The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic ...annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.
The capacity to fully replace teeth continuously makes zebrafish an attractive model to explore regeneration and tooth development. The requirement of attachment bone for the appearance of ...replacement teeth has been hypothesized but not yet investigated. The transcription factor sp7 (osterix) is known in mammals to play an important role during odontoblast differentiation and root formation. Here we study tooth replacement in the absence of attachment bone using sp7 zebrafish mutants. We analysed the pattern of tooth replacement at different stages of development and demonstrated that in zebrafish lacking sp7, attachment bone is never present, independent of the stage of tooth development or fish age, yet replacement is not interrupted. Without bone of attachment we observed abnormal orientation of teeth, and abnormal connection of pulp cavities of predecessor and replacement teeth. Mutants lacking sp7 show arrested dentinogenesis, with non-polarization of odontoblasts and only a thin layer of dentin deposited. Osteoclast activity was observed in sp7 mutants; due to the lack of bone of attachment, remodelling was diminished but nevertheless present along the pharyngeal bone. We conclude that tooth replacement is ongoing in the sp7 mutant despite poor differentiation and defective attachment. Without bone of attachment tooth orientation and pulp organization are compromised.
•Attachment of bone is never present in zebrafish lacking sp7.•sp7-/- show arrested dentinogenesis, with non-polarization of odontoblasts and with only a thin layer of dentin.•Tooth replacement is not interrupted in the absence of bone of attachment, or eruption of predecessor tooth.•defective differentiation of the tooth does not prevent a successional tooth to be formed.•Abnormal orientation of teeth and pulp connection between predecessor and replacement tooth were often observed in sp7 -/-.
Abstract
Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick,
Ixodes scapularis
(Say), which vectors pathogens that cause ...Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.
Transit time distributions (TTDs) exert important controls on biogeochemical processes in watershed systems. TTDs are often assumed to follow time‐invariant exponential, lognormal, or heavy‐tailed ...power law distributions in headwater or low‐order streams. However, under dynamic hydrological forcing, transit time could exhibit more complex distribution patterns with strong spatial and temporal variability. In this study, we used a numerical particle tracking approach to characterize TTDs along the Hanford Reach of the Columbia River under the influences of river stage fluctuations and evaluate the associated effects on biogeochemical reaction potentials within the river corridor. Particle tracking was conducted using velocity fields simulated by high‐resolution three‐dimensional groundwater flow models that capture both the river stage fluctuations and physical heterogeneity. Our results revealed that multifrequency flow variations led to multimodal TTDs that varied in time and space. Such characteristics can only be captured by multiyear numerical simulations supported by multiyear field monitoring. Dam‐induced high‐frequency (subweekly) flow variations increased additional hydrologic exchange flows with short (subweekly) transit times, which accounted for up to 44% of reactant consumption in the river corridor along the Hanford Reach. The dam‐induced river stage fluctuations have more significant impacts on faster biogeochemical reactions because they cause a larger fraction of shorter transit times. Numerical particle tracking provides an efficient alternative for characterizing TTDs for large complex systems where in situ field experiments are not feasible. Such a numerical approach is thus essential for improving large‐scale biogeochemical modeling from watersheds to basins.
Key Points
River stage fluctuations lead to highly dynamic, multimodal transit time distributions
Dam‐induced high‐frequency river stage variations have higher impacts on faster biogeochemical reactions
Numerical particle tracking can effectively characterize complex transit time distributions
Development of appropriate dendritic arbors is crucial for neuronal information transfer. We show, using seizure-related gene 6 (
sez-6) null mutant mice, that Sez-6 is required for normal dendritic ...arborization of cortical neurons. Deep-layer pyramidal neurons in the somatosensory cortex of
sez-6 null mice exhibit an excess of short dendrites, and cultured cortical neurons lacking Sez-6 display excessive neurite branching. Overexpression of individual Sez-6 isoforms in knockout neurons reveals opposing actions of membrane-bound and secreted Sez-6 proteins, with membrane-bound Sez-6 exerting an antibranching effect under both basal and depolarizing conditions. Layer V pyramidal neurons in knockout brain slices show reduced excitatory postsynaptic responses and a reduced dendritic spine density, reflected by diminished punctate staining for postsynaptic density 95 (PSD-95). In behavioral tests, the
sez-6 null mice display specific exploratory, motor, and cognitive deficits. In conclusion, cell-surface protein complexes involving Sez-6 help to sculpt the dendritic arbor, in turn enhancing synaptic connectivity.
Our objective was to make recommendations intended to reduce the rate of opioid misuse and overdose for a particularly high-risk group of people with traumatic brain injury (TBI). A consensus process ...conducted with TBI researchers and expert practitioners developed practical recommendations to inform prescribing of opioids for people with TBI. After determining key general principles for prescribing opioids for people with TBI, 6 TBI-specific recommendations were developed, 1 for acute pain in the agitated patient with TBI, 3 recommendations to be considered before prescribing an opioid, and 2 for follow-up and use by mental health and substance use disorder providers. While there is much needed research to examine the relationship between opioid misuse and TBI, the present recommendations provide at least some clinical considerations that might serve to prevent further deaths among a high-risk group.
Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory ...cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity).
The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings.
Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses.
Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.
Growing Contributions of Nano in 2020 Brinker, C. Jeffrey; Buriak, Jillian M; Chan, Warren C. W ...
ACS nano,
12/2020, Letnik:
14, Številka:
12
Journal Article
In March 2012, The Elizabeth Glaser Pediatric AIDS Foundation trained maternal and child health workers in Southern Province of Zambia to use a new rapid syphilis test (RST) during routine antenatal ...care. A recent study by Bonawitz et al. (2014) evaluated the impact of this roll out in Kalomo District. This paper estimates the costs and cost-effectiveness from the provider's perspective under the actual conditions observed during the first year of the RST roll out.
Information on materials used and costs were extracted from program records. A decision-analytic model was used to evaluate the costs (2012 USD) and cost-effectiveness. Basic parameters needed for the model were based on the results from the evaluation study.
During the evaluation study, 62% of patients received a RST, and 2.8% of patients tested were positive (and 10.4% of these were treated). Even with very high RST sensitivity and specificity (98%), true prevalence of active syphilis would be substantially less (estimated at <0.7%). For 1,000 new ANC patients, costs of screening and treatment were estimated at $2,136, and the cost per avoided disability-adjusted-life year lost (DALY) was estimated at $628. Costs change little if all positives are treated (because prevalence is low and treatment costs are small), but the cost-per-DALY avoided falls to just $66. With full adherence to guidelines, costs increase to $3,174 per 1,000 patients and the cost-per-DALY avoided falls to $60.
Screening for syphilis is only useful for reducing adverse birth outcomes if patients testing positive are actually treated. Even with very low prevalence of syphilis (a needle in the haystack), cost effectiveness improves dramatically if those found positive are treated; additional treatment costs little but DALYs avoided are substantial. Without treatment, the needle is essentially found and thrown back into the haystack.
Tomato Cf genes confer resistance to C. fulvum, reside in complex loci carrying multiple genes, and encode predicted membrane-bound proteins with extracytoplasmic leucine-rich repeats. At least two ...Cf-9 homologs confer novel C. fulvum resistance specificities. Comparison of 11 genes revealed 7 hypervariable amino acid positions in a motif of the leucine-rich repeats predicted to form a beta-strand/beta-turn in which the hypervariable residues are solvent exposed and potentially contribute to recognition specificity. Higher nonsynonymous than synonymous substitution rates in this region imply selection for sequence diversification. We propose that the level of polymorphism between intergenic regions determines the frequency of sequence exchange between the tandemly repeated genes. This permits sufficient exchange to generate sequence diversity but prevents sequence homogenization.
PDF
