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Organs are anatomically compartmentalised to cater for specialised functions. In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. While several studies indicate the critical importance of non-epithelial cells during development and homeostasis, the extent to which these cells contribute to regionalisation during morphogenesis remains unexplored. Here, we identify a mesenchymal-epithelial crosstalk that shapes the developing SI during late morphogenesis. We find that subepithelial mesenchymal cells are characterised by gradients of factors supporting Wnt signalling and stimulate epithelial growth in vitro. Such a gradient impacts epithelial gene expression and regional villus formation along the anterior-posterior axis of the SI. Notably, we further provide evidence that Wnt signalling directly regulates epithelial expression of Sonic Hedgehog (SHH), which, in turn, acts on mesenchymal cells to drive villi formation. Taken together our results uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments that is central for anterior-posterior regionalisation and correct formation of the SI. The small intestine forms via crosstalk between epithelial and mesenchymal cell compartments. Here, the authors show that a gradient of Wnt signalling along the anterior-posterior axis regulates Sonic Hedgehog which is required for correct formation and regionalization of the small intestine. [ABSTRACT FROM AUTHOR]

Understanding how diet affects reproduction and survival is a central aim in evolutionary biology. Although this relationship is likely to differ between the sexes, we lack data relating diet to male reproductive traits. One exception to this general pattern is Drosophila melanogaster, where male dietary intake was quantified using the CApillary FEeder (CAFE) method. However, CAFE feeding reduces D. melanogaster survival and reproduction, so may distort diet-fitness outcomes. Here, we use the Geometric Framework of Nutrition to create nutrient landscapes that map sex-specific relationships between protein, carbohydrate, lifespan and reproduction in D. melanogaster. Rather than creating landscapes with consumption data, we map traits onto the nutrient composition of forty agar-based diets, generating broad coverage of nutrient space. We find that male and female lifespan was maximised on low protein, high carbohydrate blends (~ 1P:15.9C). This nutrient ratio also maximised male reproductive rates, but females required more protein to maximise daily fecundity (1P:1.22C). These results are consistent with CAFE assay outcomes. However, the approach employed here improved female fitness relative to CAFE assays, while effects of agar versus CAFE feeding on male fitness traits depended on the nutrient composition of experimental diets. We suggest that informative nutrient landscapes can be made without measuring individual nutrient intake and that in many cases, this may be preferable to using the CAFE approach. The most appropriate method will depend on the question and species being studied, but the approach adopted here has the advantage of creating nutritional landscapes when dietary intake is hard to quantify. [ABSTRACT FROM AUTHOR]

The small intestine is a specialised organ, essential for nutrient digestion and absorption. It is lined with a complex epithelial cell layer. Intestinal epithelial cells can be cultured in three-dimensional (3D) scaffolds as self-organising entities with distinct domains containing stem cells and differentiated cells. Recent developments in bioengineering provide new possibilities for directing the organisation of cells in vitro. In this Perspective, focusing on the small intestine, we discuss how studies at the interface between bioengineering and intestinal biology provide new insights into organ function. Specifically, we focus on engineered biomaterials, complex 3D structures resembling the intestinal architecture, and micro-physiological systems. Maria Antfolk and Kim Jensen discuss how to model intestinal epithelial cell function in the dish and how various physiologically important environmental conditions, for example, extracellular matrix, pressure and flow, can be modelled and how this is applicable to clinical work. [ABSTRACT FROM AUTHOR]

Adult intestinal stem cells are located at the bottom of crypts of Lieberkühn, where they express markers such as LGR51,2 and fuel the constant replenishment of the intestinal epithelium1. Although fetal LGR5-expressing cells can give rise to adult intestinal stem cells3,4, it remains unclear whether this population in the patterned epithelium represents unique intestinal stem-cell precursors. Here we show, using unbiased quantitative lineage-tracing approaches, biophysical modelling and intestinal transplantation, that all cells of the mouse intestinal epithelium—irrespective of their location and pattern of LGR5 expression in the fetal gut tube—contribute actively to the adult intestinal stem cell pool. Using 3D imaging, we find that during fetal development the villus undergoes gross remodelling and fission. This brings epithelial cells from the non-proliferative villus into the proliferative intervillus region, which enables them to contribute to the adult stem-cell niche. Our results demonstrate that large-scale remodelling of the intestinal wall and cell-fate specification are closely linked. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissues following damage5–9, revealing that stem-cell identity is an induced rather than a hardwired property. Lineage tracing, biophysical modelling and intestinal transplantation approaches are used to demonstrate that, in the mouse fetal intestinal epithelium, cells are highly plastic with respect to cellular identity and, independent of LGR5 expression and cell position, can contribute to the adult stem cell compartment. [ABSTRACT FROM AUTHOR]

Maintenance of adult tissues is carried out by stem cells and is sustained throughout life in a highly ordered manner. Homeostasis within the stem-cell compartment is governed by positive- and negative-feedback regulation of instructive extrinsic and intrinsic signals. ErbB signalling is a prerequisite for maintenance of the intestinal epithelium following injury and tumour formation. As ErbB-family ligands and receptors are highly expressed within the stem-cell niche, we hypothesize that strong endogenous regulators must control the pathway in the stem-cell compartment. Here we show that Lrig1, a negative-feedback regulator of the ErbB receptor family, is highly expressed by intestinal stem cells and controls the size of the intestinal stem-cell niche by regulating the amplitude of growth-factor signalling. Intestinal stem-cell maintenance has so far been attributed to a combination of Wnt and Notch activation and Bmpr inhibition. Our findings reveal ErbB activation as a strong inductive signal for stem-cell proliferation. This has implications for our understanding of ErbB signalling in tissue development and maintenance and the progression of malignant disease. [ABSTRACT FROM AUTHOR]

The nutritional composition of prey is known to influence predator life histories, but how the life history strategies of predators affect their susceptibility to nutrient imbalance is less investigated. We used two wolf spider species with different life histories as model predators: Pardosa amentata, which have a fixed annual life cycle, and Pardosa prativaga, which reproduce later and can extend development across 2 years. We fed juvenile spiders of the two species ad libitum diets of one of six Drosophila melanogaster fly types varying in lipid:protein composition during three instars, from the start of the second instar until the fifth instar moult. We then tested for interactions between predator species and prey nutrient composition on several life history parameters. P. amentata completed the three instars faster and grew larger carapaces and heavier body masses than P. prativaga, but the two species responded differently to variation in prey lipid:protein ratio. Duration of the instars increased when feeding on protein-poor prey in P. amentata, but was unaffected by diet in P. prativaga. Likewise, the effect of diet on body composition was more pronounced in P. amentata than in P. prativaga. Prey nutrient composition thus affected the two species differently. During macronutrient imbalance P. amentata appear to prioritize high growth rates while experiencing highly variable body compositions, whereas P. prativaga maintain more constant body compositions and have slower growth. These can be seen as different consequences of a fixed annual and a plastic annual-biennial life cycle. [ABSTRACT FROM AUTHOR]

Objective: Diabetes is a common, debilitating chronic illness with multiple impacts. The impact on treatment satisfaction, productivity impairment and the symptom experience may be among the most important for patient-reported outcomes. This study developed and validated disease-specific, patient-reported measures for these outcomes that address limitations in currently available measures.Methods: Data was collected from the literature, experts and patients and a conceptual model of the patient-reported impact of diabetes was created. Item pools, based on the conceptual model, were then generated. The items were administered to 991 diabetes patients via a web-based survey to perform item reduction, identify relevant factor structures and assess reliability and validity following an a-priori analysis plan.Results: All validation criteria and hypotheses were met resulting in three new, valid measures: a 21-item Satisfaction Measure (three sub-scales: burden, efficacy and symptoms), a 30-item Symptom Measure and a 14-item Productivity Measure assessing both life and work productivity impairments.Conclusion: This triad of measures captures important components of the multifaceted diabetes patient experience and can be considered as valid, viable options when choosing measures to assess patient-reported outcomes. Addressing these outcomes may assist researchers and clinicians to develop more patient-centered diabetes interventions and care. [ABSTRACT FROM AUTHOR]

Filamentous bacteriophage offers the possibility of linking genotype with phenotype in one genetic package. By creating a library of different proteins as fusion to one of the coat proteins of filamentous bacteriophage it becomes possible to isolate proteins based on their binding characteristics. Phage displayed libraries of varying formats, ranging from small peptides to antibody fragments, have been selected successfully for ligands toward a large panel of targets. These peptides and antibody fragments are applicable in analysis of the behaviour of certain proteins with respect to changes in biological processes such as aging, thus providing valuable tools for a general understanding of the aging process. Alternatively, display of antibody fragments or peptides on filamentous bacteriophage can be instrumental in the discovery of novel antigens as exemplified by selections on cell surfaces or on complex protein mixtures such as sera from aging individuals. Although phage display has been applied successfully in a large number of studies relating to cancer, viral infections and other biological processes, its application in the field of aging research is yet to be realised. [ABSTRACT FROM AUTHOR]

Predatory arthropods are used for biological control in greenhouses, but there is increasing interest to extend their use to the outdoor environment where temperatures are typically lower. Acclimation at low temperature increases the ability of ectotherms to cope with subsequent more extreme cold, but may involve costs or benefits to other performance traits. A recent study in mesostigmatid mites (Gaeolaelaps aculeifer) showed that starvation tolerance was improved following a period of cold exposure. However, the physiological mechanisms that underlie improved starvation tolerance following cold exposure were not investigated. To examine whether cold acclimation would also improve starvation tolerance in an insect, we repeated the starvation study in another arthropod predator, the pirate bug Orius majusculus, as well as in G. aculeifer. Before tests, the two species were acclimated at 10, 15, or 20 °C for 7 (G. aculeifer) or 16 (O. majusculus) days. We then analyzed the effects of thermal exposure on body composition, consumption, and basal metabolic rate in both species. Our results confirmed that exposure to low temperature improves starvation tolerance in these arthropod predators. Body composition analyses revealed that both species had accumulated larger lipid stores during exposure to colder temperature, which at least in part can explain the larger starvation tolerance following cold exposure. In contrast, consumption and basal metabolic rate were not changed by thermal acclimation. Our study indicates that predatory arthropods exposed to cold increase their physiological robustness and ability to endure environmental challenges, including low temperature and low prey availability. [ABSTRACT FROM AUTHOR]

The processes involved in renewal of the epithelium that lines the mouse stomach remain unclear. Apart from the cells in the isthmus, several other populations located deeper in the gastric glands have been suggested to contribute to the maintenance of the gastric epithelium. Here, we reveal that Lrig1 is expressed in the basal layer of the forestomach and the lower part of glands in the corpus and pylorus. In the glandular epithelium of the stomach, Lrig1 marks a heterogeneous population comprising mainly non-proliferative cells. Yet, fate-mapping experiments using a knock-in mouse line expressing Cre specifically in Lrig1+ cells demonstrate that these cells are able to contribute to the long-term maintenance of the gastric epithelium. Moreover, when cultured in vitro, cells expressing high level of Lrig1 have much higher organoid forming potential than the corresponding cellular populations expressing lower levels of Lrig1. Taken together, these observations show that Lrig1 is expressed primarily by differentiated cells, but that these cells can be recruited to contribute to the maintenance of the gastric epithelium. This confirms previous observations that cells located in the lower segments of gastric glands can participate in tissue replenishment. [ABSTRACT FROM AUTHOR]

Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal epithelium, regulating both stem cell proliferation and differentiation along a specific secretory lineage. [ABSTRACT FROM AUTHOR]

Glucose-aversion is a heritable trait that evolved in a number of German cockroach (Blattella germanica L.) populations in response to strong selection with glucose-containing insecticide baits. However, in the absence of glucose-containing bait, glucose-averse (GA) cockroaches have lower performance than wild-type (WT) cockroaches in several fitness-determining traits. We allocated 48 caged populations initiated with homozygous GA and WT adults to four dietary treatments consisting of either pure rodent chow, rodent chow mixed to yield a content of either 20% glucose or 20% fructose, or a treatment consisting of choice between the 20% glucose- and the 20% fructose-containing food. After 6 months we found significantly higher frequency of WT individuals in populations restricted to the 20% glucose food, and after 12 months all dietary treatments contained significantly more WT individuals than expected. In accompanying experiments, we found lower survival and longer development time of GA nymphs restricted to glucose-containing food. We furthermore found evidence for assortative mating of females with males from their own genotype, with significant differences within WT cockroaches. Our study shows experimental evidence that within heterogeneous populations, WT German cockroaches will over time prevail in abundance over GA individuals, even when glucose is not a dietary component. [ABSTRACT FROM AUTHOR]

The authors discuss research on the first in vivo genome-wide RNA-interference (RNAi) screen, which was performed in mouse embryos to identify genes involved in non-melanoma skin cancer development. They reference the study "RNAi Screens in Mice Identify Physiological Regulators of Oncogenic Growth" by Slobodan Beronja published in the September 12, 2013 issue of the journal. They believe that some factors have opposing roles in cancer and normal-tissue maintenance.