Comparative analysis of pseudogenes across three phyla

Pseudogenes are degraded fossil copies of genes. Here, we report a comparison of pseudogenes spanning three phyla, leveraging the completed annotations of the human, worm, and fly genomes, which we make available as an online resource. We find that pseudogenes are lineage specific, much more so than proteincoding genes, reflecting the different remodeling processes marking each organism’s genome evolution. The majority of human pseudogenes are processed, resulting from a retrotranspositional burst at the dawn of the primate lineage. This burst can be seen in the largely uniform distribution of pseudogenes across the genome, their preservation in areas with low recombination rates, and their preponderance in highly expressed gene families. In contrast, worm and fly pseudogenes tell a story of numerous duplication events. In worm, these duplications have been preserved through selective sweeps, so we see a large number of pseudogenes associated with highly duplicated families such as chemoreceptors. However, in fly, the large effective population size and high deletion rate resulted in a depletion of the pseudogene complement. Despite large variations between these species, we also find notable similarities. Overall, we identify a broad spectrum of biochemical activity for pseudogenes, with the majority in each organism exhibiting varying degrees of partial activity. In particular, we identify a consistent amount of transcription (∼15%) across all species, suggesting a uniform degradation process. Also, we see a uniform decay of pseudogene promoter activity relative to their coding counterparts and identify a number of pseudogenes with conserved upstream sequences and activity, hinting at potential regulatory roles

"I really should've gone to the doctor": older adults and family caregivers describe their experiences with community-acquired pneumonia

BACKGROUND: Responding to acute illness symptoms can often be challenging for older adults. The primary objective of this study was to describe how community-dwelling older adults and their family members responded to symptoms of community-acquired pneumonia (CAP). METHODS: A qualitative study that used face-to-face semi-structured interviews to collect data from a purposeful sample of seniors aged 60+ and their family members living in a mid-sized Canadian city. Data analysis began with descriptive and interpretive coding, then advanced as the research team repeatedly compared emerging thematic categories to the raw data. Searches for disconfirming evidence and member checking through focus groups provided additional data and helped ensure rigour. RESULTS: Community-acquired pneumonia symptoms varied greatly among older adults, making decisions to seek care difficult for them and their family members. Both groups took varying amounts of time as they attempted to sort out what was wrong and then determine how best to respond. Even after they concluded something was wrong, older adults with confirmed pneumonia continued to wait for days, to over a week, before seeking medical care. Participants provided diverse reasons for this delay, including fear, social obligations (work, family, leisure), and accessibility barriers (time, place, systemic). Several older adults and family members regretted their delays in seeking help. CONCLUSION: Treatment-seeking delay is a variable, multi-phased decision-making process that incorporates symptom assessment plus psychosocial and situational factors. Public health and health care professionals need to educate older adults about the potential causes and consequences of unnecessary waits. Such efforts may reduce the severity of community-acquired pneumonia upon presentation at clinics and hospitals, and that, in turn, could potentially improve health outcomes

Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA

Breaking of left-right symmetry in mouse embryos requires fluid flow at the node, but the precise action of the flow has remained unknown. Here we show that the left-right asymmetry of Cerl2 expression around the node, a target of the flow, is determined post-transcriptionally by decay of Cerl2 mRNA in a manner dependent on its 3' untranslated region. Cerl2 mRNA is absent specifically from the apical region of crown cells on the left side of the node. Preferential decay of Cerl2 mRNA on the left is initiated by the leftward flow and further enhanced by the operation of Wnt-Cerl2 interlinked feedback loops, in which Wnt3 upregulates Wnt3 expression and promotes Cerl2 mRNA decay, whereas Cerl2 promotes Wnt degradation. Mathematical modelling and experimental data suggest that these feedback loops behave as a bistable switch that can amplify in a noise-resistant manner a small bias conferred by fluid flow.Ministry of Education, Culture, Sports, Science, and Technology of Japan; Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation (JST); GCOE of Osaka University; FCTinfo:eu-repo/semantics/publishedVersio

Description of an aerodynamic levitation apparatus with applications in Earth sciences

<p>Abstract</p> <p>Background</p> <p>In aerodynamic levitation, solids and liquids are floated in a vertical gas stream. In combination with CO₂-laser heating, containerless melting at high temperature of oxides and silicates is possible. We apply aerodynamic levitation to bulk rocks in preparation for microchemical analyses, and for evaporation and reduction experiments.</p> <p>Results</p> <p>Liquid silicate droplets (~2 mm) were maintained stable in levitation using a nozzle with a 0.8 mm bore and an opening angle of 60°. The gas flow was ~250 ml min^-1. Rock powders were melted and homogenized for microchemcial analyses. Laser melting produced chemically homogeneous glass spheres. Only highly (e.g. H₂O) and moderately volatile components (Na, K) were partially lost. The composition of evaporated materials was determined by directly combining levitation and inductively coupled plasma mass spectrometry. It is shown that the evaporated material is composed of Na > K >> Si. Levitation of metal oxide-rich material in a mixture of H₂and Ar resulted in the exsolution of liquid metal.</p> <p>Conclusions</p> <p>Levitation melting is a rapid technique or for the preparation of bulk rock powders for major, minor and trace element analysis. With exception of moderately volatile elements Na and K, bulk rock analyses can be performed with an uncertainty of ± 5% relative. The technique has great potential for the quantitative determination of evaporated materials from silicate melts. Reduction of oxides to metal is a means for the extraction and analysis of siderophile elements from silicates and can be used to better understand the origin of chondritic metal.</p

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

Epidemiology of neurodegenerative diseases in sub-Saharan Africa: a systematic review

BACKGROUND:Sub-Saharan African (SSA) countries are experiencing rapid transitions with increased life expectancy. As a result the burden of age-related conditions such as neurodegenerative diseases might be increasing. We conducted a systematic review of published studies on common neurodegenerative diseases, and HIV-related neurocognitive impairment in SSA, in order to identify research gaps and inform prevention and control solutions. METHODS: We searched MEDLINE via PubMed, 'Banque de Donnees de Sante Publique' and the database of the 'Institut d'Epidemiologie Neurologique et de Neurologie Tropicale' from inception to February 2013 for published original studies from SSA on neurodegenerative diseases and HIV-related neurocognitive impairment. Screening and data extraction were conducted by two investigators. Bibliographies and citations of eligible studies were investigated. RESULTS: In all 144 publications reporting on dementia (n=49 publications, mainly Alzheimer disease), Parkinsonism (PD, n=20), HIV-related neurocognitive impairment (n=47), Huntington disease (HD, n=19), amyotrophic lateral sclerosis (ALS, n=15), cerebellar degeneration (n=4) and Lewy body dementia (n=1). Of these studies, largely based on prevalent cases from retrospective data on urban populations, half originated from Nigeria and South Africa. The prevalence of dementia (Alzheimer disease) varied between <1% and 10.1% (0.7% and 5.6%) in population-based studies and from <1% to 47.8% in hospital-based studies. Incidence of dementia (Alzheimer disease) ranged from 8.7 to 21.8/1000/year (9.5 to 11.1), and major risk factors were advanced age and female sex. HIV-related neurocognitive impairment's prevalence (all from hospital-based studies) ranged from <1% to 80%. Population-based prevalence of PD and ALS varied from 10 to 235/100,000, and from 5 to 15/100,000 respectively while that for Huntington disease was 3.5/100,000. Equivalent figures for hospital based studies were the following: PD (0.41 to 7.2%), ALS (0.2 to 8.0/1000), and HD (0.2/100,000 to 46.0/100,000). CONCLUSIONS: The body of literature on neurodegenerative disorders in SSA is large with regard to dementia and HIV-related neurocognitive disorders but limited for other neurodegenerative disorders. Shortcomings include few population-based studies, heterogeneous diagnostic criteria and uneven representation of countries on the continent. There are important knowledge gaps that need urgent action, in order to prepare the sub-continent for the anticipated local surge in neurodegenerative diseases