Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/− Mouse, a Model of Cornelia de Lange Syndrome

Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75–80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only ∼30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl+/− mice and in individuals with CdLS

Predicting source populations of vagrants using breeding population data: a case study of the lesser black-backed gull (Larus fuscus)

Vagrancy is critical in facilitating range expansion and colonization through exploration and occupation of potentially suitable habitat. Uncovering origins of vagrants will help us better understand not only species-specific vagrant movements, but how the dynamics of a naturally growing population influence vagrancy, and potentially lead to range expansion. Under the premise that occurrence of vagrants is linked to increasing population growth in the core of the breeding range, we assessed the utility of breeding population survey data to predict source populations of vagrants. Lesser Black-backed Gulls (LBBG) (Larus fuscus) served as our focal species due to their dramatic and well-documented history of vagrancy to North America in the last 30 years. We related annual occurrence of vagrants to indices of breeding population size and growth rate of breeding populations. We propose that the fastest growing population is the most likely source of recent vagrants to North America. Our study shows that it is possible to predict potential source populations of vagrants with breeding population data, but breeding surveys require increased standardization across years to improve models. For the Lesser Black-backed Gull, Iceland’s breeding population likely influenced vagrancy during the early years of colonization, but the major increase in vagrants occurred during a period of growth of Greenland’s population, suggesting that Greenland is the source population of the most recent pulse of vagrant LBBG to North America

Racial variation in the O-acetylation phenotype of human colonic mucosa

O-acetylated and non-O-acetylated sialoglycoproteins can be distinguished by the mPAS (mild periodic acid-Schiff) histochemical technique. Individual adults show one of three different patterns of staining of large intestinal mucosa: uniformly mPAS-positive, uniformly mPAS-negative, or mPAS-negative with scattered mPAS-positive crypts. To test our hypothesis that these variations are the result of a single autosomal gene (oat) polymorphism, we have studied the frequency of the three patterns of staining in a total of 435 adult colon specimens from six geographically separate populations: British, South African blacks, Icelanders, Japanese, Hong Kong Chinese, and Bahrainis. The distribution of the three types of staining fell into two groups. In Japanese and Chinese, uniformly mPAS-positive cases were much more frequent than uniformly mPAS-negative cases; this distribution differed significantly (χ 2 P<0.001) from that in non-Sine-Japanese, where the uniformly mPAS-positive phenotype was much less frequently found than the uniformly mPAS-negative phenotype. In neither of the groups did the frequency of the three phenotypes differ significantly from that predicted for a single gene polymorphism by the Hardy-Weinberg law. The variation in staining patterns between populations is consistent with variation in frequency of a single polymorphic autosomal gene (oat) controlling O-acetylation of sialic acid, probably by an O-acetyl transferase enzyme. Loss of function mutation in the high acetylator gene (oat a) in a colonic crypt stem cell in heterozygous individuals would account for the scattered discordant crypts. Gene frequencies for a variety of enzymes differ between the Sine-Japanese and non-Sine-Japanese races. This newly described gene polymorphism may be related to differential susceptibility to organisms binding specifically to either O-acetylated or non-O-acetylated sialoglycoproteins, or to differential enteric colonization by bacterial flora that vary in their relative secretion of sialidases and sialate O-acetyl esterases.link_to_subscribed_fulltex

Data from: Ecological forensics: Using single point stable isotope values to infer seasonal schedules of animals after two diet switches

Data package contains two datasets d13C data of Sanderlings from the Arctic breeding area, d13C data of prey from the staging area and d13C values of prey from the Wadden Sea. d13C values of plasma and red blood cells of Sanderlings caught in the Wadden Sea

Human Life History Evolution Explains Dissociation between the Timing of Tooth Eruption and Peak Rates of Root Growth

We explored the relationship between growth in tooth root length and the modern human extended period of childhood. Tooth roots provide support to counter chewing forces and so it is advantageous to grow roots quickly to allow teeth to erupt into function as early as possible. Growth in tooth root length occurs with a characteristic spurt or peak in rate sometime between tooth crown completion and root apex closure. Here we show that in Pan troglodytes the peak in root growth rate coincides with the period of time teeth are erupting into function. However, the timing of peak root velocity in modern humans occurs earlier than expected and coincides better with estimates for tooth eruption times in Homo erectus. With more time to grow longer roots prior to eruption and smaller teeth that now require less support at the time they come into function, the root growth spurt no longer confers any advantage in modern humans. We suggest that a prolonged life history schedule eventually neutralised this adaptation some time after the appearance of Homo erectus. The root spurt persists in modern humans as an intrinsic marker event that shows selection operated, not primarily on tooth tissue growth, but on the process of tooth eruption. This demonstrates the overarching influence of life history evolution on several aspects of dental development. These new insights into tooth root growth now provide an additional line of enquiry that may contribute to future studies of more recent life history and dietary adaptations within the genus Homo