Integrated whole transcriptome and DNA methylation analysis identifies gene networks specific to late-onset Alzheimer’s disease

Previous transcriptome studies observed disrupted cellular processes in late-onset Alzheimer\u27s disease (LOAD), yet it is unclear whether these changes are specific to LOAD, or are common to general neurodegeneration. In this study, we address this question by examining transcription in LOAD and comparing it to cognitively normal controls and a cohort of disease controls. Differential transcription was examined using RNA-seq, which allows for the examination of protein coding genes, non-coding RNAs, and splicing. Significant transcription differences specific to LOAD were observed in five genes: C10orf105, DIO2, a lincRNA, RARRES3, and WIF1. These findings were replicated in two independent publicly available microarray data sets. Network analyses, performed on 2,504 genes with moderate transcription differences in LOAD, reveal that these genes aggregate into seven networks. Two networks involved in myelination and innate immune response specifically correlated to LOAD. FRMD4B and ST18, hub genes within the myelination network, were previously implicated in LOAD. Of the five significant genes, WIF1 and RARRES3 are directly implicated in the myelination process; the other three genes are located within the network. LOAD specific changes in DNA methylation were located throughout the genome and substantial changes in methylation were identified within the myelination network. Splicing differences specific to LOAD were observed across the genome and were decreased in all seven networks. DNA methylation had reduced influence on transcription within LOAD in the myelination network when compared to both controls. These results hint at the molecular underpinnings of LOAD and indicate several key processes, genes, and networks specific to the disease

Математическое и программное обеспечение классификации классов лесов по данным дистанционного зондирования Земли

Цель работы - создание математического и программного обеспечения для отнесения того или иного лесного сообщества конкретного региона России к одному из классов типов лесов. В процессе исследования проводился анализ предметной области и методы решения поставленной задачи, также рассматривались существующие на сегодняшний день аналоги распознавания классов растительного покрова со спутниковых изображений. Область применения: классификация типов лесов на спутниковых снимках и картах, проведение анализа текущего состояния лесных ресурсов, оценка влияния различных внешних факторов на лесные территории. Практическая значимость работы заключается в том, что в ней применена нечеткая модель, основанная на кластеризации, для решения поставленных в работе задач.The aim of this work is to create a software which can determine a class of the forest type of a particular forest community of one of the regions of Russia. In the process of the research a subject area and methods of problem solutions have been analyzed, also currently existing analogs of vegetation cover classes recognition from satellite images have been considered. Scope: a classification of forest types on satellite images and maps, an analysis of the current state of forest resources, an assessment of the influence of various external factors on forest areas. The practical significance of the work is about the fact that a fuzzy model based on clustering has been used to solve the tasks of the project

Perspectives on key principles of generalist medical practice in public service in sub-saharan africa: a qualitative study

The original publication is available at http://www.biomedcentral.comAbstract Background: The principles and practice of Family Medicine that arose in developed Western countries have been imported and adopted in African countries without adequate consideration of their relevance and appropriateness to the African context. In this study we attempted to elicit a priori principles of generalist medical practice from the experience of long-serving medical officers in a variety of African counties, through which we explored emergent principles of Family Medicine in our own context. Methods A descriptive study design was utilized, using qualitative methods. 16 respondents who were clinically active medical practitioners, working as generalists in the public services or non-profit sector for at least 5 years, and who had had no previous formal training or involvement in academic Family Medicine, were purposively selected in 8 different countries in southern, western and east Africa, and interviewed. Results The respondents highlighted a number of key issues with respect to the external environment within which they work, their collective roles, activities and behaviours, as well as the personal values and beliefs that motivate their behaviour. The context is characterized by resource constraints, high workload, traditional health beliefs, and the difficulty of referring patients to the next level of care. Generalist clinicians in sub-Saharan Africa need to be competent across a wide range of clinical disciplines and procedural skills at the level of the district hospital and clinic, in both chronic and emergency care. They need to understand the patient's perspective and context, empowering the patient and building an effective doctor-patient relationship. They are also managers, focused on coordinating and improving the quality of clinical care through teamwork, training and mentoring other health workers in the generalist setting, while being life-long learners themselves. However, their role in the community, was found to be more aspirational than real. Conclusions The study derived a set of principles for the practice of generalist doctors in sub-Saharan Africa based on the reported activities and approaches of the respondents. Patient-centred care using a biopsychosocial approach remains as a common core principle despite wide variations in context. Procedural and hospital care demands a higher level of skills particularly in rural areas, and a community orientation is desirable, but not widely practiced. The results have implications for the postgraduate training of family physicians in sub-Saharan Africa, and highlight questions regarding the realization of community-orientated primary care.Publishers' Versio

Development of a portfolio of learning for postgraduate family medicine training in South Africa: a Delphi study

<p>Abstract</p> <p>Background</p> <p>Within the 52 health districts in South Africa, the family physician is seen as the clinical leader within a multi-professional district health team. Family physicians must be competent to meet 90% of the health needs of the communities in their districts. The eight university departments of Family Medicine have identified five unit standards, broken down into 85 training outcomes, for postgraduate training. The family medicine registrar must prove at the end of training that all the required training outcomes have been attained. District health managers must be assured that the family physician is competent to deliver the expected service. The Colleges of Medicine of South Africa (CMSA) require a portfolio to be submitted as part of the uniform assessment of all registrars applying to write the national fellowship examinations. This study aimed to achieve a consensus on the contents and principles of the first national portfolio for use in family medicine training in South Africa.</p> <p>Methods</p> <p>A workshop held at the WONCA Africa Regional Conference in 2009 explored the purpose and broad contents of the portfolio. The 85 training outcomes, ideas from the WONCA workshop, the literature, and existing portfolios in the various universities were used to develop a questionnaire that was tested for content validity by a panel of 31 experts in family medicine in South Africa, via the Delphi technique in four rounds. Eighty five content items (national learning outcomes) and 27 principles were tested. Consensus was defined as 70% agreement. For those items that the panel thought should be included, they were also asked how to provide evidence for the specific item in the portfolio, and how to assess that evidence.</p> <p>Results</p> <p>Consensus was reached on 61 of the 85 national learning outcomes. The panel recommended that 50 be assessed by the portfolio and 11 should not be. No consensus could be reached on the remaining 24 outcomes and these were also omitted from the portfolio. The panel recommended that various types of evidence be included in the portfolio. The panel supported 26 of the 27 principles, but could not reach consensus on whether the portfolio should reflect on the relationship between the supervisor and registrar.</p> <p>Conclusion</p> <p>A portfolio was developed and distributed to the eight departments of Family Medicine in South Africa, and the CMSA, to be further tested in implementation.</p

The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences) the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs) per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction) in the macaque is more closely equivalent to that of the human. Conclusions This large panel of newly identified macaque SNPs enriched for functionally significant regions considerably expands our knowledge of genetic variation in the rhesus macaque. Comparative analysis reveals that this widespread, highly adaptable species is approximately three times as diverse as the human but more closely equivalent in damaging variation.http://deepblue.lib.umich.edu/bitstream/2027.42/112453/1/12863_2011_Article_1004.pd

Multi-platform Approach for Microbial Biomarker Identification Using Borrelia burgdorferi as a Model

The identification of microbial biomarkers is critical for the diagnosis of a disease early during infection. However, the identification of reliable biomarkers is often hampered by a low concentration of microbes or biomarkers within host fluids or tissues. We have outlined a multi-platform strategy to assess microbial biomarkers that can be consistently detected in host samples, using Borrelia burgdorferi, the causative agent of Lyme disease, as an example. Key aspects of the strategy include the selection of a macaque model of human disease, in vivo Microbial Antigen Discovery (InMAD), and proteomic methods that include microbial biomarker enrichment within samples to identify secreted proteins circulating during infection. Using the described strategy, we have identified 6 biomarkers from multiple samples. In addition, the temporal antibody response to select bacterial antigens was mapped. By integrating biomarkers identified from early infection with temporal patterns of expression, the described platform allows for the data driven selection of diagnostic targets

Internet-based medical education: a realist review of what works, for whom and in what circumstances

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