49 research outputs found
Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy.
Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited.To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM.Qatar Foundation, National Institute for Health Research (Clinician Scientist Award Grant ID: CS-2015-15-023), Royal Australasian College of Surgeons (Reg Worcester Research Fellowship), Neurosurgical Society of Australasia (Research Scholarship), Wellcome Trust, Medical Research CouncilThis is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s40478-016-0359-
The Molecular Chaperone HSP90 Promotes Notch Signaling in the Germline of Caenorhabditis elegans
In a genetic screen to identify genes that promote GLP-1/Notch signaling in Caenorhabditis elegans germline stem cells, we found a single mutation, om40, defining a gene called ego-3. ego-3(om40) causes several defects in the soma and the germline, including paralysis during larval development, sterility, delayed proliferation of germline stem cells, and ectopic germline stem cell proliferation. Whole genome sequencing identified om40 as an allele of hsp-90, previously known as daf-21, which encodes the C. elegans ortholog of the cytosolic form of HSP90. This protein is a molecular chaperone with a central position in the protein homeostasis network, which is responsible for proper folding, structural maintenance, and degradation of proteins. In addition to its essential role in cellular function, HSP90 plays an important role in stem cell maintenance and renewal. Complementation analysis using a deletion allele of hsp-90 confirmed that ego-3 is the same gene. hsp-90(om40) is an IN conservative missense mutation of a highly conserved residue in the middle domain of HSP-90. RNA interference-mediated knockdown of hsp-90 expression partially phenocopied hsp-90(om40), confirming the loss-of-function nature ofhsp-90(om40). Furthermore, reduced HSP-90 activity enhanced the effect of reduced function of both the GLP-1 receptor and thedownstream LAG-1 transcription factor. Taken together, our results provide the first experimental evidence of an essential role for HSP90 inNotch signaling in development
Cybersex: Outercourse and the Enselfment of the Body
The increased popularity of the Internet invites the possibility of repackaging familiar activities in a new medium. Sex is one such activity—an age-old topic with a new cybertwist. The new technologies of computer-mediated communication allow us to examine the nature of human interaction in a uniquely disembodied environment that potentially transforms the nature of self, body, and situation. Sex—fundamentally a bodily activity—provides an ideal situation for examining these kinds of potential transformations. In the disembodied context of on-line interaction both bodies and selves are fluid symbolic constructs emergent in communication and are defined by sociocultural standards. Situations such as these are suggestive of issues related to contemporary transgressions of the empirical shell of the body, potentially reshaping body-to-self-to-social-world relationships
De Novo Identification of Single Nucleotide Mutations in Caenorhabditis elegans Using Array Comparative Genomic Hybridization
Array comparative genomic hybridization (aCGH) has been used primarily to detect copy-number variants between two genomes. Here we report using aCGH to detect single nucleotide mutations on oligonucleotide microarrays with overlapping 50-mer probes. This technique represents a powerful method for rapidly detecting novel homozygous single nucleotide mutations in any organism with a sequenced reference genome
Copy number variation in the genomes of twelve natural isolates of Caenorhabditis elegans
Background:
Copy number variation is an important component of genetic variation in higher eukaryotes. The extent of natural copy number variation in C. elegans is unknown outside of 2 highly divergent wild isolates and the canonical N2 Bristol strain.
Results:
We have used array comparative genomic hybridization (aCGH) to detect copy number variation in the genomes of 12 natural isolates of Caenorhabditis elegans. Deletions relative to the canonical N2 strain are more common in these isolates than duplications, and indels are enriched in multigene families on the autosome arms. Among the strains in our study, the Hawaiian and Madeiran strains (CB4856 and JU258) carry the largest number of deletions, followed by the Vancouver strain (KR314). Overall we detected 510 different deletions affecting 1136 genes, or over 5% of the genes in the canonical N2 genome. The indels we identified had a median length of 2.7 kb. Since many deletions are found in multiple isolates, deletion loci were used as markers to derive an unrooted tree to estimate genetic relatedness among the strains.
Conclusion:
Copy number variation is extensive in C. elegans, affecting over 5% of the genes in the genome. The deletions we have detected in natural isolates of C. elegans contribute significantly to the number of deletion alleles available to researchers. The relationships between strains are complex and different regions of the genome possess different genealogies due to recombination throughout the natural history of the species, which may not be apparent in studies utilizing smaller numbers of genetic markers.Science, Faculty ofZoology, Department ofNon UBCReviewedFacult
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LA Sustainable Water Project: Los Angeles River Watershed
The LA Sustainable Water Project: Los Angeles River Watershed report explores the potential to improve water quality standards while integrating complementary One Water Management practices that can increase potential local water supplies for the City of Los Angeles (the City) in the highly urbanized Los Angeles River (LAR) watershed.To assess the integrated water landscape in this watershed, the report also looks at current practices and future opportunities at the Donald C Tillman, LA Glendale, and Burbank Water Reclamation Plants (WRPs) and in the underlying Upper LA River Area (ULARA) adjudicated groundwater basins. Implementing watershed-scale best management practice programs to meet stormwater permit requirements will significantly improve water quality. However, additional mechanisms such as increasing Low Impact Development implementation and comprehensive source tracking and source control mechanisms will be required to potentially eliminate water quality exceedances. The 3 WRPs in the watershed currently discharge more than 30 million gallons per day of treated wastewater into the River; an increased focus on increasing local water supply could lead to a reduction in these discharges.The combination of increased stormwater capture and increased use of recycled water in the LAR watershed could lead to lower flows in the LAR and impact habitat and recreational uses; further study is needed to characterize potential impacts and identify optimal flows for the future of the LAR. The City is leading efforts in ULARA to increase the recharge of recycled water into theground by 30,000 acre feet per year and increase the volumes of remediated groundwater extracted by around 120,000 acre feet per year. This research demonstrates the complex interrelationships between all aspects of urban water management, including stormwater management and local water supply
Recommended from our members
LA Sustainable Water Project: Los Angeles River Watershed
The LA Sustainable Water Project: Los Angeles River Watershed report explores the potential to improve water quality standards while integrating complementary One Water Management practices that can increase potential local water supplies for the City of Los Angeles (the City) in the highly urbanized Los Angeles River (LAR) watershed.To assess the integrated water landscape in this watershed, the report also looks at current practices and future opportunities at the Donald C Tillman, LA Glendale, and Burbank Water Reclamation Plants (WRPs) and in the underlying Upper LA River Area (ULARA) adjudicated groundwater basins. Implementing watershed-scale best management practice programs to meet stormwater permit requirements will significantly improve water quality. However, additional mechanisms such as increasing Low Impact Development implementation and comprehensive source tracking and source control mechanisms will be required to potentially eliminate water quality exceedances. The 3 WRPs in the watershed currently discharge more than 30 million gallons per day of treated wastewater into the River; an increased focus on increasing local water supply could lead to a reduction in these discharges.The combination of increased stormwater capture and increased use of recycled water in the LAR watershed could lead to lower flows in the LAR and impact habitat and recreational uses; further study is needed to characterize potential impacts and identify optimal flows for the future of the LAR. The City is leading efforts in ULARA to increase the recharge of recycled water into theground by 30,000 acre feet per year and increase the volumes of remediated groundwater extracted by around 120,000 acre feet per year. This research demonstrates the complex interrelationships between all aspects of urban water management, including stormwater management and local water supply
Mercury, n-alkane and unresolved complex mixture hydrocarbon pollution in surface sediment across the rural–urban–estuarine continuum of the River Clyde, Scotland, UK
Surface sediments (n ¼ 85) from a 160-km river-estuarine transect of the Clyde,
UK, were analysed for total mercury (Hg), saturated hydrocarbons and unresolved complex
mixtures (UCMs) of hydrocarbons. Results show that sediment-Hg concentration ranges from 0.01
to 1.38 mg kg–1 (mean 0.20 mg kg–1) and a spatial trend in Hg-content low–high–low–high, from
freshwater source, to Glasgow, to estuary, is evident. In summary, sediment-Hg content is low
in the upper Clyde (mean of 0.05 Hg mg kg–1), whereas sediments from the Clyde in urbanised
Glasgow have higher Hg concentrations (0.04 to 1.26 mg kg–1; mean 0.45mgkg–1), and the
inner estuary sediments contain less Hg (mean 0.06 mg kg–1). The highest mean sediment Hg
(0.65 mg kg–1) found in the outer estuary is attributed to historical anthropogenic activities. A significant
positive Spearman correlation between Hg and total organic carbon is observed throughout the
river estuary (0.86; P < 0.001). Comparison with Marine Scotland guidelines suggests that no sites
exceed the 1.5 mg kg–1 criterion (Action Level 2); 22 fall between 0.25 and 1.5 mg kg–1 dry wt.
(Action Level 1) and 63 are of no immediate concern (<0.25 mg kg–1 dry wt.). Saturated (n-alkane)
hydrocarbons in the upper Clyde are of natural terrestrial origin. By contrast, the urbanised Glasgow
reaches and outer estuary are characterised by pronounced and potentially toxic UCM concentrations
in sediments (380–914 mg/kg and 103–247 mg kg–1, respectively), suggesting anthropogenic
inputs such as biodegraded crude oil, sewage discharge and/or urban run-off