conversion of etioplasts into chloroplasts in germinating cotyledons is a crucial transition for higher plants, enabling photoautotrophic growth upon illumination. Tight coordination of chlorophyll biosynthesis and photosynthetic complex assembly is critical for this process. ORANGE (OR), a DnaJ-like zinc finger domain-containing protein, was reported to trigger the biogenesis of carotenoid-accumulating plastids by promoting carotenoid biosynthesis and sequestration. Both nuclear and plastidic localizations of OR have been observed. Here, we show that Arabidopsis (Arabidopsis thaliana) OR physically interacts with the transcription factor TCP14 in the nucleus and represses its transactivation activity. Through this interaction, the nucleus-localized OR negatively regulates expression of EARLY LIGHT-INDUCIBLE PROTEINS (ELIPs), reduces chlorophyll biosynthesis, and delays development of thylakoid membranes in the plastids of germinating cotyledons. Nuclear abundance of OR decreased upon illumination. Together with an accumulation of TCP14 in the nucleus, this derepresses chloroplast biogenesis during de-etiolation. TCP14 is epistatic to OR and expression of ELIPs is directly regulated by the binding of TCP14 to Up1 elements in the ELIP promoter regions. Our results demonstrate that the interaction between OR and TCP14 in the nucleus leads to repression of chloroplast biogenesis in etiolated seedlings and provide new insights into the regulation of early chloroplast development.plantcell;31/12/2996/FX1F1fx1.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Clorofila/biosíntesis , Cloroplastos/metabolismo , Cotiledón/metabolismo , Proteínas del Choque Térmico HSP40/metabolismo , Factores de Transcripción/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/efectos de la radiación , Núcleo Celular/metabolismo , Núcleo Celular/efectos de la radiación , Cotiledón/genética , Etiolado , Regulación de la Expresión Génica de las Plantas/genética , Germinación , Proteínas del Choque Térmico HSP40/genética , Proteínas del Choque Térmico HSP40/efectos de la radiación , Iluminación , Plastidios/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Plantones/metabolismo , Tilacoides/metabolismo , Factores de Transcripción/genética , Regulación hacia Arriba
19.
Opt Lett ; 47(7): 1754-1757, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35363727

RESUMEN

We experimentally investigate image reconstruction through a scattering medium under white-light illumination. To solve the inverse problem of noninvasive scattering imaging, a modified iterative algorithm is employed with an interpretable constraint on the optical transfer function (OTF). As a result, a sparse and real object can be retrieved whether it is illuminated with a narrowband or broadband light. Compared with the well-known speckle correlation technique (SCT), the proposed method requires no restrictions on the speckle autocorrelation and shows a potential advantage in scattering imaging.

20.
Opt Lett ; 47(8): 2032-2035, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35427329

RESUMEN

A kind of plasmonic nanostructure is proposed that can generate the arbitrary superposition of orbital angular momentum (OAM) states in surface plasmons (SPs), which is achieved by combining the segmented spirals with nanoslit pairs. The structures can independently modulate both the phase and amplitude of SP waves, and thus enable the superposition of two OAM states with arbitrary topological charges (TCs) as well as free control of their relative amplitudes. Superposed states distributed over the entire Bloch sphere and hybrid superposed states with different TCs were constructed and experimentally demonstrated. This work will offer more opportunities for multifunctional plasmonic devices.

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