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1.
Sensors (Basel) ; 21(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34450901

RESUMO

The introduction of 5G with excessively high speeds and ever-advancing cellular device capabilities has increased the demand for high data rate wireless multimedia communication. Data compression, transmission robustness and error resilience are introduced to meet the increased demands of high data rates of today. An innovative approach is to come up with a unique setup of source bit codes (SBCs) that ensure the convergence and joint source-channel coding (JSCC) correspondingly results in lower bit error ratio (BER). The soft-bit assisted source and channel codes are optimized jointly for optimum convergence. Source bit codes assisted by iterative detection are used with a rate-1 precoder for performance evaluation of the above mentioned scheme of transmitting sata-partitioned (DP) H.264/AVC frames from source through a narrowband correlated Rayleigh fading channel. A novel approach of using sphere packing (SP) modulation aided differential space time spreading (DSTS) in combination with SBC is designed for the video transmission to cope with channel fading. Furthermore, the effects of SBC with different hamming distances d(H,min) but similar coding rates is explored on objective video quality such as peak signal to noise ratio (PSNR) and also the overall bit error ratio (BER). EXtrinsic Information Transfer Charts (EXIT) are used for analysis of the convergence behavior of SBC and its iterative scheme. Specifically, the experiments exhibit that the proposed scheme of error protection of SBC d(H,min) = 6 outperforms the SBCs having same code rate, but with d(H,min) = 3 by 3 dB with PSNR degradation of 1 dB. Furthermore, simulation results show that a gain of 27 dB Eb/N0 is achieved with SBC having code rate 1/3 compared to the benchmark Rate-1 SBC codes.

2.
BMJ Open ; 14(1): e081188, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38296304

RESUMO

OBJECTIVE: Living Library events involve people being trained as living 'Books', who then discuss aspects of their personal experiences in direct conversation with attendees, referred to as 'Readers'. This study sought to generate a realist programme theory and a theory-informed implementation guide for a Library of Lived Experience for Mental Health (LoLEM). DESIGN: Integrated realist synthesis and experience-based co-design. SETTING: Ten online workshops with participants based in the North of England. PARTICIPANTS: Thirty-one participants with a combination of personal experience of using mental health services, caring for someone with mental health difficulties and/or working in mental health support roles. RESULTS: Database searches identified 30 published and grey literature evidence sources which were integrated with data from 10 online co-design workshops conducted over 12 months. The analysis generated a programme theory comprising five context-mechanism-outcome (CMO) configurations. Findings highlight how establishing psychological safety is foundational to productive Living Library events (CMO 1). For Readers, direct conversations humanise others' experiences (CMO 2) and provide the opportunity to flexibly explore new ways of living (CMO 3). Through participation in a Living Library, Books may experience personal empowerment (CMO 4), while the process of self-authoring and co-editing their story (CMO 5) can contribute to personal development. This programme theory informed the co-design of an implementation guide highlighting the importance of tailoring event design and participant support to the contexts in which LoLEM events are held. CONCLUSIONS: The LoLEM has appeal across stakeholder groups and can be applied flexibly in a range of mental health-related settings. Implementation and evaluation are required to better understand the positive and negative impacts on Books and Readers. TRIAL REGISTRATION NUMBER: PROSPERO CRD42022312789.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Empoderamento , Inglaterra , Pesquisa Qualitativa
3.
Cureus ; 15(5): e39007, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37378254

RESUMO

Neurofibromatosis type 1 (NF1) or von Recklinghausen syndrome is an autosomal dominant disorder that affects the multisystem in the body with complex presentation caused by the neurofibromin gene mutation on chromosome 17. These patients tend to develop soft tissue sarcomas more than the general population. Leiomyosarcoma is a malignant soft tissue tumor that may occur in patients with NF1 in rare cases. We present a case of a rare development of leiomyosarcoma in a 45-year-old female patient with a history of NF1. She developed a progressively growing mass in the left axilla associated with numerous neurofibromas and axillary freckling. MRI revealed a heterogeneous large mixed signal intensity mass in the left axilla, and the diagnosis was confirmed through biopsy.

4.
BMJ Open ; 13(3): e068548, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36889824

RESUMO

INTRODUCTION: People with lived expertise in managing mental health challenges can be an important source of knowledge and support for other people facing similar challenges, and for carers to learn how best to help. However, opportunities for sharing lived expertise are limited. Living libraries support people with lived expertise to be 'living books', sharing their experiences in dialogue with 'readers' who can ask questions. Living libraries have been piloted worldwide in health-related contexts but without a clear model of how they work or rigorous evaluation of their impacts. We aim to develop a programme theory about how a living library could be used to improve mental health outcomes, using this theory to codesign an implementation guide that can be evaluated across different contexts. METHODS AND ANALYSIS: We will use a novel integration of realist synthesis and experience-based codesign (EBCD) to produce a programme theory about how living libraries work and a theory and experience informed guide to establishing a library of lived experience for mental health (LoLEM). Two workstreams will run concurrently: (1) a realist synthesis of literature on living libraries, combined with stakeholder interviews, will produce several programme theories; theories will be developed collaboratively with an expert advisory group of stakeholders who have hosted or taken part in a living library and will form our initial analysis framework; a systematic search will identify literature about living libraries; data will be coded into our analysis framework, and we will use retroductive reasoning to explain living libraries' impacts across multiple contexts. Individual stakeholder interviews will help refine and test theories; (2) data from workstream 1 will inform 10 EBCD workshops with people with experience of managing mental health difficulties and health professionals to produce a LoLEM implementation guide; data from this process will also inform the theory in workstream 1. ETHICS AND DISSEMINATION: Ethical approval was granted by Coventry and Warwick National Health Service Research Ethics Committee on 29 December 2021 (reference number 305975). The programme theory and implementation guide will be published as open access and shared widely through a knowledge exchange event, a study website, mental health provider and peer support networks, peer reviewed journals and a funders report. PROSPERO REGISTRATION DETAILS: CRD42022312789.


Assuntos
Saúde Mental , Medicina Estatal , Humanos , Resolução de Problemas , Aprendizagem
5.
J Med Genet ; 48(1): 48-54, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20972252

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is characterised by impairments in social communication and by a pattern of repetitive behaviours, with learning disability (LD) typically seen in up to 70% of cases. A recent study using the PPL statistical framework identified a novel region of genetic linkage on chromosome 16q21 that is limited to ASD families with LD. METHODS: In this study, two families with autism and/or LD are described which harbour rare >1.6 Mb microdeletions located within this linkage region. The deletion breakpoints are mapped at base-pair resolution and segregation analysis is performed using a combination of 1M single nucleotide polymorphism (SNP) technology, array comparative genomic hybridisation (CGH), long-range PCR, and Sanger sequencing. The frequency of similar genomic variants in control subjects is determined through analysis of published SNP array data. Expression of CDH8, the only gene disrupted by these microdeletions, is assessed using reverse transcriptase PCR and in situ hybridisation analysis of 9 week human embryos. RESULTS: The deletion of chr16: 60 025 584-61 667 839 was transmitted to three of three boys with autism and LD and none of four unaffected siblings, from their unaffected mother. In a second family, an overlapping deletion of chr16: 58 724 527-60 547 472 was transmitted to an individual with severe LD from his father with moderate LD. No copy number variations (CNVs) disrupting CDH8 were observed in 5023 controls. Expression analysis indicates that the two CDH8 isoforms are present in the developing human cortex. CONCLUSION: Rare familial 16q21 microdeletions and expression analysis implicate CDH8 in susceptibility to autism and LD.


Assuntos
Transtorno Autístico/genética , Caderinas/genética , Deleção Cromossômica , Cromossomos Humanos Par 16/genética , Ligação Genética , Predisposição Genética para Doença , Deficiências da Aprendizagem/genética , Adolescente , Sequência de Bases , Caderinas/metabolismo , Criança , Variações do Número de Cópias de DNA/genética , Análise Mutacional de DNA , Família , Feminino , Regulação da Expressão Gênica , Genoma Humano/genética , Humanos , Testes de Inteligência , Internet , Masculino , Dados de Sequência Molecular , Linhagem , Adulto Jovem
6.
Environ Monit Assess ; 184(8): 4623-34, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21892615

RESUMO

Studies on naturally occurring radioactive material (NORM) in the limestone from the Margalla Hills have been carried out by measuring gamma activity and to access its radiological implications if any. For data acquisition, a High-Purity Germanium detector was employed. The activity concentrations of (226)Ra, (232)Th, and (40)K were found to be 14.32 ± 0.24, 2.05 ± 0.04, and 13.80 ± 0.20 Bq kg(-1), respectively. These values are relatively lower as compared to that in the limestone of other countries and much lower than the values reported for the natural building stones. The average specific activities due to (226)Ra were found to be higher when compared with (40)K and (232)Th. Indices of radium equivalent activity (Ra(eq)), internal hazard (H(in)), indoor absorbed gamma dose rate (D(R,)), and corresponding annual effective dose (E(eff)) were also determined for the limestone-made rooms. All of these indices were found to be in the lower ranges. The Margalla Hills limestone does not pose any excessive radiological health hazard as a building material and in industrial uses for a common man.


Assuntos
Monitoramento de Radiação , Poluentes Radioativos do Solo/análise , Carbonato de Cálcio/química , Materiais de Construção/análise , Materiais de Construção/estatística & dados numéricos , Paquistão , Medição de Risco
7.
3 Biotech ; 11(2): 50, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33457174

RESUMO

The novel coronavirus infection (COVID-19) is not diminishing without vaccine, but it impinges on human safety and economy can be minimized by adopting smart technology to combat pandemic situation. The implementation of new innovations and novel tactics has proven to be effective in curbing the risk of COVID-19. The present study covers the role of smart technology in mitigating the spread of COVID-19 with specific focus on advancement in the field of drone, robotics, artificial intelligence (AI), mask, and sensor technology. The findings shed light on the robotics and drone technology-driven approaches that have been applied for assisting health system, surveillance, and disinfection process, etc. The AI technology strategies and framework is highlighted in terms of bulk data computing, predicting infection threats, providing medical assistance, and analyzing diagnosis results. Besides this, the technological shift in mask and sensor technology during the pandemic have been illustrated, which includes fabrication method like 3D printing and optical sensing, respectively. Furthermore, the strength, weakness, opportunities, and possible threats that have been shaped by the rigorous implementation of these technologies are also covered in detail.

8.
Nucleic Acids Res ; 36(9): 3043-53, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18397952

RESUMO

Cryptophytes are unicellular eukaryotic algae that acquired photosynthesis secondarily through the uptake and retention of a red-algal endosymbiont. The plastid genome of the cryptophyte Rhodomonas salina CCMP1319 was recently sequenced and found to contain a genetic element similar to a group II intron. Here, we explore the distribution, structure and function of group II introns in the plastid genomes of distantly and closely related cryptophytes. The predicted secondary structures of six introns contained in three different genes were examined and found to be generally similar to group II introns but unusually large in size (including the largest known noncoding intron). Phylogenetic analysis suggests that the cryptophyte group II introns were acquired via lateral gene transfer (LGT) from a euglenid-like species. Unexpectedly, the six introns occupy five distinct genomic locations, suggesting multiple LGT events or recent transposition (or both). Combined with structural considerations, RT-PCR experiments suggest that the transferred introns are degenerate 'twintrons' (i.e. nested group II/group III introns) in which the internal intron has lost its splicing capability, resulting in an amalgamation with the outer intron.


Assuntos
Criptófitas/genética , Transferência Genética Horizontal , Genomas de Plastídeos , Íntrons , Proteínas de Algas/classificação , Proteínas de Algas/genética , Sequência de Bases , Variação Genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Filogenia , Splicing de RNA
9.
J Ayub Med Coll Abbottabad ; 22(2): 180-3, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21702298

RESUMO

BACKGROUND: Cervical radiculopathy is a common and distressing problem. Only those patients who failed conservative treatment should undergo surgery. The anterior cervical disectomy is the procedure which offers maximal exposure of the disc space. It easily removes the portion of disc which compresses the nerve root. Possibility of developing late kyphosis from disc space collapse supported the fusion procedure after single level disectomy. The goal of instrumentation is to provide immediate stability, increase fusion rate, prevent graft failure, improve rehabilitation process and possibly no need for external orthosis. Objective of study was To see the results and complications of cervical disectomy thru anterior approach and fusion and stabilisation with titanium made plate. METHODS: This was a prospective study, comprised of 32 patients admitted during period from 2005-2008. Patients presented with radiculopathy or radiculo-myelopathy were evaluated. MRI was carried out in all the cases. Each patient was carefully evaluated to confirm clinico-radiological correlation and patients with significant disc and failure of conservative treatment were included in the study. RESULTS: Males were 28 (87.5%) and female were 4 (12.5%). Twenty patients (62.5%) were in fourth decade. C5-6 was involved in 18 (56.25%) patients. No significant postoperative complications noted. Persistent neck and back pain noted in patients in disectomy group without plating. CONCLUSION: Anterior cervical disectomy, fusion and stabilisation with plating is a safe and easy procedure in single level cervical disc disease without significant complications.


Assuntos
Vértebras Cervicais , Discotomia , Fixadores Internos , Radiculopatia/cirurgia , Fusão Vertebral , Adulto , Idoso , Placas Ósseas , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiculopatia/etiologia , Radiculopatia/patologia , Resultado do Tratamento , Adulto Jovem
10.
Ann Saudi Med ; 36(4): 258-64, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27478911

RESUMO

BACKGROUND: Patient attendance in the emergency department (ED) is inherently variable and unpredictable. Resources might be better allocated if use of the ER could be predicted during the month of fasting (Ramadan), healthy adult Muslims do not eat or drink from dawn to sunset and in the Middle East, social activities occur mostly during night. There is no published data that has reported changes in local ED attendance pattern during Ramadan. OBJECTIVES: Determine if there are differences in tertiary care ed attendance during Ramadan compared to other times of the year. DESIGN: Retrospective, using data from the hospital integrated clinical information system. SETTING: Tertiary care institution in Riyadh, Saudi Arabia. PATIENTS AND METHODS: All ED visits during the Islamic calendar years of 1431-1434 (December 18, 2009-October 13, 2013) were analyzed. MAIN OUTCOME MEASURES: Patient volume, acuity, demographics and admission rate variability between Ramadan and other months. RESULTS: During the study period of 4 years, of 226075 ED patients, 129178 (57.14%) patients were seen during the day shift (07:00 to 18:59). During Ramadan, 10 293 (60%) patients presented during the night shift compared with the day shift (P < .0001). This trend was seen consistently with no statistically significant differences in admissions 7%, triage acuity or when compared with other months. CONCLUSION: During Ramadan, ED attendance changes as more patients present during the night shift. In Saudi Arabia and possibly other Muslim countries, appropriate resources should be allocated during Ramadan to manage the nocturnal ED patient surge. LIMITATIONS: We believe that the majority of our patients fast, but it is not known how many ED patients were actually fasting during the study period. This study was conducted in a tertiary care hospital and the patient population presenting to our ed is predominantly Muslim; therefore, the results may not be generalized to populations that are not predominantly Muslim.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Islamismo , Centros de Atenção Terciária , Adolescente , Adulto , Serviço Hospitalar de Emergência/tendências , Feminino , Humanos , Masculino , Gravidade do Paciente , Admissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Arábia Saudita , Fatores de Tempo , Adulto Jovem
11.
Radiat Prot Dosimetry ; 157(1): 73-84, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23630384

RESUMO

The Lawrencepur sand had remained refrigerated during a long period of glaciations in the study area. Owing to its derivation from the granitic rocks of the Himalayas and its preservation under glacial environment, the sand grains are still fresh and may contain high level of primordial radioactivity. For that reason, radiological hazards of Lawrencepur sand were assessed using a high-purity germanium gamma spectrometry technique. The average activity concentrations of (226)Ra, (232)Th and (40)K were found to be 15.97±3.05, 27.98±4.89 and 498.20±15.91 Bq kg(-1), respectively. These values are higher than those of the sands of many countries of the world but lower than those of some of the Pakistani, Indian and Egyptian sands. The outdoor and indoor hazard indices and annual effective doses of the Lawrencepur sand are higher than those of some of the sand deposits of European, African and American countries but lower than those of nearby Pakistani and Indian sands. However, the hazard indices and annual effective doses of the Lawrencepur sand are within the safe limits. Overall, the Lawrencepur sand does not pose any radiological health hazard as a building material.


Assuntos
Monitoramento de Radiação , Dióxido de Silício/química , Poluentes Radioativos do Solo/análise , Raios gama , Germânio , Humanos , Paquistão , Radioisótopos de Potássio/análise , Doses de Radiação , Rádio (Elemento)/análise , Dióxido de Silício/análise , Tório/análise
12.
PLoS One ; 7(10): e38167, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23077474

RESUMO

Bacteria, plants, and algae produce isoprenoids through the methylerythritol phosphate (MEP) pathway, an attractive pathway for antimicrobial drug development as it is present in prokaryotes and some lower eukaryotes but absent from human cells. The first committed step of the MEP pathway is catalyzed by 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR/MEP synthase). MEP pathway genes have been identified in many biothreat agents, including Francisella, Brucella, Bacillus, Burkholderia, and Yersinia. The importance of the MEP pathway to Francisella is demonstrated by the fact that MEP pathway mutations are lethal. We have previously established that fosmidomycin inhibits purified MEP synthase (DXR) from F. tularensis LVS. FR900098, the acetyl derivative of fosmidomycin, was found to inhibit the activity of purified DXR from F. tularensis LVS (IC(50)=230 nM). Fosmidomycin and FR900098 are effective against purified DXR from Mycobacterium tuberculosis as well, but have no effect on whole cells because the compounds are too polar to penetrate the thick cell wall. Fosmidomycin requires the GlpT transporter to enter cells, and this is absent in some pathogens, including M. tuberculosis. In this study, we have identified the GlpT homologs in F. novicida and tested transposon insertion mutants of glpT. We showed that FR900098 also requires GlpT for full activity against F. novicida. Thus, we synthesized several FR900098 prodrugs that have lipophilic groups to facilitate their passage through the bacterial cell wall and bypass the requirement for the GlpT transporter. One compound, that we termed "compound 1," was found to have GlpT-independent antimicrobial activity. We tested the ability of this best performing prodrug to inhibit F. novicida intracellular infection of eukaryotic cell lines and the caterpillar Galleria mellonella as an in vivo infection model. As a lipophilic GlpT-independent DXR inhibitor, compound 1 has the potential to be a broad-spectrum antibiotic, and should be effective against most MEP-dependent organisms.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Fosfomicina/análogos & derivados , Francisella/efeitos dos fármacos , Pró-Fármacos/farmacologia , Animais , Catálise , Linhagem Celular , Fosfomicina/farmacologia , Humanos , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Microbiana
13.
J Radiat Res ; 53(3): 411-21, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22739011

RESUMO

The Khewra Salt Mines, the second largest salt mines in the world, are located 160 km south of Islamabad, the capital of Pakistan. Around 1000 workers are involved in the removal of salt from these mines. More than 40,000 visitors come annually to see the mines. The visitors and workers are directly exposed to the internal and external radiological hazards of radon and gamma rays in these mines. The general public is affected by the intake of the salt containing the naturally occurring radionuclides. Therefore the concentration of radon (²²²Rn) in the Khewra Salt Mines and activity concentrations of the naturally occurring radionuclides in the salt samples from these mines were measured. Both active and passive techniques were employed for the measurement of radon with Radon Alpha Detector (RAD-7) and SSNTD respectively. The concentration of ²²²Rn was 26 ± 4 Bq m⁻³ measured by the active method while 43 ± 8 Bq m⁻³ was measured by the passive method. The activity concentration of the radionuclides was measured using gamma ray spectrometry with HPGe detector. The mean activity of 4°K in salt samples was found to be 36 ± 20 Bq kg⁻¹ and the concentration of ²²6Ra and ²³²Th in the salt samples was below the detection limits. Gamma radiation hazard was assessed in terms of the external gamma dose from salt slabs and the rooms made of salt and the annual effective dose due to gamma radiation. The exposure to radon daughters, annual effective dose and excessive lifetime cancer risk due to radon in the mines were estimated. The mean annual effective dose due to an intake of 4°K from the salt was calculated as 20.0 ± 11.1 µSv, which is lower than the average annual effective dose rate of 0.29 mSv, received by the ingestion of natural radionuclides. Due to the low concentration values of primordial radionuclides in the salt and radon ²²²Rn) in the mines, a 'low level activity measurement laboratory' is suggested to be established in these mines.


Assuntos
Radiação de Fundo/efeitos adversos , Mineração , Raios gama/efeitos adversos , Substâncias Perigosas/efeitos adversos , Humanos , Paquistão , Radioisótopos/isolamento & purificação , Radiometria/instrumentação , Radônio/efeitos adversos , Cloreto de Sódio/isolamento & purificação
14.
Gen Hosp Psychiatry ; 34(6): 618-25, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22459999

RESUMO

BACKGROUND: This research examines the physical health of patients with severe, chronic obsessive-compulsive disorder (OCD) and compares the findings with patients admitted to an acute general psychiatric ward. METHODS: Successive admissions to a specialist inpatient unit treating patients with OCD were included in the study. Information including gender, age, weight and height were recorded along with the results of blood tests for urea, liver function tests and blood lipids. In addition, type and dose of medication were also recorded. These data were compared with information obtained via the case records from successive admissions to a general psychiatric ward. RESULTS: A total of 104 patients with OCD and 101 patients admitted to an acute psychiatric unit were studied. OCD patients were generally younger than the controls and were on a lower dose of antipsychotic medication. Despite this, the OCD patients were more likely than the general psychiatric patients to have raised blood lipids. Raised creatinine was also more common among OCD patients. CONCLUSION: The study demonstrates that patients with severe OCD have significant evidence of serious physical health problems.


Assuntos
Hiperlipidemias/epidemiologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Insuficiência Renal/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Incontinência Urinária/epidemiologia
15.
J Neurodev Disord ; 3(2): 113-23, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21484201

RESUMO

The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well.

16.
J Mol Evol ; 64(2): 223-36, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17211547

RESUMO

The cryptomonads are an enigmatic group of unicellular eukaryotic algae that possess two nuclear genomes, having acquired photosynthesis by the uptake and retention of a eukaryotic algal endosymbiont. The endosymbiont nuclear genome, or nucleomorph, of the cryptomonad Guillardia theta has been completely sequenced: at only 551 kilobases (kb) and with a gene density of approximately 1 gene/kb, it is a model of compaction. In contrast, very little is known about the structure and composition of the cryptomonad host nuclear genome. Here we present the results of two small-scale sequencing surveys of fosmid clone libraries from two distantly related cryptomonads, Rhodomonas salina CCMP1319 and Cryptomonas paramecium CCAP977/2A, corresponding to approximately 150 and approximately 235 kb of sequence, respectively. Very few of the random end sequences determined in this study show similarity to known genes in other eukaryotes, underscoring the considerable evolutionary distance between the cryptomonads and other eukaryotes whose nuclear genomes have been completely sequenced. Using a combination of fosmid clone end-sequencing, Southern hybridizations, and PCR, we demonstrate that Ty3-gypsy long-terminal repeat (LTR) retrotransposons and tandem repeat sequences are a prominent feature of the nuclear genomes of both organisms. The complete sequence of a 30.9-kb genomic fragment from R. salina was found to contain a full-length Ty3-gypsy element with near-identical LTRs and a chromodomain, a protein module suggested to mediate the site-specific integration of the retrotransposon. The discovery of chromodomain-containing retroelements in cryptomonads further expands the known distribution of the so-called chromoviruses across the tree of eukaryotes.


Assuntos
Criptófitas/classificação , Criptófitas/genética , Sequências Repetitivas de Ácido Nucleico , Retroelementos , Clonagem Molecular , DNA/genética , DNA/isolamento & purificação , Variação Genética , Filogenia , Reação em Cadeia da Polimerase , Sequências Repetidas Terminais/genética
17.
Mol Biol Evol ; 24(8): 1832-42, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17522086

RESUMO

Cryptophytes are a group of unicellular algae with chlorophyll c-containing plastids derived from the uptake of a secondary (i.e., eukaryotic) endosymbiont. Biochemical and molecular data indicate that cryptophyte plastids are derived from red algae, yet the question of whether or not cryptophytes acquired their red algal plastids independent of those in heterokont, haptophyte, and dinoflagellate algae is of long-standing debate. To better understand the origin and evolution of the cryptophyte plastid, we have sequenced the plastid genome of Rhodomonas salina CCMP1319: at 135,854 bp, it is the largest secondary plastid genome characterized thus far. It also possesses interesting features not seen in the distantly related cryptophyte Guillardia theta or in other red secondary plastids, including pseudogenes, introns, and a bacterial-derived gene for the tau/gamma subunit of DNA polymerase III (dnaX), the first time putative DNA replication machinery has been found encoded in any plastid genome. Phylogenetic analyses indicate that dnaX was acquired by lateral gene transfer (LGT) in an ancestor of Rhodomonas, most likely from a firmicute bacterium. A phylogenomic survey revealed no additional cases of LGT, beyond a noncyanobacterial type rpl36 gene similar to that recently characterized in other cryptophytes and haptophytes. Rigorous concatenated analysis of 45 proteins encoded in 15 complete plastid genomes produced trees in which the heterokont, haptophyte, and cryptophyte (i.e., chromist) plastids were monophyletic, and heterokonts and haptophytes were each other's closest relatives. However, statistical support for chromist monophyly disappears when amino acids are recoded according to their chemical properties in order to minimize the impact of composition bias, and a significant fraction of the concatenate appears consistent with a sister-group relationship between cryptophyte and haptophyte plastids.


Assuntos
Bactérias/genética , Criptófitas/genética , Replicação do DNA , Transferência Genética Horizontal , Genoma , Plastídeos/genética , Evolução Molecular , Genes de Plantas , Filogenia , Análise de Sequência de DNA , Simbiose
18.
Genome Res ; 16(1): 78-87, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16344559

RESUMO

We investigated the evolution of the families of LINE-1 (L1) retrotransposons that have amplified in the human lineage since the origin of primates. We identified two phases in the evolution of L1. From approximately 70 million years ago (Mya) until approximately 40 Mya, three distinct L1 lineages were simultaneously active in the genome of ancestral primates. In contrast, during the last 40 million years (Myr), i.e., during the evolution of anthropoid primates, a single lineage of families has evolved and amplified. We found that novel (i.e., unrelated) regulatory regions (5'UTR) have been frequently recruited during the evolution of L1, whereas the two open-reading frames (ORF1 and ORF2) have remained relatively conserved. We found that L1 families coexisted and formed independently evolving L1 lineages only when they had different 5'UTRs. We propose that L1 families with different 5'UTR can coexist because they don't rely on the same host-encoded factors for their transcription and therefore do not compete with each other. The most prolific L1 families (families L1PA8 to L1PA3) amplified between 40 and 12 Mya. This period of high activity corresponds to an episode of adaptive evolution in a segment of ORF1. The correlation between the high activity of L1 families and adaptive evolution could result from the coevolution of L1 and a host-encoded repressor of L1 activity.


Assuntos
Regiões 5' não Traduzidas/genética , Evolução Molecular , Elementos Nucleotídeos Longos e Dispersos/genética , Fases de Leitura Aberta/genética , Animais , Humanos , Primatas
19.
Mol Biol Evol ; 23(5): 856-65, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16306383

RESUMO

The cryptomonads are an enigmatic group of marine and freshwater unicellular algae that acquired their plastids through the engulfment and retention of a eukaryotic ("secondary") endosymbiont. Together with the chlorarachniophyte algae, the cryptomonads are unusual in that they have retained the nucleus of their endosymbiont in a miniaturized form called a nucleomorph. The nucleomorph genome of the cryptomonad Guillardia theta has been completely sequenced and with only three chromosomes and a total size of 551 kb, is a model of nuclear genome compaction. Using this genome as a reference, we have investigated the structure and content of nucleomorph genomes in a wide range of cryptomonad algae. In this study, we have sequenced nine new cryptomonad nucleomorph 18S ribosomal DNA (rDNA) genes and four heat shock protein 90 (hsp90) gene fragments, and using pulsed-field gel electrophoresis and Southern hybridizations, have obtained nucleomorph genome size estimates for nine different species. We also used long-range polymerase chain reaction to obtain nucleomorph genomic fragments from Hanusia phi CCMP325 and Proteomonas sulcata CCMP704 that are syntenic with the subtelomeric region of nucleomorph chromosome I in G. theta. Our results indicate that (1) the presence of three chromosomes is a common feature of the nucleomorph genomes of these organisms, (2) nucleomorph genome size varies dramatically in the cryptomonads examined, (3) unidentified cryptomonad species CCMP1178 has the largest nucleomorph genome identified to date at approximately 845 kb, (4) nucleomorph genome size reductions appear to have occurred multiple times independently during cryptomonad evolution, (5) the relative positions of the 18S rDNA, ubc4, and hsp90 genes are conserved in three different cryptomonad genera, and (6) interchromosomal recombination appears to be rapidly changing the size and sequence of a repetitive subtelomeric region of the nucleomorph genome between the 18S rDNA and ubc4 loci. These results provide a glimpse into the genetic diversity of nucleomorph genomes in cryptomonads and set the stage for more comprehensive sequence-based studies in closely and distantly related taxa.


Assuntos
Criptófitas/genética , Eucariotos/genética , Genoma , Teorema de Bayes , Evolução Biológica , Southern Blotting , Clonagem Molecular , Sequência Conservada , DNA Ribossômico/genética , Evolução Molecular , Variação Genética , Proteínas de Choque Térmico HSP90/genética , Filogenia , Reação em Cadeia da Polimerase
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