Genetically Determined Height and Risk of Non-hodgkin Lymphoma

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00–1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01–1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes

Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes

AIM: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. METHODS: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. RESULTS: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, P = 1.6 × 10(-6)) and FL (β = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, P = 2.4 × 10(-5)). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. CONCLUSION: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk

The conservation of a 19th Century giant deer display skeleton for public exhibition

Following a mishap, a 19th Century mounted giant deer was subjected to a detailed osteological assessment and conservation treatment which required both structura repair and the extensive modeling of broken and missing skeletal components. The historic mounting system and plinth were largely intact and structurally safe for the skeleton and so these could be retained along with any historic restorations deemed sound and non-damaging. The original skull suffered irreparable damage and both antlers were detached from the specimen. A replacement skull was acquired but it was necessary to attach the original antlers to the new skull in a manner both structurally sound and aesthetically accurate enough for the deer to be placed backon open display. After testing commonly used conservation-grade filler materials suitable for fabricating missing skeletal components, losses to the vertebra and the ribcage were re-built using epoxy resin bulked to putty consistency with phenolicmicroballoons and applied over barrier layers of Paraloid B72 and Japanese tissue. All losses were in-painted with earth pigments in Paraloid B72 before rearticulation. The unique role of this specimen determined the conservation approaches adopted and included a balanced consideration of conservation ethical concerns, client expectations, future structural stability, aesthetic impact and the limitations of the future display location

The conservation of a 19th Century giant deer display skeleton for public exhibition

Following a mishap, a 19th Century mounted giant deer was subjected to a detailed osteological assessment and conservation treatment which required both structura repair and the extensive modeling of broken and missing skeletal components. The historic mounting system and plinth were largely intact and structurally safe for the skeleton and so these could be retained along with any historic restorations deemed sound and non-damaging. The original skull suffered irreparable damage and both antlers were detached from the specimen. A replacement skull was acquired but it was necessary to attach the original antlers to the new skull in a manner both structurally sound and aesthetically accurate enough for the deer to be placed backon open display. After testing commonly used conservation-grade filler materials suitable for fabricating missing skeletal components, losses to the vertebra and the ribcage were re-built using epoxy resin bulked to putty consistency with phenolicmicroballoons and applied over barrier layers of Paraloid B72 and Japanese tissue. All losses were in-painted with earth pigments in Paraloid B72 before rearticulation. The unique role of this specimen determined the conservation approaches adopted and included a balanced consideration of conservation ethical concerns, client expectations, future structural stability, aesthetic impact and the limitations of the future display location

Altered Immunomodulatory Responses in the CX3CL1/CX3CR1 Axis Mediated by hMSCs in an Early In Vitro SOD1^G93A Model of ALS

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron (MN) disease characterized by progressive MN loss and muscular atrophy resulting in rapidly progressive paralysis and respiratory failure. Human mesenchymal stem/stromal cell (hMSC)-based therapy has been suggested to prolong MN survival via secretion of growth factors and modulation of cytokines/chemokines. We investigated the effects of hMSCs and a hMSC-conditioned medium (CM) on Cu/Zn superoxidase dismutase 1G93A (SOD1G93A) transgenic primary MNs. We found that co-culture of hMSCs and MNs resulted in slightly higher MN numbers, but did not protect against staurosporine (STS)-induced toxicity, implying marginal direct trophic effects of hMSCs. Aiming to elucidate the crosstalk between hMSCs and MNs in vitro, we found high levels of vascular endothelial growth factor (VEGF) and C-X3-C motif chemokine 1 (CX3CL1) in the hMSC secretome. Co-culture of hMSCs and MNs resulted in altered gene expression of growth factors and cytokines/chemokines in both MNs and hMSCs. hMSCs showed upregulation of CX3CL1 and its receptor CX3CR1 and downregulation of interleukin-1 β (IL1β) and interleukin-8 (IL8) when co-cultured with SOD1G93A MNs. MNs, on the other hand, showed upregulation of growth factors as well as CX3CR1 upon hMSC co-culture. Our results indicate that hMSCs only provide moderate trophic support to MNs by growth factor gene regulation and may mediate anti-inflammatory responses through the CX3CL1/CX3CR1 axis, but also increase expression of pro-inflammatory cytokines, which limits their therapeutic potential

Umwelt Schule als Objekt von Beeintraechtigung und Zerstoerung (DFG-Projekt) 1. Arbeitsbericht

UuStB Koeln(38)-8206961 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Umwelt Schule als Objekt von Beeintraechtigung und Zerstoerung (DFG-Projekt) 2. Arbeitsbericht

UuStB Koeln(38)-8307013 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman