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1.
mBio ; 11(2)2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127451

RESUMO

Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneumocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. carinii from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology.IMPORTANCE Pneumocystis continues to be a major cause of disease in humans with immunodeficiency, especially those with HIV/AIDS and organ transplants, and is being seen with increasing frequency worldwide in patients treated with immunodepleting monoclonal antibodies. Annual health care associated with Pneumocystis pneumonia costs ∼$475 million dollars in the United States alone. In addition to causing overt disease in immunodeficient individuals, Pneumocystis can cause subclinical infection or colonization in healthy individuals, which may play an important role in species preservation and disease transmission. Our work sheds new light on the diversity and complexity of the msg superfamily and strongly suggests that the versatility of this superfamily reflects multiple functions, including antigenic variation to allow immune evasion and optimal adaptation to host environmental conditions to promote efficient infection and transmission. These findings are essential to consider in developing new diagnostic and therapeutic strategies.

2.
Viruses ; 12(2)2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32102240

RESUMO

Infectious bursal disease (IBD) is an immunosuppressive, highly contagious, and lethal disease of young chickens caused by IBD virus (IBDV). It results in huge economic loss to the poultry industry worldwide. Infection caused by very virulent IBDV (vvIBDV) strains results in high mortality in young chicken flocks. However, the replication characteristics of vvIBDV are not well studied. Publications have shown that virus protein 3 (VP3) binds to VP1 and viral double-stranded RNA, and together they form a ribonucleoprotein complex that plays a key role in virus replication. In this study, vvIBDV VP3 was used to identify host proteins potentially involved in modulating vvIBDV replication. Chicken eukaryotic translation elongation factor 1α (cheEF1α) was chosen to further investigate effects on vvIBDV replication. By small interfering RNA-mediated cheEF1α knockdown, we demonstrated the possibility of significantly reducing viral polymerase activity, with a subsequent reduction in virus yields. Conversely, over-expression of cheEF1α significantly increased viral polymerase activity and virus replication. Further study confirmed that cheEF1α interacted only with vvIBDV VP3 but not with attenuated IBDV (aIBDV) VP3. Furthermore, the amino acids at the N- and C-termini were important in the interaction between vvIBDV VP3 and cheEF1α. Domain III was essential for interactions between cheEF1α and vvIBDV VP3. In summary, cheEF1α enhances vvIBDV replication by promoting the activity of virus polymerase. Our study indicates cheEF1α is a potential target for limiting vvIBDV infection.

3.
J Clin Invest ; 130(3): 1233-1251, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32039915

RESUMO

Smooth muscle cell (SMC) proliferation has been thought to limit the progression of thoracic aortic aneurysm and dissection (TAAD) because loss of medial cells associates with advanced disease. We investigated effects of SMC proliferation in the aortic media by conditional disruption of Tsc1, which hyperactivates mTOR complex 1. Consequent SMC hyperplasia led to progressive medial degeneration and TAAD. In addition to diminished contractile and synthetic functions, fate-mapped SMCs displayed increased proteolysis, endocytosis, phagocytosis, and lysosomal clearance of extracellular matrix and apoptotic cells. SMCs acquired a limited repertoire of macrophage markers and functions via biogenesis of degradative organelles through an mTOR/ß-catenin/MITF-dependent pathway, but were distinguishable from conventional macrophages by an absence of hematopoietic lineage markers and certain immune effectors even in the context of hyperlipidemia. Similar mTOR activation and induction of a degradative SMC phenotype in a model of mild TAAD due to Fbn1 mutation greatly worsened disease with near-uniform lethality. The finding of increased lysosomal markers in medial SMCs from clinical TAAD specimens with hyperplasia and matrix degradation further supports the concept that proliferation of degradative SMCs within the media causes aortic disease, thus identifying mTOR-dependent phenotypic modulation as a therapeutic target for combating TAAD.

4.
ACS Nano ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31944096

RESUMO

MoS2 holds great promise as a cost-effective alternative to Pt for catalyzing the hydrogen evolution reaction (HER) of water, but its reported catalytic efficiency is still worse than that of Pt, the best HER catalyst but too rare and expensive for mass production of hydrogen. We report a strategy to enable the catalytic activity of monolayer MoS2 films that are even better than that of Pt via engineering the interaction of the monolayer with supporting substrates. The monolayer films were grown with chemical vapor deposition processes and controlled to have an optimal density (7-10%) of sulfur vacancies. We find that the catalytic activity of MoS2 can be affected by substrates in two ways: forming an interfacial tunneling barrier with MoS2 and modifying the chemical nature of MoS2 via charge transfer (proximity doping). Following this understanding, we enable excellent catalytic activities at the monolayer MoS2 films by using substrates that can provide n-doping to MoS2 and form low interfacial tunneling barriers with MoS2, such as Ti. The catalytic performance may be further boosted to be even better than Pt by crumpling the films on Ti coated flexible polymer substrates, as the Tafel slope of the film is substantially decreased with the presence of crumpling-induced compressive strain. The monolayer MoS2 films show no degradation in catalytic performance after being continuously tested for over 2 months.

5.
J Virol ; 94(2)2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31666381

RESUMO

Infectious bursal disease virus (IBDV) is an important member of the Birnaviridae family, causing severe immunosuppressive disease in chickens. The major capsid protein VP2 is responsible for the binding of IBDV to the host cell and its cellular tropism. In order to find proteins that potentially interact with IBDV VP2, a liquid chromatography-mass spectrometry (LC-MS) assay was conducted, and the host chicken CD74 protein was identified. Here, we investigate the role of chicken CD74 in IBDV attachment. Coimmunoprecipitation assays indicated that the extracellular domain of CD74 interacted with the VP2 proteins of multiple IBDV strains. Knockdown and overexpression experiments showed that CD74 promotes viral infectivity. Confocal assays showed that CD74 overexpression allows the attachment of IBDV and subvirus-like particles (SVPs) to the cell surface of nonpermissive cells, and quantitative PCR (qPCR) analysis further confirmed the attachment function of CD74. Anti-CD74 antibody, soluble CD74, depletion of CD74 by small interfering RNA (siRNA), and CD74 knockdown in the IBDV-susceptible DT40 cell line significantly inhibited IBDV binding, suggesting a pivotal role of this protein in virus attachment. These findings demonstrate that CD74 is a novel important receptor for IBDV attachment to the chicken B lymphocyte cell line DT40.IMPORTANCE CD74 plays a pivotal role in the correct folding and functional stability of major histocompatibility complex class II (MHC-II) molecules and in the presentation of antigenic peptides, acting as a regulatory factor in the antigen presentation process. In our study, we demonstrate a novel role of CD74 during IBDV infection, showing that chicken CD74 plays a significant role in IBDV binding to target B cells by interacting with the viral VP2 protein. This is the first report demonstrating that CD74 is involved as a novel attachment receptor in the IBDV life cycle in target B cells, thus contributing new insight into host-pathogen interactions.

6.
Environ Pollut ; 246: 381-389, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30577006

RESUMO

Heavy metals and emerging engineered nanoparticles (ENPs) are two current environmental concerns that have attracted considerable attention. Cerium oxide nanoparticles (CeO2NPs) are now used in a plethora of industrial products, while cadmium (Cd) is a great environmental concern because of its toxicity to animals and humans. Up to now, the interactions between heavy metals, nanoparticles and plants have not been extensively studied. The main objectives of this study were (i) to determine the synergistic effects of Cd and CeO2NPs on the physiological parameters of Brassica and their accumulation in plant tissues and (ii) to explore the underlying physiological/phenotypical effects that drive these specific changes in plant accumulation using Artificial Neural Network (ANN) as an alternative methodology to modeling and simulating plant uptake of Ce and Cd. The combinations of three cadmium levels (0 [control] and 0.25 and 1 mg/kg of dry soil) and two CeO2NPs concentrations (0 [control] and 500 mg/kg of dry soil) were investigated. The results showed high interactions of co-existing CeO2NPs and Cd on plant uptake of these metal elements and their interactive effects on plant physiology. ANN also identified key physiological factors affecting plant uptake of co-occurring Cd and CeO2NPs. Specifically, the results showed that root fresh weight and the net photosynthesis rate are parameters governing Ce uptake in plant leaves and roots while root fresh weight and Fv/Fm ratio are parameters affecting Cd uptake in leaves and roots. Overall, ANN is a capable approach to model plant uptake of co-occurring CeO2NPs and Cd.


Assuntos
Brassica napus/fisiologia , Cádmio/metabolismo , Cério/metabolismo , Poluentes do Solo/metabolismo , Brassica napus/efeitos dos fármacos , Brassica napus/metabolismo , Cádmio/farmacologia , Cério/farmacologia , Humanos , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Fotossíntese/fisiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/fisiologia , Solo/química , Poluentes do Solo/farmacologia
7.
Int J Ophthalmol ; 11(12): 1916-1921, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588422

RESUMO

AIM: To recombine the human alpha B-crystallin (αB-crystallin) using gene cloning technology and prokaryotic expression vector and confirm the biological activity of recombinant human αB-crystallin. METHODS: Cloning the human αB-crystallin cDNA according to the nucleotide sequence of the human αB-crystallin, constructing the pET-28/CRYAB prokaryotic expression plasmid by restriction enzyme digestion method, and stably expressing transformed into the Escherichia coli (E. coli) DH5 alpha. The recombinant human αB-crystallin was purified by Q sepharose. By enzyme digestion analysis, Western blotting and sequencing, the recombinant human αB-crystallin was identified and the activity of its molecular protein was detected. RESULTS: Compared with the gene bank (GeneBank), the cloned human sequence of human αB-crystallin cDNA has the same open reading frame. Identification and sequencing of the cloned human αB-crystallin cDNA in prokaryotic expression vector confirmed the full length sequence, and the vector was constructed successfully. The E. coli containing plasmid pET-28/CRYAB induced by isopropyl-ß-D-thiogalactoside successfully expressed the human αB-crystallin. Insulin confirmed that the recombinant human αB-crystallin has a molecular chaperone activity. CONCLUSION: The prokaryotic expression vector pET-28/CRYAB of recombinant human αB-crystallin is successfully constructed, and the recombinant human αB-crystallin with molecular chaperone activity is obtained, which lay a foundation for the research and application of the recombinant human αB-crystallin and its chaperone activity.

8.
Materials (Basel) ; 11(11)2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30405040

RESUMO

The effects of fluorine (F) doping on the phase, crystal structure, and electrochemical performance of Na2Ti3O7 are studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), and electrochemical measurements. F-doping does not change the crystal structure of NTO, although it has an effect on the morphology of the resultant product. As an anode material for sodium-ion batteries, the specific capacity of Na2Ti3O7 exhibits a 30% increase with F-doping owing to the improved sodium ion diffusion coefficient. F-doped Na2Ti3O7 also displays an enhanced rate capability and favourable cycling performance for more than 800 cycles.

9.
Mol Ther Nucleic Acids ; 12: 184-194, 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30195757

RESUMO

The pediatric T cell acute lymphoblastic leukemia (T-ALL) still remains a cancer with worst prognosis for high recurrence. Massive studies were conducted for the leukemia relapse based on diagnosis and relapse paired samples. However, the initially diagnostic samples may contain the relapse information and mechanism, which were rarely studied. In this study, we collected mRNA and microRNA (miRNA) data from initially diagnosed pediatric T-ALL samples with their relapse or remission status after treatment. Integrated differential co-expression and miRNA-transcription factor (TF)-gene regulatory network analyses were used to reveal the possible relapse mechanisms for pediatric T-ALL. We detected miR-1246/1248 and NOTCH2 served as key nodes in the relapse network, and they combined with TF WT1/SOX4/REL to form regulatory modules that influence the progress of T-ALL. A regulatory loop miR-429-MYCN-MFHAS1 was found potentially associated with the remission of T-ALL. Furthermore, we proved miR-1246/1248 combined with NOTCH2 could promote cell proliferation in the T-ALL cell line by experiments. Meanwhile, analysis based on the miRNA-drug relationships demonstrated that drugs 5-fluorouracil, ascorbate, and trastuzumab targeting miR-1246 could serve as potential supplements for the standard therapy. In conclusion, our findings revealed the potential molecular mechanisms of T-ALL relapse by the combination of co-expression and regulatory network, and they provide preliminary clues for precise treatment of T-ALL patients.

10.
ACS Synth Biol ; 7(5): 1188-1194, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29733626

RESUMO

The dimerization and high-order oligomerization of transcription factors has endowed them with cooperative regulatory capabilities that play important roles in many cellular functions. However, such advanced regulatory capabilities have not been fully exploited in synthetic biology and genetic engineering. Here, we engineered a C-terminally fused oligomerization domain to improve the cooperativity of transcription factors. First, we found that two of three designed oligomerization domains significantly increased the cooperativity and ultrasensitivity of a transcription factor for the regulated promoter. Then, seven additional transcription factors were used to assess the modularity of the oligomerization domains, and their ultrasensitivity was generally improved, as assessed by their Hill coefficients. Moreover, we also demonstrated that the allosteric capability of the ligand-responsive domain remained intact when fusing with the designed oligomerization domain. As an example application, we showed that the engineered ultrasensitive transcription factor could be used to significantly improve the performance of a "stripe-forming" gene circuit. We envision that the oligomerization modules engineered in this study could act as a powerful tool to rapidly tune the underlying response profiles of synthetic gene circuits and metabolic pathway controllers.


Assuntos
Engenharia de Proteínas/métodos , Proteínas Recombinantes de Fusão/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação Alostérica/efeitos dos fármacos , Proteínas de Bactérias/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Proteínas de Escherichia coli/genética , Retroalimentação Fisiológica , Redes Reguladoras de Genes , Isopropiltiogalactosídeo/farmacologia , Repressores Lac/genética , Ligantes , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Regiões Promotoras Genéticas , Domínios Proteicos , Multimerização Proteica , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição/química
12.
Ophthalmic Genet ; 39(3): 300-306, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29377742

RESUMO

PURPOSE: To describe the clinical characteristics of a Chinese family with peripheral cone dystrophy (PCD) and identify the gene mutations causing PCD. METHODS: The Chinese PCD pedigree underwent comprehensive ophthalmic examinations, including visual acuity, slit lamp examination, fundoscopy, visual field examination, autofluorescence, fluorescence fundus angiography and indocyanine green angiography, full-field electroretinograms, and spectral-domain optical coherence tomography. The targeted next-generation sequencing of COD or cone-rod dystrophy (CORD) genes was used to identify the causative mutation. RESULT: The fundus characteristics of the Chinese patient were consistent with PCD. The novel compound heterozygous mutation, c.1354C>T and c.710A>G, in POC1B was identified in the patient, the mutations were segregated with the PCD phenotype in the family and were absent from ethnically matched control chromosomes. Prediction analysis demonstrated the novel missense mutation, POC1B c.710A>G, might be damaging. CONCLUSIONS: PCD was a type of COD or CORD and the novel compound heterozygous mutation in POC1B was responsible for PCD phenotype in the family.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Proteínas de Ciclo Celular/genética , Distrofias de Cones e Bastonetes/genética , Heterozigoto , Mutação , Retinite Pigmentosa/genética , Adulto , Feminino , Humanos , Masculino , Linhagem
13.
G3 (Bethesda) ; 8(2): 505-518, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29196496

RESUMO

The successful interaction between pathogen/parasite and host requires a delicate balance between fitness of the former and survival of the latter. To optimize fitness a parasite/pathogen must effectively create an environment conducive to reproductive success, while simultaneously avoiding or minimizing detrimental host defense response. The association between Microbotryum lychnidis-dioicae and its host Silene latifolia serves as an excellent model to examine such interactions. This fungus is part of a species complex that infects species of the Caryophyllaceae, replacing pollen with the fungal spores. In the current study, transcriptome analyses of the fungus and its host were conducted during discrete stages of bud development so as to identify changes in fungal gene expression that lead to spore development and to identify changes associated with infection in the host plant. In contrast to early biotrophic phase stages of infection for the fungus, the latter stages involve tissue necrosis and in the case of infected female flowers, further changes in the developmental program in which the ovary aborts and a pseudoanther is produced. Transcriptome analysis via Illumina RNA sequencing revealed enrichment of fungal genes encoding small secreted proteins, with hallmarks of effectors and genes found to be relatively unique to the Microbotryum species complex. Host gene expression analyses also identified interesting sets of genes up-regulated, including those involving stress response, host defense response, and several agamous-like MADS-box genes (AGL61 and AGL80), predicted to interact and be involved in male gametophyte development.


Assuntos
Basidiomycota/genética , Doenças das Plantas/genética , Pólen/genética , Silene/genética , Basidiomycota/fisiologia , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Regulação Fúngica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/microbiologia , Pólen/microbiologia , Silene/microbiologia
14.
Nat Commun ; 8(1): 2149, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29247167

RESUMO

Establishment of a functional vascular network is rate-limiting in embryonic development, tissue repair and engineering. During blood vessel formation, newly generated endothelial cells rapidly expand into primitive plexi that undergo vascular remodeling into circulatory networks, requiring coordinated growth inhibition and arterial-venous specification. Whether the mechanisms controlling endothelial cell cycle arrest and acquisition of specialized phenotypes are interdependent is unknown. Here we demonstrate that fluid shear stress, at arterial flow magnitudes, maximally activates NOTCH signaling, which upregulates GJA4 (commonly, Cx37) and downstream cell cycle inhibitor CDKN1B (p27). Blockade of any of these steps causes hyperproliferation and loss of arterial specification. Re-expression of GJA4 or CDKN1B, or chemical cell cycle inhibition, restores endothelial growth control and arterial gene expression. Thus, we elucidate a mechanochemical pathway in which arterial shear activates a NOTCH-GJA4-CDKN1B axis that promotes endothelial cell cycle arrest to enable arterial gene expression. These insights will guide vascular regeneration and engineering.


Assuntos
Pontos de Checagem do Ciclo Celular/genética , Conexinas/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Receptor Notch1/genética , Animais , Artérias/metabolismo , Artérias/fisiologia , Células Cultivadas , Conexinas/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Feminino , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Fisiológica/genética , Receptor Notch1/metabolismo , Estresse Mecânico
15.
J Phys Chem Lett ; 8(18): 4479-4485, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28857560

RESUMO

To describe static correlation, we develop a new approach to density functional theory (DFT), which uses a generalized auxiliary system that is of a different symmetry, such as particle number or spin, from that of the physical system. The total energy of the physical system consists of two parts: the energy of the auxiliary system, which is determined with a chosen density functional approximation (DFA), and the excitation energy from an approximate linear response theory that restores the symmetry to that of the physical system, thus rigorously leading to a multideterminant description of the physical system. The electron density of the physical system is different from that of the auxiliary system and is uniquely determined from the functional derivative of the total energy with respect to the external potential. Our energy functional is thus an implicit functional of the physical system density, but an explicit functional of the auxiliary system density. We show that the total energy minimum and stationary states, describing the ground and excited states of the physical system, can be obtained by a self-consistent optimization with respect to the explicit variable, the generalized Kohn-Sham noninteracting density matrix. We have developed the generalized optimized effective potential method for the self-consistent optimization. Among options of the auxiliary system and the associated linear response theory, reformulated versions of the particle-particle random phase approximation (pp-RPA) and the spin-flip time-dependent density functional theory (SF-TDDFT) are selected for illustration of principle. Numerical results show that our multireference DFT successfully describes static correlation in bond dissociation and double bond rotation.

16.
J Phys Chem Lett ; 8(19): 4746-4751, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28895734

RESUMO

A new self-consistent procedure for calculating the total energy with an orbital-dependent density functional approximation (DFA), the generalized optimized effective potential (GOEP), is developed in the present work. The GOEP is a nonlocal Hermitian potential that delivers the sets of occupied and virtual orbitals and minimizes the total energy. The GOEP optimization leads to the same minimum as does the orbital optimization. The GOEP method is promising as an effective optimization approach for orbital-dependent functionals, as demonstrated for the self-consistent calculations of the random phase approximation (RPA) to the correlation functionals in the particle-hole (ph) and particle-particle (pp) channels. The results show that the accuracy in describing the weakly interacting van der Waals systems is significantly improved in the self-consistent calculations. In particular, the important single excitations contribution in non-self-consistent RPA calculations can be captured self-consistently through the GOEP optimization, leading to orbital renormalization, without using the single excitations in the energy functional.

17.
Nature ; 545(7653): 224-228, 2017 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-28467822

RESUMO

Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism, little is understood about the role of fibroblast growth factors (FGFs) in this context. Here we identify FGF receptor (FGFR) signalling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signalling inputs results in decreased glycolysis, leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/Fgfr3 double mutant mice, while HK2 overexpression partly rescues the defects caused by suppression of FGF signalling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development.


Assuntos
Células Endoteliais/citologia , Células Endoteliais/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Glicólise , Neovascularização Fisiológica , Transdução de Sinais , Animais , Movimento Celular , Proliferação de Células , Feminino , Hexoquinase/metabolismo , Linfangiogênese , Vasos Linfáticos/citologia , Vasos Linfáticos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/deficiência , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/deficiência , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo
18.
Microbiology ; 163(3): 410-420, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28100297

RESUMO

Microbotryum lychnidis-dioicae is an obligate biotrophic parasite of the wildflower species Silene latifolia. This dikaryotic fungus, commonly known as an anther smut, requires that haploid, yeast-like sporidia of opposite mating types fuse and differentiate into dikaryotic hyphae that penetrate host tissue as part of the fungal life cycle. Mating occurs under conditions of cool temperatures and limited nutrients. Further development requires host cues or chemical mimics, including a variety of lipids, e.g. phytols. To identify global changes in transcription associated with developmental shifts, RNA-Seq was conducted at several in vitro stages of fungal propagation, i.e. haploid cells grown independently on rich and nutrient-limited media, mated cells on nutrient-limited media as well as a time course of such mated cells exposed to phytol. Comparison of haploid cells grown under rich and nutrient-limited conditions identified classes of genes probably associated with general nutrient availability, including components of the RNAi machinery. Some gene enrichment patterns comparing the nutrient-limited and mated transcriptomes suggested gene expression changes associated with the mating programme (e.g. homeodomain binding proteins, secreted proteins, proteins unique to M. lychnidis-dioicae¸ multicopper oxidases and RhoGEFs). Analysis for phytol treatment compared with mated cells alone allowed identification of genes likely to be involved in the dikaryotic switch (e.g. oligopeptide transporters). Gene categories of particular note in all three conditions included those in the major facilitator superfamily, proteins containing PFAM domains of the secretory lipase family as well as proteins predicted to be secreted, many of which have the hallmarks of fungal effectors with potential roles in pathogenicity.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(5): 1495-1499, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-27784381

RESUMO

OBJECTIVE: To analyze the clinical characteristics, diagonsis and treatment of patients with hemophilia in Gansu province of China. METHODS: The clinical data of 223 cases of hemophilia in our center between January 2010 and May 2015 were collected and analyzed retrospectively, these 223 cases of hemophilia were from 14 cities in Gansu and neighboring provinces, including 203 cases of hemophili A (HA) and 20 cases of hemophili B (HB), among them 222 cases were male, only 1 female(HA), 177 cases were from Rural areas (79.4%). RESULTS: The median age of first bleeding was 2 years old, and the average age of confirmed as hemophilia was 5.6±6.5 years, the delayed time of diagnoses of HA and HB was 2.50±4.91 and 2.07±4.76 years, respetively, among all the patients 168 caese complicated with joint hemorrhage (75.3%), 123 cases with joint deformities (55.2%). 91.6% of the patients were treated according to demand, the HBV and HCV infection rates were 1.7% and 6.2% respectively. The first-visited hospital of 86.9% patients was hospitalized below 3 grade of level, only 15.9% of these patients were considered to diagnose as hemophili. CONCLUSION: The accurate level of diagnosis rate for hemophiliacs in Gansu province is low, the delay time of diagnosis is longer, the ratios of complicated joint hemorrhage, total accumulative joint deformity were high, HCV infection rate is also high.


Assuntos
Hemofilia A , Hemorragia , Pré-Escolar , China , Feminino , Humanos , Masculino , Estudos Retrospectivos
20.
Genome Announc ; 4(4)2016 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-27540072

RESUMO

Spizellomyces punctatus is a basally branching chytrid fungus that is found in the Chytridiomycota phylum. Spizellomyces species are common in soil and of importance in terrestrial ecosystems. Here, we report the genome sequence of S. punctatus, which will facilitate the study of this group of early diverging fungi.

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