Differential binding patterns of anti-sulfatide antibodies to glial membranes

Sulfatide is a major glycosphingolipid in myelin and a target for autoantibodies in autoimmune neuropathies. However neuropathy disease models have not been widely established, in part because currently available monoclonal antibodies to sulfatide may not represent the diversity of anti-sulfatide antibody binding patterns found in neuropathy patients. We sought to address this issue by generating and characterising a panel of new anti-sulfatide monoclonal antibodies. These antibodies have sulfatide reactivity distinct from existing antibodies in assays and in binding to peripheral nerve tissues and can be used to provide insights into the pathophysiological roles of anti-sulfatide antibodies in demyelinating neuropathies

A novel cellular pathway of antigen presentation and CD4 T cell activation in vivo

Dendritic cell activation of CD4 T cells in the lymph node draining a site of infection or vaccination is widely considered the central event in initiating adaptive immunity. The accepted dogma is that this occurs by stimulating local activation and antigen acquisition by dendritic cells, with subsequent lymph node migration, however the generalizability of this mechanism is unclear. Here we show that in some circumstances antigen can bypass the injection site inflammatory response, draining freely and rapidly to the lymph nodes where it interacts with subcapsular sinus (SCS) macrophages resulting in their death. Debris from these dying SCS macrophages is internalized by monocytes recruited from the circulation. This coordinated response leads to antigen presentation by monocytes and interactions with naïve CD4 T cells that can drive the initiation of T cell and B cell responses. These studies demonstrate an entirely novel pathway leading to initiation of adaptive immune responses in vivo

The visual, the auditory and the haptic – A user study on combining modalities in virtual worlds

Fröhlich J, Wachsmuth I. The visual, the auditory and the haptic – A user study on combining modalities in virtual worlds. In: Shumaker R, ed. Virtual Augmented and Mixed Reality. Designing and Developing Augmented and Virtual Environments. Lecture Notes in Computer Science. Vol 8021. Berlin, Heidelberg: Springer Berlin Heidelberg; 2013: 159-168.In order to make a step further towards understanding the impact of multi-modal stimuli in Virtual Reality we conducted a user study with 80 participants performing tasks in a virtual pit environment. Participants were divided into four groups, each presented a different combination of multi-sensory stimuli. Those included real-time 3D graphics, audio stimuli (ambient, static and event sounds), and haptics consisting of wind and tactile feedback when touching objects. A presence questionnaire was used to evaluate subjectively reported presence on the one hand, and on the other physiological sensors were used to measure heart rate and skin conductance as an objective measure. Results strongly indicate that an increase of modalities does not automatically result in an increase of presence

Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns

ABSTRACT: BACKGROUND: Aberrant CpG island promoter DNA hypermethylation is frequently observed in cancer and is believed to contribute to tumor progression by silencing the expression of tumor suppressor genes. Previously, we observed that promoter hypermethylation in breast cancer reflects cell lineage rather than tumor progression and occurs at genes that are already repressed in a lineage-specific manner. To investigate the generality of our observation we analyzed the methylation profiles of 1,154 cancers from 7 different tissue types. RESULTS: We find that 1,009 genes are prone to hypermethylation in these 7 types of cancer. Nearly half of these genes varied in their susceptibility to hypermethylation between different cancer types. We show that the expression status of hypermethylation prone genes in the originator tissue determines their propensity to become hypermethylated in cancer; specifically, genes that are normally repressed in a tissue are prone to hypermethylation in cancers derived from that tissue. We also show that the promoter regions of hypermethylation-prone genes are depleted of repetitive elements and that DNA sequence around the same promoters is evolutionarily conserved. We propose that these two characteristics reflect tissue-specific gene promoter architecture regulating the expression of these hypermethylation prone genes in normal tissues. CONCLUSIONS: As aberrantly hypermethylated genes are already repressed in pre-cancerous tissue, we suggest that their hypermethylation does not directly contribute to cancer development via silencing. Instead aberrant hypermethylation reflects developmental history and the perturbation of epigenetic mechanisms maintaining these repressed promoters in a hypomethylated state in normal cells.Publisher PDFPeer reviewe

Evaluating Barriers to Health in Homebound Individuals

Introduction. Homebound individuals in Vermont often have multiple comorbidities and can face significant food insecurity. In response to this problem, the Chittenden County Emergency Food Shelf (CEFS) Homebound Delivery Program (HDP) delivers one week of food per month to 130 individuals in Chittenden County, Vermont.https://scholarworks.uvm.edu/comphp_gallery/1084/thumbnail.jp

The Ionization Fraction in Dense Molecular Gas II: Massive Cores

We present an observational and theoretical study of the ionization fraction in several massive cores located in regions that are currently forming stellar clusters. Maps of the emission from the J = 1-> O transitions of C18O, DCO+, N2H+, and H13CO+, as well as the J = 2 -> 1 and J = 3 -> 2 transitions of CS, were obtained for each core. Core densities are determined via a large velocity gradient analysis with values typically 10^5 cm^-3. With the use of observations to constrain variables in the chemical calculations we derive electron fractions for our overall sample of 5 cores directly associated with star formation and 2 apparently starless cores. The electron abundances are found to lie within a small range, -6.9 < log10(x_e) < -7.3, and are consistent with previous work. We find no difference in the amount of ionization fraction between cores with and without associated star formation activity, nor is any difference found in electron abundances between the edge and center of the emission region. Thus our models are in agreement with the standard picture of cosmic rays as the primary source of ionization for molecular ions. With the addition of previously determined electron abundances for low mass cores, and even more massive cores associated with O and B clusters, we systematically examine the ionization fraction as a function of star formation activity. This analysis demonstrates that the most massive sources stand out as having the lowest electron abundances (x_e < 10^-8).Comment: 35 pages (8 figures), using aaspp4.sty, to be published in Astrophysical Journa

Comparative analysis of affinity-based 5-hydroxymethylation enrichment techniques

The epigenetic modification of 5-hydroxymethylcytosine (5hmC) is receiving great attention due to its potential role in DNA methylation reprogramming and as a cell state identifier. Given this interest, it is important to identify reliable and cost-effective methods for the enrichment of 5hmC marked DNA for downstream analysis. We tested three commonly used affinity-based enrichment techniques; (i) antibody, (ii) chemical capture and (iii) protein affinity enrichment and assessed their ability to accurately and reproducibly report 5hmC profiles in mouse tissues containing high (brain) and lower (liver) levels of 5hmC. The protein-affinity technique is a poor reporter of 5hmC profiles, delivering 5hmC patterns that are incompatible with other methods. Both antibody and chemical capture-based techniques generate highly similar genome-wide patterns for 5hmC, which are independently validated by standard quantitative PCR (qPCR) and glucosyl-sensitive restriction enzyme digestion (gRES-qPCR). Both antibody and chemical capture generated profiles reproducibly link to unique chromatin modification profiles associated with 5hmC. However, there appears to be a slight bias of the antibody to bind to regions of DNA rich in simple repeats. Ultimately, the increased specificity observed with chemical capture-based approaches makes this an attractive method for the analysis of locus-specific or genome-wide patterns of 5hm

Do children with neurological disabilities use more inpatient resources: an observational study.

BACKGROUND: Advances in healthcare have improved the survival of children with neurological disabilities (ND). Studies in the US have shown that children with ND use a substantial proportion of resources in children's hospitals, however, little research has been conducted in the UK. We aimed to test the hypothesis that children with neurological disabilities use more inpatient resources than children without neurological disabilities, and to quantify any significant differences in resource use. METHODS: A retrospective observational study was conducted, looking at the number of hospital admissions, total inpatient days and the reason for admissions for paediatric inpatients from January 1st to March 31st 2015. Inpatients were assigned into one of three groups: children without ND, children with one ND, and children with more than one ND. RESULTS: The sample population included 942 inpatients (mean age 6y 6mo). Children with at least one ND accounted for 15.3% of the inpatients, 17.7% of total hospital inpatient admission episodes, and 27.8% of the total inpatients days. Neurological disability had a statistically significant effect on total hospital admissions (p < 0.001). Neurological disability also had a statistically significant effect on total inpatient days (p < 0.001). Neurological disability increased the length of inpatient stay across medicine, specialties, and surgery. CONCLUSIONS: Children with ND had more frequent hospital admission episode and longer inpatient stays. We identified a smaller group within this population, with arguably more complex neurological disabilities, children with more than one ND. This group had the highest number of admissions and longest inpatient stays. More frequent hospital admissions and longer inpatient stays may place children with ND at greater risk of the adverse effects of hospitalisations. We recommend further investigations looking at each the effects of the different categories of ND on inpatient resource use, and repeat of this study at a national level and over a longer period of time