Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene

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Global diversity of dipteran families (Insecta Diptera) in freshwater (excluding Simulidae, Culicidae, Chironomidae, Tipulidae and Tabanidae)

Today’s knowledge of worldwide species diversity of 19 families of aquatic Diptera in Continental Waters is presented. Nevertheless, we have to face for certain in most groups a restricted knowledge about distribution, ecology and systematic, particularly in the tropical environments. At the same time we realize a dramatically decline or even lack of specialists being able, having the time or the opportunity to extend or even secure the present information. The respective families with approximate numbers of aquatic species are: Blephariceridae (308), Deuterophlebiidae (14), Nyphomyiidae (7), Psychodidae (∼2.000), Scatopsidae (∼5), Tanyderidae (41), Ptychopteridae (69), Dixidae (173), Corethrellidae (97), Chaoboridae (∼50), Thaumaleidae (∼170), Ceratopogonidae (∼6.000), Stratiomyidae (∼43), Empididae (∼660), Lonchopteridae (2), Syrphidae (∼1.080), Sciomyzidae (∼190), Ephydridae (∼1.500), Muscidae (∼870). Numbers of aquatic species will surely increase with increased ecological and taxonomical efforts. Guest editors: E. V. Balian, C. Lévêque, H. Segers & K. Martens Freshwater Animal Diversity Assessment     

Sarcoglycan Complex: IMPLICATIONS FOR METABOLIC DEFECTS IN MUSCULAR DYSTROPHIES*

The sarcoglycans are known as an integral subcomplex of the dystrophin glycoprotein complex, the function of which is best characterized in skeletal muscle in relation to muscular dystrophies. Here we demonstrate that the white adipocytes, which share a common precursor with the myocytes, express a cell-specific sarcoglycan complex containing β-, δ-, and ϵ-sarcoglycan. In addition, the adipose sarcoglycan complex associates with sarcospan and laminin binding dystroglycan. Using multiple sarcoglycan null mouse models, we show that loss of α-sarcoglycan has no consequence on the expression of the adipocyte sarcoglycan complex. However, loss of β- or δ-sarcoglycan leads to a concomitant loss of the sarcoglycan complex as well as sarcospan and a dramatic reduction in dystroglycan in adipocytes. We further demonstrate that β-sarcoglycan null mice, which lack the sarcoglycan complex in adipose tissue and skeletal muscle, are glucose-intolerant and exhibit whole body insulin resistance specifically due to impaired insulin-stimulated glucose uptake in skeletal muscles. Thus, our data demonstrate a novel function of the sarcoglycan complex in whole body glucose homeostasis and skeletal muscle metabolism, suggesting that the impairment of the skeletal muscle metabolism influences the pathogenesis of muscular dystrophy.Muscle fat infiltration is recognized as a hallmark pathological feature in dystrophin glycoprotein complex (DGC)³-related muscular dystrophies (1) that include dystrophinopathies (2, 3) and sarcoglycanopathies (LGMD2C-F) (4). In agreement, magnetic resonance imaging measurements of fat infiltration allow accurate assessments of disease severity in Duchenne muscular dystrophy patients (3). Association of adipose tissue development with degenerative/regenerative or atrophic changes in skeletal muscle is also supported by the finding that adipogenesis-competent cells within the skeletal muscle are activated during muscle regeneration (5). However, the molecular mechanism(s) underlying muscle fatty metamorphosis remain unclear.Ectopic fat deposition in skeletal muscles is primarily described in animals and humans with lipodystrophy and sarcopenia. In these conditions, the accumulation of lipids and adipocytes in skeletal muscle is often accompanied by hyperglycemia and insulin resistance (6–11), both of which are strong indicators of muscle metabolic defects (12, 13) and deregulated adipogenesis (14). Furthermore, both adipose-derived and muscle-derived stem cells differentiate into adipocytes upon exposure to high levels of glucose (15), linking impaired muscle metabolism with muscle fat deposition.It is long held that the biogenesis of a basement membrane takes place in the earliest steps of adipogenesis and that extensive extracellular matrix (ECM) remodeling occurs throughout adipogenesis (16, 17). The concept that cell surface receptors play a role in the regulation of adipogenesis and thus may underlie metabolic disorders just recently emerged with a study of the integrin complexes (18). Given that the DGC in its capacity as an ECM receptor is critical for muscle integrity (19, 20) and that white adipocytes and skeletal muscle cells originate from the same mesenchymal precursor cells (21, 22), we set out to determine whether components of the skeletal muscle DGC are expressed in white adipocytes. Herein, we describe a unique adipose sarcoglycan (SG) complex that includes β-, δ-, and ϵ-SG. This complex is tightly associated with sarcospan (Sspn) and dystroglycan (DG). Moreover, we show that DG functions as a novel ECM receptor in white adipocytes. Because adipose tissue and skeletal muscle play critical roles in the maintenance of normal glucose homeostasis and whole body insulin sensitivity (23), we examined the metabolic consequences of the SG complex disruption in both adipose tissue and skeletal muscle. Using in vivo approaches, we observed that the β-SG null mouse (24), a mouse model of muscular dystrophy, is glucose-intolerant and exhibits whole body insulin resistance specifically due to impaired insulin-stimulated glucose uptake in skeletal muscle.     

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

Background

Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.

Methods

Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.

Results

In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate?<?0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDR_GSEA <?0.001).

Conclusion

We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.

Trial registration

ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).

     

Interactive Local Super-Resolution Reconstruction of Whole-Body MRI Mouse Data: A Pilot Study with Applications to Bone and Kidney Metastases

In small animal imaging studies, when the locations of the micro-structures of interest are unknown a priori, there is a simultaneous need for full-body coverage and high resolution. In MRI, additional requirements to image contrast and acquisition time will often make it impossible to acquire such images directly. Recently, a resolution enhancing post-processing technique called super-resolution reconstruction (SRR) has been demonstrated to improve visualization and localization of micro-structures in small animal MRI by combining multiple low-resolution acquisitions. However, when the field-of-view is large relative to the desired voxel size, solving the SRR problem becomes very expensive, in terms of both memory requirements and computation time. In this paper we introduce a novel local approach to SRR that aims to overcome the computational problems and allow researchers to efficiently explore both global and local characteristics in whole-body small animal MRI. The method integrates state-of-the-art image processing techniques from the areas of articulated atlas-based segmentation, planar reformation, and SRR. A proof-of-concept is provided with two case studies involving CT, BLI, and MRI data of bone and kidney tumors in a mouse model. We show that local SRR-MRI is a computationally efficient complementary imaging modality for the precise characterization of tumor metastases, and that the method provides a feasible high-resolution alternative to conventional MRI.     

Delineating landscape-scale processes of hydrology and plant dispersal for species-rich fen conservation: the Operational Landscape Unit approach

Restoration and conservation of species-rich nature reserves requires inclusion of landscape-scale connections and transport processes such as hydrologic flows and species dispersal. These are important because they provide suitable habitat conditions and an adequate species pool. This study aimed at identifying the key hydrologic flows and plant dispersal processes affecting a landscape with species-rich fen reserves where restoration measures are carried out to set back succession. It also intended to use this information for delineating the area relevant for conservation planning on an Operational Landscape Unit map. The study was carried out for complexes of fen ponds in former turbaries in the Vechtplassen area, The Netherlands. A number of recent insights on plant dispersal were integrated with knowledge on hydrologic flows in the present approach. The results showed that groundwater discharge to ensure mesotrophic, base-rich conditions, should be enhanced by restoring the groundwater recharge areas NE of the reserves. A nearby lake with suitable water chemistry was also identified as a key source of surface water to feed the fens in dry periods. Water dispersal was identified as important within the fen reserves, whereas dispersal by daily migrating dabbling ducks, typically occurring over 2–3 km, was the most important route connecting the reserves with the surrounding landscape. The delineation of the Operational Landscape Unit for this region provides a basis for conservation and restoration that take fundamental landscape connections and transport processes into account. This unique approach simultaneously considers hydrological transport processes as well as species dispersal in the larger landscape beyond the reserves themselves and therefore leads to greater success of restoration and conservation.     

REPRODUCTIVE PHENOLOGY OF LAMINARIA SACCHARINA (L.) LAMOUR. (PHAEOPHYTA) AT THE SOUTHERN LIMIT OF ITS DISTRIBUTION IN THE NOTHWESTERN ATLANTIC OCEAN1,2

Laminaria saccharina (L) Lamour. Sporophytes were monitored monthly from October 1982 to September 1983 to investigate reproduction phenology and relationshiops to growth paatterns aaat its southern limit of distribution in the northwest Atlantic Ocean (Long Island Soundd). Plants exhibited an annual growth pattern. Growth raate, bladelehgth, maximum width, area, stiipe lehgth an wet weight swhoed the same seasonal pattern and reached maximum values between May and June. Only blade thickness continued to increase tthrooughout the ovservation period. Blade dissintegration occurred dduring August and September. Reproductive sporophytes occurred throughout the observation period; the greatest frequency of appearance occurred in October (43.8%) and June (37.8%). The blade area covered by sori ranged from 2.4% (Janaury) to 6.1% (August). Meiospore release under laboratory conditions was maximum in May and minimum in July. No meio-spores were released in August Sporulation was not correlated with meristematic growth of nitrogen content How ever, reproductive plants were generally larger and thicker throughout the sporulation period, and had a greater carbort content is spring than nonreproductive plants. Fecundity and reproductive success of female gametophytes were maximum in spring and minimum in winter. The growth of early sporophyte stages in the laboratory was greatest in early spring; however, juvenile macroscopic stages were hardly observed in the field during summer months due to warm water temperatures. “Over-summering” of gamelophytes and / or microscopic sporophytes may account for the annual cycle of Laminaria at its southern limit of distribution.     

On the relationship between vertical microdistribution and adaptations to oxygen stress in littoral Chironomidae (Diptera)

Animals that dwell at different depths in the sediment, are adapted to different respiratory environments. It is possible that animals that occur deep in the sediment have a higher hemoglobin concentration than surface-dwelling animals. To test this hypothesis, hemoglobin concentrations and weights of eight chironomid species that dwell in the littoral zone were measured. High hemoglobin concentration and weight both seemed to contribute to an ability to cope with low oxygen concentrations, and determined the vertical distribution of chironomids in the sediment. A multiple regression equation, including these factors, was derived. It may be used to predict the median depth of occurrence for species that were not included in this study. High sensitivity of small animals to oxygen stress is discussed from a theoretical point of view.Research Assistant of the Belgian National Fund for Scientific ResearchResearch Assistant of the Belgian National Fund for Scientific Research