Absence of a dose-rate effect in the transformation of C3H 10T1/2 cells by α-particles

The findings of Hill et al. (1984) on the greatly enhanced transformation frequencies at very low dose rates of fission neutrons induced us to perform an analogous study with -particles at comparable dose rates. Transformation frequencies were determined with γ-rays at high dose rate (0·5 Gy/min), and with -particles at high (0·2 Gy/min) and at low dose rates (0·83-2·5 mGy/min) in the C3H 10T1/2 cell system. α-particles were substantially more effective than γ-rays, both for cell inactivation and for neoplastic transformation at high and low dose rates. The relative biological effectiveness (RBE) for cell inactivation and for neoplastic transformation was of similar magnitude, and ranged from about 3 at an -particle dose of 2 Gy to values of the order of 10 at 0·25 Gy. In contrast to the experiments of Hill et al. (1984) with fission neutrons, no increased transformation frequencies were observed when the -particle dose was protracted over several hours

Long-lived tumor-associated macrophages in glioma

BACKGROUND: The tumor microenvironment (TME) plays a major tumor-supportive role in glioma. In particular, tumor-associated macrophages (TAMs), which can make up to one third of the tumor mass, actively support tumor growth, invasion and angiogenesis. Predominantly alternatively activated (M2-polarized) TAMs are found in late stage glioma in both human and mouse tumors, as well as in relapse samples from patients. However, whether tumor-educated M2 TAMs can actively contribute to the emergence and growth of relapse is currently debated. METHODS: To investigate whether tumor-educated stromal cells remaining in the brain after surgical removal of the primary tumor can be long-lived and retain their tumor-supporting function, we developed a transplantation mouse model and performed lineage-tracing. RESULTS: We discovered that macrophages can survive transplantation and stay present in the tumor much longer than previously suggested, while sustaining an M2 polarized pro-tumorigenic phenotype. Transplanted tumors showed a more aggressive growth and faster polarization of the TAMs toward an M2 phenotype compared to primary tumors, a process dependent on the presence of few co-transplanted macrophages. CONCLUSIONS: Overall, we propose a new way for tumor-educated TAMs to contribute to glioma aggressiveness by long survival and stable pro-tumorigenic features. These properties could have a relapse-supporting effect

Dynamic stroma reorganization drives blood vessel dysmorphia during glioma growth

Glioma growth and progression are characterized by abundant development of blood vessels that are highly aberrant and poorly functional, with detrimental consequences for drug delivery efficacy. The mechanisms driving this vessel dysmorphia during tumor progression are poorly understood. Using longitudinal intravital imaging in a mouse glioma model, we identify that dynamic sprouting and functional morphogenesis of a highly branched vessel network characterize the initial tumor growth, dramatically changing to vessel expansion, leakage, and loss of branching complexity in the later stages. This vascular phenotype transition was accompanied by recruitment of predominantly pro-inflammatory M1-like macrophages in the early stages, followed by in situ repolarization to M2-like macrophages, which produced VEGF-A and relocate to perivascular areas. A similar enrichment and perivascular accumulation of M2 versus M1 macrophages correlated with vessel dilation and malignancy in human glioma samples of different WHO malignancy grade. Targeting macrophages using anti-CSF1 treatment restored normal blood vessel patterning and function. Combination treatment with chemotherapy showed survival benefit, suggesting that targeting macrophages as the key driver of blood vessel dysmorphia in glioma progression presents opportunities to improve efficacy of chemotherapeutic agents. We propose that vessel dysfunction is not simply a general feature of tumor vessel formation, but rather an emergent property resulting from a dynamic and functional reorganization of the tumor stroma and its angiogenic influences

The APOSTEL recommendations for reporting quantitative optical coherence tomography studies

OBJECTIVE: To develop consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results. METHODS: A panel of experienced OCT researchers (including 11 neurologists, 2 ophthalmologists, and 2 neuroscientists) discussed requirements for performing and reporting quantitative analyses of retinal morphology and developed a list of initial recommendations based on experience and previous studies. The list of recommendations was subsequently revised during several meetings of the coordinating group. RESULTS: We provide a 9-point checklist encompassing aspects deemed relevant when reporting quantitative OCT studies. The areas covered are study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition data analysis, recommended nomenclature, and statistical analysis. CONCLUSIONS: The Advised Protocol for OCT Study Terminology and Elements recommendations include core items to standardize and improve quality of reporting in quantitative OCT studies. The recommendations will make reporting of quantitative OCT studies more consistent and in line with existing standards for reporting research in other biomedical areas. The recommendations originated from expert consensus and thus represent Class IV evidence. They will need to be regularly adjusted according to new insights and practices

Influence of Diporeia Density on Diet Composition, Relative Abundance, and Energy Density of Planktivorous Fishes in Southeast Lake Michigan

The benthic amphipod Diporeia spp. is an important prey for many fish in offshore areas of the Great Lakes, but its abundance has been rapidly decreasing. To assess the influence of Diporeia availability on the food habits, relative abundance, and energetics of planktivorous fish, the diet composition, catch per unit effort (CPUE), and energy density of plantkivorous fish in southeast Lake Michigan during 2000–2001 were compared among locations with different Diporeia densities. Diporeia densities at St. Joseph, Michigan, were near 0/m2 over much of the bottom but averaged more than 3,800/m2 at Muskegon and Little Sable Point, Michigan. Consistent with these differences in Diporeia density, fish diet composition, CPUE, and energy density varied spatially. For example, alternative prey types comprised a larger fraction of the diets of bloater Coregonus hoyi, large (>100 mm total length) alewife Alosa pseudoharengus, and slimy sculpin Cottus cognatus at St. Joseph than at Muskegon and Little Sable Point. This pattern was seasonally dependent for alewives and bloaters because Diporeia were eaten mainly in June. Food biomass per stomach was not lower at St. Joseph than elsewhere, suggesting that the spatial variation in diet composition was due to greater consumption of alternative prey by fish at St. Joseph. Although slimy sculpin and bloaters were able to feed on alternative prey, the CPUE of these species at certain depths was considerably lower at St. Joseph than at Muskegon or Little Sable Point, indicating that Diporeia availability may also influence fish abundance and distribution. Finally, a link between Diporeia density and fish energetics was suggested by the comparatively low energy density of deepwater sculpin Myoxocephalus thompsonii and large alewives at St. Joseph, a result that may reflect the low energy content of other prey relative to Diporeia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141042/1/tafs0588.pd

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study.

BACKGROUNG: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. OBJECTIVE: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. METHODS: In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. RESULTS: There was a significant increase in INL volume in eyes with new MSON during the study (N = 61/1562, β = 0.01 mm(3), p < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005, p = .025). INL volume was independent of disease progression (β = 0.002 mm(3), p = .474). CONCLUSION: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials