Sensitivity of deformation twinning to grain size in titanium and magnesium

The impact of grain size on deformation twinning in commercial purity titanium and magnesium alloy Mg–3Al–1Zn (AZ31) is investigated. Tensile tests were carried out for the titanium samples; compression testing was employed for the magnesium specimens. Average values of the true twin length, true twin thickness and the number density of twins were determined using stereology. A key difference between these two materials is that twinning contributes little to the plastic strain in the titanium while it accounts for nearly all of the early plastic strain in the magnesium. In some respects (e.g. volume fraction and number density) the phenomenology of twinning differed between the two materials, while in others (e.g. twin shape and size) both materials showed a similar response. It is found that in both materials, twins span the entirety of their parent grains only for grain sizes less than ∼30 μm. Both the nucleation density per unit of nucleating interface (i.e. grain and twin boundaries) and the aspect ratio of twins scale with applied stress. The impact of grain size on twin volume fraction is modelled analytically.

Estimating nephron number in the developing kidney using the physical disector/fractionator combination

Over the last decade the development of new molecular biology tools, advanced microscopy, live imaging and systems biology approaches have revolutionized our conception of how embryonic development proceeds. One fundamental aspect of development biology is the concept of morphogenesis: understanding how a group of multipotent cells organize and differentiate into a complex organ. In Kidney Development: Methods and Protocols, expert researchers in the field detail different approaches to tackle kidney development. These approaches include culture and live imaging aspects of kidney development, analyzing the 3-dimensional aspects of branching morphogenesis as well as nephrogenesis, manipulation of the gene/protein expression during kidney development as well as in the adult kidney, and how to assess kidney malformation and disease. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Kidney Development: Methods and Protocols seeks to aid scientists in the further study of the process of morphogenesis which is fundamental important not only for studying developmental biology but also for regenerative medicine.

Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race

Background. We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation. Methods. Kidneys without overt renal disease were collected at autopsy in Mississippi, USA. The extremes of female Nglom were used to define high and low N glom for both sexes. Nglom and IGV were estimated by design-based stereology. A total of 24 African and Caucasian American females (n = 12 per race; 6 per Nglom extreme) were included. These subjects were subsequently matched to 24 comparable males by age and Nglom and to 18 additional males by age, Nglom and BSA. Results. IGV average and variance were very similar in female African and Caucasian Americans with high and low Nglom. Males with low Nglom from both races showed greater IGV average and variance than comparable females matched by age and Nglom. These differences in IGV between sexes were not observed in Caucasian Americans with low Nglom that were matched by age, Nglom and BSA. In contrast, glomeruli from African Americans were larger than those from Caucasian Americans, especially in subjects with high Nglom. Conclusions. While female Americans with low Nglom did not show glomerular hypertrophy, comparable males with low Nglom showed marked glomerular hypertrophy that was closely associated with high BSA. Glomerular size in African Americans may be confounded by multiple additional factors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring

Background: Animal studies report a nephron deficit in offspring exposed to maternal diabetes, yet are limited to models of severe hyperglycaemia which do not reflect the typical clinical condition and which are associated with foetal growth restriction that may confound nephron endowment. We aimed to assess renal morphology and function in offspring of leptin receptor deficient mice (Leprdb/+) and hypothesized that exposure to impaired maternal glucose tolerance (IGT) would be detrimental to the developing kidney.

Methods: Nephron endowment was assessed in offspring of C57BKS/J Leprdb/+ and +/+ mice at embryonic day (E)18 and postnatal day (PN)21 using design-based stereology. Transcutaneous measurement of renal function and total glomerular volume were assessed in 6-month-old offspring. Only +/+ offspring of Leprdb/+ dams were analysed.

Results: Compared with +/+ dams, Leprdb/+ dams had a 20% and 35% decrease in glucose tolerance prior to pregnancy and at E17.5 respectively. Offspring of IGT Leprdb/+ dams had approximately 15% fewer nephrons at E18.5 and PN21 than offspring of +/+ dams. There was no difference in offspring bodyweight. Despite normal renal function, total glomerular volume was 13% greater in 6-month-old offspring of IGT Leprdb/+ dams than in +/+ offspring.

Conclusions: IGT throughout gestation resulted in a nephron deficit that was established early in renal development. Maternal IGT was associated with glomerular hypertrophy in adult offspring, likely a compensatory response to maintain normal renal function. Given the increasing prevalence of IGT, monitoring glucose from early in gestation may be important to prevent altered kidney morphology.