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.
Capsular contracture causes pain, poor cosmesis, and reoperations. This study analyzes its incidence and risk factors in a more modern treatment era.
Patients undergoing mastectomy with implant ...reconstruction from 2010 to 18 were reviewed. Univariate and multivariate analysis evaluated rates and risk factors for capsular contracture.
Among 451 patients, the majority underwent nipple-sparing mastectomy (262, 58.1%) with one-stage reconstruction (283, 62.7%) utilizing subpectoral implants (353, 77.4%) and acellular dermal matrix (354, 78.5%). Overall capsular contracture incidence was 9.8%; the rate after post-mastectomy radiation therapy (PMRT) was 18.7%, and 7.5% for patients without PMRT. Significant factors included neoadjuvant chemotherapy (P = 0.006), hematoma (P = 0.047), and PMRT (P = 0.001). Multivariate analysis showed that PMRT increased risk of capsular contracture (OR = 3.12, 95% CI 1.55–6.26, P = 0.001), and adjuvant chemotherapy was protective (OR = 0.289, 95% CI 0.114–0.731, P = 0.01).
Incidence of capsular contracture is lower than previously reported. Advancing therapeutic techniques may reduce the risk of this complication.
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•The incidence of capsular contracture is lower in the modern era.•Radiation therapy remains a significant risk factor.•New therapeutic techniques may reduce the risk for capsular contracture.
Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring ...dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. We reveal that 15% homogeneous dystrophin expression is sufficient to protect against eccentric contraction-induced injury. In addition, we demonstrate a >40% increase in specific isometric force following repeated administrations. Strikingly, we show that changes in muscle strength are proportional to dystrophin expression levels. These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model.
Antidepressants and old people Hammond, MargaretF; Evans, MavisE; Lye, Michael ...
The Lancet (British edition),
07/1993, Letnik:
342, Številka:
8865
Journal Article
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 -/-.
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
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.
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