1,414 research outputs found
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Teeth are unique to the individual just like fingerprints. I paint human sets of teeth and their stages of mutations to explore the connections between our own naturally occurring inner mutations and our science-enduced rebuilding of these structures from stem cells. These duplicated and mirrored forms originate from teeth stem cells and their ability to regenerate our teeth. I also use teeth in my work because they represent us as a whole yet erase the boundary line of gender; while they still follow a naturally occurring, common process. So we can all relate to teeth, yet they are very personal identifiers
Clustering Multiple Sclerosis Medication Sequence Data with Mixture Markov Chain Analysis with covariates using Multiple Simplex Constrained Optimization Routine (MSiCOR)
Multiple sclerosis (MS) is an autoimmune disease of the central nervous
system that causes neurodegeneration. While disease-modifying therapies (DMTs)
reduce inflammatory disease activity and delay worsening disability in MS,
there are significantly varying treatment responses across people with MS
(pwMS). pwMS often receive serial monotherapies of DMTs. Here, we propose a
novel method to cluster pwMS according to the sequence of DMT prescriptions and
associated clinical features (covariates). This is achieved via a mixture
Markov chain analysis with covariates, where the sequence of prescribed DMTs
for each patient is modeled as a Markov chain. Given the computational
challenges to maximize the mixture likelihood on the constrained parameter
space, we develop a pattern search-based global optimization technique which
can optimize any objective function on a collection of simplexes and shown to
outperform other related global optimization techniques. In simulation
experiments, the proposed method is shown to outperform the
Expectation-Maximization (EM) algorithm based method for clustering sequence
data without covariates. Based on the analysis, we divided MS patients into 3
clusters: inferon-beta dominated, multi-DMTs, and natalizumab dominated.
Further cluster-specific summaries of relevant covariates indicate patient
differences among the clusters. This method may guide the DMT prescription
sequence based on clinical features
Long-term calorie restriction in humans is not associated with indices of delayed immunologic aging: A descriptive study.
BACKGROUND: Delayed immunologic aging is purported to be a major mechanism through which calorie restriction (CR) exerts its anti-aging effects in non-human species. However, in non-obese humans, the effect of CR on the immune system has been understudied relative to its effects on the cardiometabolic system. OBJECTIVE: To examine whether CR is associated with delayed immunologic aging in non-obese humans. METHODS: We tested whether long-term CR practitioners (average 10.03 years of CR) evidenced decreased expression of T cell immunosenescence markers and longer immune cell telomeres compared to gender-, race/ethnicity-, age-, and education-matched "healthy" Body Mass Index (BMI) and "overweight"/"obese" BMI groups. RESULTS: Long-term human CR practitioners had lower BMI (p <  0.001) and fasting glucose (p <  0.001), as expected. They showed similar frequencies of pre-senescent cells (CD8+CD28- T cells and CD57 and PD-1 expressing T cells) to the comparison groups. Even after adjusting for covariates, including cytomegalovirus status, we observed shorter peripheral blood mononuclear cell telomeres in the CR group (p = 0.012) and no difference in granulocyte telomeres between groups (p = 0.42). CONCLUSIONS: We observed no clear evidence that CR as it is currently practiced in humans delays immune aging related to telomere length or T cell immunosenescent markers
Linear B-cell epitopes of the NS3-NS4-NS5 proteins of the hepatitis C virusas modeled with synthetic peptides
AbstractA set of 150 synthetic peptides spanning the proteins NS3-NS4-NS5 of the hepatitis C virus (HCV) was synthesizedand tested with a panel of 20 sera obtained from HCV-infected patients. Of 62 peptides prepared from the NS3 region, none exhibited strong antigenic reactivity. Rather, five peptides from this region demonstrated specific reactivity with only 5–10% of anti-HCV-positive sera. Nonetheless, it is well known that the NS3 region contains strong antigenic epitopes. These epitopes appear to be modeled in a functionally active manner with recombinant proteins and cannot be mimicked properly with short synthetic peptides. This finding suggests that the major NS3 antigenic epitopes are conformationally dependent. Seven of 20 peptides prepared from the NS4 region were immunoreactive. Five peptides from this region demonstrated very strong HCV-specific antigenic reactivity. Four of the five peptides belong to the recognized immunoreactive 5-1-1 region located inside the C100-3 antigen. One peptide demonstrating immunoreactivity with approximately 90% of anti-HCV-positive sera was found outside the C100-3 region at the C-terminal part of the NS4 protein. Of 68 peptides synthesized from the NS5 protein, 30 were immunoreactive. Six of the 30 demonstrated immunoreactivity with 35–50% of anti-HCV-positive sera. Thus, the NS4 and NS5 regions of the HCV polyprotein contain a large number of specific, broadly reactive, linear antigenic epitopes. The highly antigenic reactivity of the NS5 region suggests that this protein may have significant diagnostic potential
Chronic Stress Elevates Telomerase Activity in Rats
The enzyme telomerase lengthens telomeres—protective structures containing repetitive DNA sequences at chromosome ends. Telomere shortening is associated with diseases of ageing in mammals. Chronic stress has been related to shorter immune-cell telomeres, but telomerase activity under stress may be low, permitting telomere loss, or high, partially attenuating it. We developed an experimental model to examine the impacts of extended unpredictable stress on telomerase activity in male rats. Telomerase activity was 54 per cent higher in stressed rats than in controls, and associated with stress-related physiological and behavioural outcomes. This significant increase suggests a potential mechanism for resilience to stress-related replicative senescence
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