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Adhesion between cells and other cells (cell–cell adhesion) or other tissue components (cell–matrix adhesion) is an intrinsically non-local phenomenon. Consequently, a number of recently developed mathematical models for cell adhesion have taken the form of non-local partial differential equations, where the non-local term arises inside a spatial derivative. The mathematical properties of such a non-local gradient term are not yet well understood. Here we use sophisticated estimation techniques to show local and global existence of classical solutions for such examples of adhesion-type models, and we provide a uniform upper bound for the solutions. Further, we discuss the significance of these results to applications in cell sorting and in cancer invasion and support the theoretical results through numerical simulations.
Maternal diet-induced obesity can cause detrimental developmental origins of health and disease in offspring. Perinatal exposure to a high-fat diet (HFD) can lead to later behavioral and metabolic disturbances, but it is not clear which behaviors and metabolic parameters are most vulnerable. To address this critical gap, biparental and monogamous oldfield mice (Peromyscus polionotus), which may better replicate most human societies, were used in the current study. About 2 weeks before breeding, adult females were placed on a control or HFD and maintained on the diets throughout gestation and lactation. F1 offspring were placed at weaning (30 days of age) on the control diet and spatial learning and memory, anxiety, exploratory, voluntary physical activity, and metabolic parameters were tested when they reached adulthood (90 days of age). Surprisingly, maternal HFD caused decreased latency in initial and reverse Barnes maze trials in male, but not female, offspring. Both male and female HFD-fed offspring showed increased anxiogenic behaviors, but decreased exploratory and voluntary physical activity. Moreover, HFD offspring demonstrated lower resting energy expenditure (EE) compared with controls. Accordingly, HFD offspring weighed more at adulthood than those from control fed dams, likely the result of reduced physical activity and EE. Current findings indicate a maternal HFD may increase obesity susceptibility in offspring due to prenatal programming resulting in reduced physical activity and EE later in life. Further work is needed to determine the underpinning neural and metabolic mechanisms by which a maternal HFD adversely affects neurobehavioral and metabolic pathways in offspring.
The fronting of back vowels before the segment represented by the rune
algwiz in Old Norse (Runic: kūR
ON: kýr‘cows’) is problematic
because there is no consensus on the phonetic value to be reconstructed for the
conditioner, a reflex of Proto-Germanic+/z/. This study presents an
acoustic experiment testing the fronting effect of codas [z], [ʒ],
and [ɹ] on realizations of the representative back vowel /u/, as
these are possible reconstructed values of algwiz. Based on
observed coarticulation, we argue that a voiced alveolar fricative
[z]—and not postalveolar [ʒ] or rhotic
[ɹ]—is the best reconstruction for the conditioner of
R-umlaut, and that this reflex of PGmc+/z/ in North Germaniccaused
umlaut before rhotacism and merger with PGmc+/r/.
Poor nutrition during fetal development can permanently alter growth, cardiovascular physiology and metabolic function. Animal studies have shown that prenatal undernutrition followed by balanced postnatal nutrition alters deoxyribonucleic acid (DNA) methylation of gene promoter regions of candidate metabolic control genes in the liver. The aim of this study was to investigate whether methylation status of the proximal promoter regions of four candidate genes differed between individuals exposed to the Dutch famine in utero. In addition, we determined whether methylation status of these genes was associated with markers of metabolic and cardiovascular disease and adult lifestyle. Methylation status of the GR1-C (glucocorticoid receptor), PPARγ (peroxisome proliferator-activated receptor gamma), lipoprotein lipase and phosphatidylinositol 3 kinase p85 proximal promoters was investigated in DNA isolated from peripheral blood samples of 759 58-year-old subjects born around the time of the 1944–45 Dutch famine. We observed no differences in methylation levels of the promoters between exposed and unexposed men and women. Methylation status of PPARγ was associated with levels of high-density lipoprotein cholesterol and triglycerides as well as with exercise and smoking. Hypomethylation of the GR promoter was associated with adverse adult lifestyle factors, including higher body mass index, less exercise and more smoking. The previously reported increased risk of cardiovascular and metabolic disease after prenatal famine exposure was not associated with differences in methylation status across the promoter regions of these candidate genes measured in peripheral blood. The adult environment seems to affect GR and PPARγ promoter methylation.
Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ß receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.
Evidence from previous studies suggests an association between prenatal exposure to famine and increased risk for depression. The aim of this study was to investigate whether prenatal exposure to the Dutch famine is associated with self-reported depression/anxiety and whether a potential association is mediated by the presence of cardio-metabolic disease. A total of 819 persons, born as term singletons around the 1944–1945 Dutch famine, filled out the Hospital Anxiety and Depression Scale (HADS) and were asked about their medical history. As indicators of cardio-metabolic disease we included type 2 diabetes (T2D), hypertension and coronary heart disease (CHD). In the total study population, exposure to famine during early gestation was associated with the presence of self-reported mild-to-severe anxiety. Evidence was found for several interactions between exposure in early gestation and sex. Subsequent analyses according to sex showed that men exposed to famine during early gestation scored higher on the HADS depression scale. Self-reported mild-to-severe anxiety symptoms were more prevalent among early exposed men. No such differences were found in women. T2D and hypertension were not correlated with any of the depression and anxiety measures. Adjusting for the presence of CHD did minimally attenuate the size of the reported associations. In conclusion, the present results do not match those previously reported in prenatally famine-exposed individuals. We found only weak evidence for an association between prenatal famine exposure and symptoms of depression and anxiety, which was shown exclusively in men exposed during early gestation.
Early Intervention in Psychosis Services (EIS) for young people in England experiencing first-episode psychosis (FEP) were commissioned in 2002, based on an expected incidence of 15 cases per 100 000 person-years, as reported by schizophrenia epidemiology in highly urban settings. Unconfirmed reports from EIS thereafter have suggested higher than anticipated rates. The aim of this study was to compare the observed with the expected incidence and delineate the clinical epidemiology of FEP using epidemiologically complete data from the CAMEO EIS, over a 6-year period in Cambridgeshire, for a mixed rural–urban population.
A population-based study of FEP (ICD-10, F10–39) in people aged 17–35 years referred between 2002 and 2007; the denominator was estimated from mid-year census statistics. Sociodemographic variation was explored by Poisson regression. Crude and directly standardized rates (for age, sex and ethnicity) were compared with pre-EIS rates from two major epidemiological FEP studies conducted in urban English settings.
A total of 285 cases met FEP diagnoses in CAMEO, yielding a crude incidence of 50 per 100 000 person-years [95% confidence interval (CI) 44.5–56.2]. Age- and sex-adjusted rates were raised for people from black ethnic groups compared with the white British [incidence rate ratio (IRR) 2.1, 95% CI 1.1–3.8]. Rates in our EIS were comparable with pre-EIS rates observed in more urban areas after age, sex and ethnicity standardization.
Our findings suggest that the incidence observed in EIS is far higher than originally anticipated and is comparable to rates observed in more urban settings prior to the advent of EIS. Sociodemographic variation due to ethnicity and other factors extend beyond urban populations. Our results have implications for psychosis aetiology and service planning.
We discuss theoretical and experimental approaches to three distinct
developmental systems that illustrate how theory can influence experimental work
and vice-versa. The chosen systems – Drosophila melanogaster,
bacterial pattern formation, and pigmentation patterns – illustrate the
fundamental physical processes of signaling, growth and cell division, and cell
movement involved in pattern formation and development. These systems exemplify
the current state of theoretical and experimental understanding of how these
processes produce the observed patterns, and illustrate how theoretical and
experimental approaches can interact to lead to a better understanding of
development. As John Bonner said long ago `We have arrived at the stage where models are useful to suggest
experiments, and the facts of the experiments in turn lead to new and improved
models that suggest new experiments. By this rocking back and forth between the
reality of experimental facts and the dream world of hypotheses, we can move
slowly toward a satisfactory solution of the major problems of developmental
During vertebrate development cells acquire different fates depending largely on
their location in the embryo. The definition of a cell's developmental
fate relies on extensive intercellular communication that produces positional
information and ultimately generates an appropriately proportioned anatomy. Here
we place reaction-diffusion mechanisms in the context of general concepts
regarding the generation of positional information during development and then
focus on these mechanisms as parsimonious systems for positioning anatomical
structures relative to one another. In particular, we discuss the evidence for
reaction-diffusion systems operating in the developing skin to yield the
periodic arrangements of hairs and feathers and discuss how best to
bring together experimental molecular biology and numerical simulations to yield
a more complete understanding of the mechanisms of development and natural
Salmonella Newport causes more than an estimated 100 000 infections annually in the United States. In 2002, tomatoes grown and packed on the eastern shore of Virginia contaminated with a pan-susceptible S. Newport strain caused illness in 510 patients in 26 states. In July–November 2005, the same strain caused illness in at least 72 patients in 16 states. We conducted a case-control study during the 2005 outbreak, enrolling 29 cases and 140 matched neighbourhood controls. Infection was associated with eating tomatoes (matched odds ratio 9·7, 95% confidence interval 3·3–34·9). Tomatoes were traced back to the eastern shore of Virginia, where the outbreak strain was isolated from pond water used to irrigate tomato fields. Two multistate outbreaks caused by one rare strain, and identification of that strain in irrigation ponds 2 years apart, suggest persistent contamination of tomato fields. Further efforts are needed to prevent produce contamination on farms and throughout the food supply chain.
We present theoretical, computational (molecular dynamics), and experimental results describing the dynamical properties of a set of monodisperse, spherical particles confined to a two dimensional surface. An interaction model, which includes the interaction between the particles via collisions as well as the interaction with the substrate, shows that the properties of this granular system are influenced significantly by the latter. In particular, we analyze in detail the effects of slipping and rolling friction, which are usually overlooked. Theoretically, we explore the possibility of formulating a continuum, hydrodynamic-like theory applicable to this system. Further, we apply our model to the particular problem of a system of two kinds of particles with different frictional properties. Our experiments have found that friction-based segregation of particles moving on a horizontally shaken substrate can be achieved. Computational results give further insight into this novel segregation mechanism and confirm that careful and realistic modeling is needed in order to understand this effect.
Simple ionic models are applied to YBa2 Cu3 O7. It is found that additional forces are needed to constrain the barium and the planar coordinated copper atoms to be stable in their observed positions. These additional forces are compared to forces calculated from first principles. It is observed that the restoring forces are small for motion of the “in chain” oxygen atoms perpendicular to the chains.
One of the first questions likely to be asked by someone confronted for the first time by the great Oceanus plate (missorium) from Mildenhall (I, pl. VII a)** is, What was it used for? The answer is that neither it nor any of its fellow flat, decorated plates of silver, whether round or rectangular, to be surveyed in this paper, was ever used for practical, domestic purposes to serve as table-ware. It is hard to imagine the highly sophisticated and often elaborate relief- or incised-work that they carry being concealed beneath piles of fruit, vegetables, cakes, or portions of meat or fish greasy with gravy or sauce. These reliefs or engravings, whether covering the whole surface of a plate or confined to its central medallion or to its central medallion and flange, were essentially pictures for display in their owners' houses, or in temples or churches, probably mounted on brackets or shelves fixed to walls or to cupboards or chests (some are pierced by one or more holes as though for suspension on a wall), where they could be studied and admired for their beauty as works of art and/or their political, cultic or mythological implications.