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Retrospective examination of banked tissue from a now defunct YFP-16 mouse colony with very high YFP expression levels (∼7 times greater than those found in our standard YFP-16 colony) revealed more severe morphological abnormalities, suggesting a dose-dependent effect (Figure 3).

With progression, more severe morphological changes, such as anulus tears, disc prolapse and end-plate damage, are seen, with the formation of osteophytes [ 27].

Finally, there were significantly more severe morphological lesions (STVA or TVA) in patients of the historical cohort than in patients of the recent one (p<0.0001).

Therefore, the H3K37A mutation probably affects chromatin binding by multiple HMG proteins during conditions of reduced TORC1 activity to cause these more severe morphological effects.

This is distinct from the 'HIV enteropathy' used by some authorities to refer to a clinical condition seen in advanced HIV where no causative pathogen is readily identified, characterised by persistent diarrhoea, more severe morphological changes and marked malabsorption.

Consistent with fln1 mutants having a more severe morphological phenotype, cells of fln1-1 wextremelymely vacuolated and contained chloroplasts with more extreme defects than those of fln2 cells.

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In fact, co-incubation of TCBZ or TCBZ.SO with methimazole (MTZ), a flavin monooxygenase (FMO) enzymatic system inhibitor, lead to more severe surface morphological changes in TCBZ-resistant F. hepatica, compared to that observed after incubation with TCBZ or TCBZ.SO alone [ 15].

Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors.

Therefore, commonly reported increases in KAM may only occur in more severe cases, due to morphological changes in the pathological joint [9].

The continuous exposure of living polyps to sub-lethal doses of QDs caused time and dose dependent morphological damages more severe than Cd2+ ions at the same concentrations, impaired both reproductive and regenerative capability, activated biochemical and molecular responses.

Nutritional deficiencies and morphological lesions were more severe in the historical cohort.

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