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1.
J Med Chem ; 64(15): 10951-10966, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34260245

RESUMO

Influenza viruses cause approximately half a million deaths every year worldwide. Vaccines are available but partially effective, and the number of antiviral medications is limited. Thus, it is crucial to develop therapeutic strategies to counteract this major pathogen. Influenza viruses enter the host cell via their hemagglutinin (HA) proteins. The HA subtypes of influenza A virus are phylogenetically classified into groups 1 and 2. Here, we identified an inhibitor of the HA protein, a tertiary aryl sulfonamide, that prevents influenza virus entry and replication. This compound shows potent antiviral activity against diverse H1N1, H5N1, and H3N2 influenza viruses encoding HA proteins from both groups 1 and 2. Synthesis of derivatives of this aryl sulfonamide identified moieties important for antiviral activity. This compound may be considered as a lead for drug development with the intent to be used alone or in combination with other influenza A virus antivirals to enhance pan-subtype efficacy.


Assuntos
Antivirais/farmacologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A/efeitos dos fármacos , Sulfonamidas/farmacologia , Antivirais/síntese química , Antivirais/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
2.
Ann Vasc Surg ; 72: 666.e1-666.e6, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33227466

RESUMO

Case of extrahepatic portovenous obstruction (EHPVO) with giant splenic artery aneurysm and concomitant hypersplenism. The presence of bicytopenia and venous collaterals around the giant splenic aneurysm made splenectomy risky, and endovascular trapping of the giant aneurysm with partial splenic embolization was planned. Due to high flow, intraprocedural crossing of the giant aneurysm was not possible, and large coils were unstable. The aneurysm was successfully embolized with liquid embolic glue: lipiodol 50% mixture. Although the patient did not have septic complications despite large splenic infarct, the patient had secondary thrombocytosis leading to significant thrombotic complications akin to postsplenectomy syndrome. These were all successfully managed medically, and splenectomy was avoided.


Assuntos
Aneurisma/terapia , Embolização Terapêutica , Procedimentos Endovasculares , Hiperesplenismo/etiologia , Hipertensão Portal/etiologia , Veia Porta , Artéria Esplênica , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Embolização Terapêutica/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Hiperesplenismo/diagnóstico por imagem , Hipertensão Portal/diagnóstico , Hipertensão Portal/fisiopatologia , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Artéria Esplênica/diagnóstico por imagem , Trombocitose/etiologia , Resultado do Tratamento
3.
Elife ; 92020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33269701

RESUMO

Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here, we show that infection of human lung epithelial cells with influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. Although these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, in several cases, specific inhibition of the IAV-induced splicing pattern also attenuates viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein required for efficient splicing of the IAV M transcript in nuclear speckles. Finally, we find an increase in hnRNP K in nuclear speckles upon IAV infection, which may alter accessibility of hnRNP K for host transcripts thereby leading to a program of host splicing changes that promote IAV replication.


Assuntos
Processamento Alternativo , Núcleo Celular/virologia , Células Epiteliais/virologia , Vírus da Influenza A/crescimento & desenvolvimento , Pulmão/virologia , Replicação Viral , Células A549 , Núcleo Celular/genética , Núcleo Celular/metabolismo , Células Epiteliais/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/patogenicidade , Pulmão/metabolismo
4.
Nat Commun ; 11(1): 4577, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32917881

RESUMO

Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature and the slow turnover of NPC components complicates investigations of how individual nucleoporins act in these diverse processes. To address this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucleoporins NUP153, NUP50 and TPR. Acute depletion of TPR causes rapid and pronounced changes in transcriptomic profiles. These changes are dissimilar to shifts observed after loss of NUP153 or NUP50, but closely related to changes caused by depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, TPR depletion disrupts association of TREX-2 subunits (GANP, PCID2, ENY2) to NPCs and results in abnormal RNA transcription and export. Our findings demonstrate a unique and pivotal role of TPR in gene expression through TREX-2- and/or NXF1-dependent mRNA turnover.


Assuntos
Exodesoxirribonucleases/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Poro Nuclear/metabolismo , Fosfoproteínas/metabolismo , RNA Mensageiro/metabolismo , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Ácidos Indolacéticos/metabolismo , Proteínas Nucleares , Proteínas de Transporte Nucleocitoplasmático , Transporte Proteico , Proteínas de Ligação a RNA , Transcriptoma , Dedos de Zinco
5.
J Lab Physicians ; 11(2): 154-160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31160856

RESUMO

BACKGROUND: Rapid turnaround time of blood culture reports should be the main motive for a clinical microbiologist for optimal patient care. Categorical agreement (CA) between direct disk diffusion (dDD) and reference disk diffusion (rDD) may vary between laboratories. AIMS AND OBJECTIVES: This study was designed to determine the CA and understand various types of errors associated with antibiotic organism combination, so that caution can be derived while interpreting and reporting dDD results in the earliest meaningful time frame. MATERIALS AND METHODS: In the present study, dDD results were compared to the rDD results from the positive blood culture bottles. CA and various types of errors were evaluated. RESULTS: A total of 965 pathogens and 7106 organism antibiotic combinations were evaluated in this study. Overall, there was a CA of 96% which was extremely satisfactory. The categorical disagreement was found only in 4% of organism antibiotic combinations; majority of which were major error (ME, 2.1%) followed by very ME (1%) and minor error (0.9%). The errors were marginally high for Enterobacteriaceae testing against ß lactam- ß lactamase inhibitor combinations, for Pseudomonas species against aminoglycosides and ciprofloxacin and Staphylococcus species against cefoxitin, one should be vigilant while reporting dDD result of these antibiotic organism combinations. CONCLUSION: dDD is of paramount importance for early institution of targeted therapy and is considered as one of the key stewardship intervention. Our study gives an insight that every laboratory must perform dDD for positively flagged blood culture specimens; the result of which should be confirmed later by performing rDD. One should be vigilant while reporting dDD result of BL BLI for Enterobacteriaceae; aminoglycosides and CF for Pseudomonas species; cefoxitin for Staphylococcus species and HLG for Enterococcus species. Supplementary tests such as MRSA latex should be included when necessary.

6.
Anaerobe ; 57: 82-85, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30951829

RESUMO

Fusobacterium is a gram negative obligate anaerobic bacilli, a normal inhabitant of gastrointestinal tract, oropharynx and female genital tract. Here we report a case of Fourniers gangrene from which Fusobacterium varium has been isolated along with certain other pathogens. There are only a few reported cases of Fusobacterium varium in literature and it has never been reported from Fournier's gangrene. Through this report we intend to shed some light on the pathogenic potential of anaerobes which are considered as normal flora.


Assuntos
Gangrena de Fournier/diagnóstico , Gangrena de Fournier/patologia , Infecções por Fusobacterium/diagnóstico , Infecções por Fusobacterium/patologia , Fusobacterium/isolamento & purificação , Gangrena de Fournier/microbiologia , Fusobacterium/classificação , Infecções por Fusobacterium/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade
7.
BMJ Case Rep ; 12(1)2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30659010

RESUMO

Vibrio vulnificus is a halophilic Vibrio found globally. They are thought to be normal microbiome in the estuaries along the coasts associated with seawater and seashells. Infection usually results from consumption of raw oysters or shellfish or exposure of broken skin or open wounds to contaminated salt or brackish water. Clinical manifestations range from gastroenteritis to skin and subcutaneous infection and primary sepsis. Pathogen has the ability to cause infections with significant mortality in high-risk populations, including patients with chronic liver disease, immunodeficiency, diabetes mellitus and iron storage disorders. There is often a lack of clinical suspicion in cases due to Vibrio vulnificus leading to delay in treatment and subsequent mortality. Herein we report a case of necrotising fasciitis in a diabetic patient with alcoholic liver disease caused by Vibrio vulnificus which ended fatally.


Assuntos
Fasciite Necrosante/microbiologia , Vibrioses/diagnóstico , Vibrio vulnificus/isolamento & purificação , Diabetes Mellitus/microbiologia , Evolução Fatal , Humanos , Hepatopatias Alcoólicas/microbiologia , Masculino , Pessoa de Meia-Idade
8.
Nat Commun ; 9(1): 2407, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921878

RESUMO

Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5' splice site (5'ss). NS1-BP binds most proximal to the 5'ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins.


Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Influenza Humana/genética , Proteínas Nucleares/genética , Precursores de RNA/genética , Splicing de RNA , RNA Mensageiro/genética , Fatores de Transcrição/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Humanos , Vírus da Influenza A/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , Mutação , Proteínas Nucleares/metabolismo , Precursores de RNA/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Proteínas de Ligação a RNA , Ribonucleoproteína Nuclear Pequena U1/genética , Ribonucleoproteína Nuclear Pequena U1/metabolismo , Fatores de Transcrição/metabolismo , Replicação Viral/genética
9.
Contemp Clin Dent ; 9(2): 231-236, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29875566

RESUMO

Context: A major goal in pediatric dentistry is preservation of the integrity of primary teeth and their supporting tissues until physiological process of exfoliation takes place. Pulpectomy serves such a purpose using various materials and techniques to fill the canals of primary teeth. Aims: The aim of this in vivo study was to determine the efficacy of modified disposable syringe technique in root canals of primary molars using digital radiography when obturated with endoflas. Settings and Design: A clinical study was undertaken for a period of 6 months. Subjects and Methods: A total of 60 primary maxillary and mandibular molars were selected in the age group of 4-8 years and randomly divided into two groups. The teeth were obturated with handheld lentulospiral and a modified disposable syringe techniques. Postoperative radiographic evaluation was done for quality of fill and voids using digital radiography. Statistical Analysis Used: Results were assessed using Chi-square test and Mann-Whitney U-test. Results: No statistically significant difference between quality of obturation using hand-held lentulospiral and modified disposable syringe (P < 0.05) was observed. Optimal obturation was achieved in both techniques; however, voids in obturation were not significant. Conclusions: Both the hand-held lentulospiral and modified disposable syringe technique are effective in the obturation of primary molar root canals in terms of quality of fill.

10.
Am J Infect Control ; 46(7): 775-780, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29753498

RESUMO

BACKGROUND: Healthcare-associated infections (HAIs) are a major threat to patient safety worldwide. HAIs are mainly transmitted via the hands of healthcare workers (HCWs), and HCW compliance with hand hygiene (HH) practices is reportedly low. Therefore, multimodal interventions are needed to develop effective HH improvement strategies. In this study, we assessed the effect of multimodal interventions on improvement of HH compliance. METHODS: This study was conducted in 2 intensive care units from August 2016 to October 2016. It encompassed 3 phases: pre-intervention (20 days), intervention (1 month), and post-intervention (20 days). A total of 53 HCWs, including physicians, nurses, and housekeeping staff, were included in the HH audit. The audit was analyzed by direct observation and by a completed knowledge, attitude, and practice (KAP) questionnaire. RESULTS: A total of 6350 HH opportunities were recorded; the results were 34.7%, 35%, and 69.7% for hand hygiene complete adherence rate (HHCAR), hand hygiene partial adherence rate (HHPAR), and hand hygiene adherence rate (HHAR), respectively. The HHCAR in the pre-intervention and post-intervention phases were 3% and 70.1%, respectively. HHCAR was highest among nurses (3.6% in the pre-intervention phase and 80.7% in the post-intervention phase). Other findings were that senior physicians had better HH compliance than junior physicians; in the pre-intervention phase, the HHCAR was better in the evening (4.8%); in the post-intervention phase, the HHCAR was better in the morning (72.1%); women had a higher HHCAR than men; and in the pre-intervention phase, good compliance was seen with Moments 2 and 3 of the World Health Organization's (WHO) Five Moments for Hand Hygiene, whereas in the post-intervention phase, good compliance was seen with Moments 3, 4, and 5. Questionnaire-based data were also analyzed to assess KAP of HH. We found that only 55%-82% of HCWs were aware of the WHO's Five Moments for Hand Hygiene. In the post-intervention phase, we observed a significant improvement in KAP of the study group. CONCLUSION: Significant improvement in HH compliance can be achieved through a systematic, multidimensional intervention involving all types of HCWs.


Assuntos
Infecção Hospitalar/prevenção & controle , Fidelidade a Diretrizes , Higiene das Mãos , Controle de Infecções , Atitude do Pessoal de Saúde , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Unidades de Terapia Intensiva , Masculino , Inquéritos e Questionários , Centros de Atenção Terciária
11.
Am J Infect Control ; 45(5): 498-501, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28131421

RESUMO

BACKGROUND: Hand hygiene (HH) practice is considered the most simple, cost-effective, and efficient way to prevent device-associated infections. Continuous auditing plays a vital role in the conversion of HH knowledge into practice. METHODS: An HH audit was carried out October 2015-September 2016 in 18 locations for a total of 1,080 observation periods and 64,800 minutes of observation. HH complete adherence rate (HHCAR) and HH partial adherence rate were analyzed. RESULTS: The HHCAR, HH partial adherence rate, and nonadherence rate were 45.5%, 21.17%, and 33.3%, respectively. There was gradual statistically significant increase in monthly HHCAR during the study period from 37.5%-51.7% (P = .001). HHCAR was found to be highest among nurses (58.9%) followed by other staff (46.7%) and doctors (46.6%). World Health Organization Moments 3 and 4 had statistically significant compliance (78.5% and 71.8%, respectively; P < .001) compared with Moments 1, 2, and 5. As the HHCAR increases there is statistically significant decrease in device-associated infection rate from 10.6-3.9 per 1,000 device days (P = .042). CONCLUSIONS: HH audit has a significant influence on HH compliance. More emphasis needs to be given on compliance with HH practice by doctors and with the World Health Organization "before" Moments, especially. HH audits should be a part of the infection control manual of every hospital.


Assuntos
Desinfecção/métodos , Desinfecção/estatística & dados numéricos , Fidelidade a Diretrizes , Higiene das Mãos/métodos , Auditoria de Enfermagem/estatística & dados numéricos , Infecção Hospitalar/prevenção & controle , Hospitais de Ensino , Humanos , Índia , Estudos Prospectivos , Setor Público , Centros de Atenção Terciária
14.
Vaccine ; 34(8): 1115-25, 2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26700891

RESUMO

Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15-20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy.


Assuntos
Adenoviridae , Hepacivirus/genética , Hepatite C/prevenção & controle , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas contra Hepatite Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Baculoviridae , Feminino , Genótipo , Células HEK293 , Anticorpos Anti-Hepatite C/sangue , Humanos , Imunidade Celular , Imunidade Humoral , Imunização Secundária , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Linfócitos T/imunologia
15.
J Clin Diagn Res ; 9(6): ZD08-10, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26266225

RESUMO

Oligodontia is congenital absence of one or more teeth which has familial abnormality and attributable to various mutations or polymorphisms of genes often associated with malformative syndromes. The present case reports a rare case of non syndromic oligodontia in an 8-year-old girl with missing 14 permanent teeth excluding third molars in mixed dentition. It is a rare finding which has not been frequently documented in Indian children. Mutations in MSX1 and PAX9 have been described in families in which inherited oligodontia characteristically involves permanent incisors, lateral incisors, premolars and molars. Our study analysed one large family with dominantly inherited oligodontia clinically and genetically. This phonotype is distinct from oligodontia phenotypes associated with mutations in PAX9. Sequencing of the PAX9 revealed a novel mutation in the paired domain of the molecule. The multiple sequence alignment and SNP analysis of the PAX9 exon 2 revealed two mutations.

16.
Plant J ; 84(1): 216-27, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26252423

RESUMO

Barley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole-genome shotgun sequences with a physical and genetic framework. However, because only 6278 bacterial artificial chromosome (BACs) in the physical map were sequenced, fine structure was limited. To gain access to the gene-containing portion of the barley genome at high resolution, we identified and sequenced 15 622 BACs representing the minimal tiling path of 72 052 physical-mapped gene-bearing BACs. This generated ~1.7 Gb of genomic sequence containing an estimated 2/3 of all Morex barley genes. Exploration of these sequenced BACs revealed that although distal ends of chromosomes contain most of the gene-enriched BACs and are characterized by high recombination rates, there are also gene-dense regions with suppressed recombination. We made use of published map-anchored sequence data from Aegilops tauschii to develop a synteny viewer between barley and the ancestor of the wheat D-genome. Except for some notable inversions, there is a high level of collinearity between the two species. The software HarvEST:Barley provides facile access to BAC sequences and their annotations, along with the barley-Ae. tauschii synteny viewer. These BAC sequences constitute a resource to improve the efficiency of marker development, map-based cloning, and comparative genomics in barley and related crops. Additional knowledge about regions of the barley genome that are gene-dense but low recombination is particularly relevant.


Assuntos
Cromossomos Artificiais Bacterianos/genética , Genoma de Planta/genética , Hordeum/genética , Dados de Sequência Molecular
17.
Nucleic Acids Res ; 43(5): 2888-901, 2015 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-25712089

RESUMO

Translation initiation in Hepatitis C Virus (HCV) is mediated by Internal Ribosome Entry Site (IRES), which is independent of cap-structure and uses a limited number of canonical initiation factors. During translation initiation IRES-40S complex formation depends on high affinity interaction of IRES with ribosomal proteins. Earlier, it has been shown that ribosomal protein S5 (RPS5) interacts with HCV IRES. Here, we have extensively characterized the HCV IRES-RPS5 interaction and demonstrated its role in IRES function. Computational modelling and RNA-protein interaction studies demonstrated that the beta hairpin structure within RPS5 is critically required for the binding with domains II and IV. Mutations disrupting IRES-RPS5 interaction drastically reduced the 80S complex formation and the corresponding IRES activity. Computational analysis and UV cross-linking experiments using various IRES-mutants revealed interplay between domains II and IV mediated by RPS5. In addition, present study demonstrated that RPS5 interaction is unique to HCV IRES and is not involved in 40S-3' UTR interaction. Further, partial silencing of RPS5 resulted in preferential inhibition of HCV RNA translation. However, global translation was marginally affected by partial silencing of RPS5. Taken together, results provide novel molecular insights into IRES-RPS5 interaction and unravel its functional significance in mediating internal initiation of translation.


Assuntos
Hepacivirus/metabolismo , RNA Viral/metabolismo , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo , Sítios de Ligação/genética , Western Blotting , Linhagem Celular Tumoral , Hepacivirus/química , Hepacivirus/genética , Humanos , Modelos Moleculares , Mutação , Conformação de Ácido Nucleico , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Interferência de RNA , RNA Viral/química , RNA Viral/genética , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genética
18.
RNA Biol ; 11(7): 891-905, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25268799

RESUMO

In this study, we combine available high resolution structural information on eukaryotic ribosomes with low resolution cryo-EM data on the Hepatitis C Viral RNA (IRES) human ribosome complex. Aided further by the prediction of RNA-protein interactions and restrained docking studies, we gain insights on their interaction at the residue level. We identified the components involved at the major and minor contact regions, and propose that there are energetically favorable local interactions between 40S ribosomal proteins and IRES domains. Domain II of the IRES interacts with ribosomal proteins S5 and S25 while the pseudoknot and the downstream domain IV region bind to ribosomal proteins S26, S28 and S5. We also provide support using UV cross-linking studies to validate our proposition of interaction between the S5 and IRES domains II and IV. We found that domain IIIe makes contact with the ribosomal protein S3a (S1e). Our model also suggests that the ribosomal protein S27 interacts with domain IIIc while S7 has a weak contact with a single base RNA bulge between junction IIIabc and IIId. The interacting residues are highly conserved among mammalian homologs while IRES RNA bases involved in contact do not show strict conservation. IRES RNA binding sites for S25 and S3a show the best conservation among related viral IRESs. The new contacts identified between ribosomal proteins and RNA are consistent with previous independent studies on RNA-binding properties of ribosomal proteins reported in literature, though information at the residue level is not available in previous studies.


Assuntos
Microscopia Crioeletrônica/métodos , Hepacivirus/genética , RNA Viral/química , Subunidades Ribossômicas Maiores/química , Sequência de Bases , Sítios de Ligação , Sequência Conservada , Hepacivirus/química , Humanos , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Estrutura Secundária de Proteína , RNA Viral/metabolismo , Subunidades Ribossômicas Maiores/metabolismo
19.
J Clin Diagn Res ; 8(8): ZD43-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25302284

RESUMO

Preservation of the primary dentition until the normal time of exfoliation is one of the most important factor involved in preventive and interceptive dentistry. The premature loss of second primary molar before the eruption of permanent first molar can create a significant arch space/tooth size discrepancy. Distal shoe space maintainer is a valuable part of the Paediatric Dentist's armamentarium in those cases where the second primary molar is prematurely lost and it helps to guide the first permanent molar into place. Conventional design poses various limitations in cases of premature loss of multiple deciduous molars. Thus, it is required to modify the conventional designs according to the needs of the patient. This case report describes an innovative modification of distal shoe appliance in cases of premature loss of multiple deciduous molars. In the present case, modification of distal shoe space maintainer was advocated because of inadequate abutments caused due to multiple loss of deciduous molars. Bilateral design of distal shoe was planned for unilateral loss of deciduous molars.

20.
Trends Microbiol ; 22(2): 57-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24387882

RESUMO

In a recent Nature paper, Hashem et al. attempted to probe deeper into the elusive role of eIF3 in translation initiation of viruses with hepatitis C virus-like internal ribosome entry sites (IRESs), but instead uncovered a surprising role of these IRESs in displacing eIF3 from the 40S subunit, favoring viral translation.


Assuntos
Vírus da Febre Suína Clássica/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , Sequências Reguladoras de Ácido Ribonucleico/genética , Subunidades Ribossômicas Menores de Eucariotos/metabolismo , Ribossomos/metabolismo , Animais , Humanos
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