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Concept: Exocrine gland

123

Perspiration-based wearable biosensors facilitate continuous monitoring of individuals' health states with real-time and molecular-level insight. The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 µL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information. A wearable and miniaturized iontophoresis interface is an excellent solution to overcome this barrier. The iontophoresis process involves delivery of stimulating agonists to the sweat glands with the aid of an electrical current. The challenge remains in devising an iontophoresis interface that can extract sufficient amount of sweat for robust sensing, without electrode corrosion and burning/causing discomfort in subjects. Here, we overcame this challenge through realizing an electrochemically enhanced iontophoresis interface, integrated in a wearable sweat analysis platform. This interface can be programmed to induce sweat with various secretion profiles for real-time analysis, a capability which can be exploited to advance our knowledge of the sweat gland physiology and the secretion process. To demonstrate the clinical value of our platform, human subject studies were performed in the context of the cystic fibrosis diagnosis and preliminary investigation of the blood/sweat glucose correlation. With our platform, we detected the elevated sweat electrolyte content of cystic fibrosis patients compared with that of healthy control subjects. Furthermore, our results indicate that oral glucose consumption in the fasting state is followed by increased glucose levels in both sweat and blood. Our solution opens the possibility for a broad range of noninvasive diagnostic and general population health monitoring applications.

Concepts: Health, Electrochemistry, Cystic fibrosis, Gland, Exocrine gland, Glands, Exocrine system, Sweat gland

90

We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.

Concepts: Epithelium, Basement membrane, Basal lamina, Natural environment, Cornea, Connective tissue, Gland, Exocrine gland

55

Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer’s long latency and multifactorial etiology make evaluation of these chemicals in humans challenging.

Concepts: Cancer, Breast cancer, Organ, Mammal, Breast, Exocrine gland, Mammary gland, Mammary tumor

47

As tawny crazy ants (Nylanderia fulva) invade the southern USA, they often displace imported fire ants (Solenopsis invicta). Following exposure to S. invicta venom, N. fulva applies abdominal exocrine gland secretions to its cuticle. Bioassays reveal that these secretions detoxify S. invicta venom. Further, formic acid, from N. fulva venom, is the detoxifying agent. N. fulva exhibits this detoxification behavior after conflict with a variety of ant species; however, it expresses it most intensely after interactions with S. invicta. This behavior may have evolved in their shared South American native range. The unique capacity to detoxify a major competitor’s venom likely contributes substantially to its ability to displace S. invicta populations, making this behavior a causative agent in the ecological transformation of regional arthropod assemblages.

Concepts: Ecology, Gland, Exocrine gland, Ant, Red imported fire ant, Fire ant, Solenopsis daguerrei, Ants

40

Endocrine and exocrine pancreas tissues are both derived from the posterior foregut endoderm, however, the interdependence of these two cell types during their formation is not well understood. In this study, we generated mutant mice, in which the exocrine tissue is hypoplastic, in order to reveal a possible requirement for exocrine pancreas tissue in endocrine development and/or function. Since previous studies showed an indispensable role for Pdx1 in pancreas organogenesis, we used Elastase-Cre-mediated recombination to inactivate Pdx1 in the pancreatic exocrine lineage during embryonic stages. Along with exocrine defects, including impaired acinar cell maturation, the mutant mice exhibited substantial endocrine defects, including disturbed tip/trunk patterning of the developing ductal structure, a reduced number of Ngn3-expressing endocrine precursors, and ultimately fewer β cells. Notably, postnatal expansion of the endocrine cell content was extremely poor, and the mutant mice exhibited impaired glucose homeostasis. These findings suggest the existence of an unknown but essential factor(s) in the adjacent exocrine tissue that regulates proper formation of endocrine precursors and the expansion and function of endocrine tissues during embryonic and postnatal stages.

Concepts: Gene, Enzyme, Insulin, Pancreas, Endoderm, Exocrine gland, Exocrine pancreas, Acinus

28

OBJECTIVES:: To better understand the exocrine pancreatic function of very preterm infants. METHODS:: Pancreas-specific elastase 1 (PSE1) activity was determined in spot stool samples of 69 preterm infants of gestational age <32 weeks and birth weight <1,250 g. Assays were conducted on samples collected at 2 (N = 56), 4 (N = 46), and 6 weeks of age (N = 23). RESULTS:: PSE1 activity increased from week 2 (median [interquartile range] 84 [48-187] μg/g) to week 4 (164 [87-251 μg/g, P < 0.001) but not thereafter (169 [82-298] μg/g at week 6). The maturational increase in PSE1 activity was observed only in infants of gestational age <28 weeks (P < 0.001). At 2 weeks after birth, PSE1 levels were lower in infants of gestational age <28 weeks than in infants of gestational age ≥28 weeks (77 [43-110] vs. 165 [56-300] μg/g, P = 0.019), but this difference was less pronounced at 4 weeks (153 [77-226] vs. 230 [108-503] μg/g, P = 0.070) and had disappeared by 6 weeks (163 [76-258] vs. 175 [85-418] μg/g, P = 0.576).In infants on full enteral feeding regimens 4 weeks after birth, PSE1 levels were associated with weight gain per unit of energy intake (Rs = 0.431, P = 0.005). This measure of weight gain was lower (P = 0.040) in infants with PSE1 levels <200 μg/g (0.110 [0.081-0.139] g/kcal, N = 25) than in those with PSE1 levels ≥200 μg/g (0.139 [0.117-0.157] g/kcal, N = 15). Administration of pancreatic enzymes to infants showing PSE1 excretion levels <200 μg/g did not enhance weight gain. CONCLUSIONS:: Extremely preterm infants have limited exocrine pancreatic function during the first weeks of life, which may contribute to growth failure.

Concepts: Enzyme, Fetus, Pancreas, Obstetrics, Small intestine, Exocrine gland, Exocrine pancreas, Digestive enzyme

28

To maintain islets survival and function is critical in successful pancreatic transplantation. Pancreatic progenitors cells (PPCs) with lineage potentials, giving rise to exocrine, endocrine, and duct cells, reside in developing and adult pancreas. As tissue-specific stem cells, they can produce pancreatic tissue-specific matrix factors to promote islets survival and function. The aim of our research was to investigate the protective effect of rat pancreatic-duodenal homeobox 1 (Pdx1)(+)/nestin(+) PPCs on islets. In vitro, co-culturing islets with Pdx1(+)/nestin(+) PPCs prolonged the former survival from 7 to 14 days. Furthermore, with high glucose (300.8 mg/dl) stimuli, the yield of insulin in co-cultures was significantly higher than that in control group (single islets group). In vivo, co-transplanting islets and Pdx1(+)/nestin(+) PPCs for 3 days, the blood glucose of diabetic rat was significantly decreased to normal level and sustained for 2 weeks. Without Pdx1(+)/nestin(+) PPCs in islets transplantation, hyperglycemia was reversed at day 7 and recovered at day 15. Pathology analysis showed that islets had remnants in co-transplantation at day 21, as complete graft rejection in alone islets transplantation. Our study showed that Pdx1(+)/nestin(+) PPCs displayed the ability of preserving islets viability and function in vitro and prolonging their survival in vivo.

Concepts: Enzyme, Insulin, Diabetes mellitus, Pancreas, Blood sugar, In vivo, In vitro, Exocrine gland

28

Adhesives that are naturally produced by marine organisms are potential sources of inspiration in the search for medical adhesives. Investigations of barnacle adhesives are at an early stage but it is becoming obvious that barnacles utilize a unique adhesive system compared to other marine organisms. The current study examined the fine structure and chemistry of the glandular system that produces the adhesive of the barnacle Lepas anatifera. All components for the glue originated from large single-cell glands (70-180 μm). Staining (including immunostaining) showed that L-3,4-dihydroxyphenylalanine and phosphoserine were not present in the glue producing tissues, demonstrating that the molecular adhesion of barnacles differs from all other permanently gluing marine animals studied to date. The glandular tissue and adhesive secretion primarily consisted of slightly acidic proteins but also included some carbohydrate. Adhesive proteins were stored in cytoplasmic granules adjacent to an intracellular drainage canal (ICC); observations implicated both merocrine and apocrine mechanisms in the transport of the secretion from the cell cytoplasm to the ICC. Inside the ICC, the secretion was no longer contained within granules but was a flocculent material which became “clumped” as it traveled through the canal network. Hemocytes were not seen within the adhesive “apparatus” (comprising of the glue producing cells and drainage canals), nor was there any structural mechanism by which additions such as hemocytes could be made to the secretion. The unicellular adhesive gland in barnacles is distinct from multicellular adhesive systems observed in marine animals such as mussels and tubeworms. Because the various components are not physically separated in the apparatus, the barnacle adhesive system appears to utilize completely different and unknown mechanisms for maintaining the liquid state of the glue within the body, as well as unidentified mechanisms for the conversion of extruded glue into hard cement. J. Morphol., 2012. © 2012 Wiley Periodicals, Inc.

Concepts: Cell, Secretion, Cytoplasm, Liquid, Gland, Exocrine gland, Adhesive, Animal glue

27

Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished.

Concepts: Pituitary gland, Structure, Gland, Exocrine gland, Glands, Perspiration, Exocrine system, Sweat gland

27

BACKGROUND: Two varieties exist in the Chinese crested dog breed, namely hairless Chinese crested dogs presenting with hypotrichosis and dentition abnormalities, and the coated powderpuffs. Hairless Chinese crested dogs are obligate heterozygotes for a FOXI3 mutation, and this phenotype is classified as a form of canine ectodermal dysplasia. OBJECTIVES: We provide a detailed histological description of hair follicles and their density for the three subphenotypes (true hairless, semi-coated and powderpuffs) of Chinese crested dogs. Apocrine and exocrine glands of the skin and other tissues were compared with findings reported from dogs with X-linked ectodermal dysplasia. ANIMALS: Skin biopsies were collected from 22 Chinese crested dogs. Additionally, the glands of the skin and other tissues were examined from another two dogs available for postmortem examination. METHODS: Skin biopsies and tissues were processed, stained and evaluated in a blinded fashion. RESULTS: Hair follicular anomalies decreased with increasing number of hairs in the different phenotypes. The FOXI3 mutants had only simple primary hair follicles, whereas the nonmutant powderpuffs had compound follicles identical to other dog breeds. All Chinese crested dogs had an anagen-dominated hair cycle. Furthermore, apocrine glands in the skin and respiratory mucous glands of the mutant Chinese crested dogs were present and normal. CONCLUSIONS AND CLINICAL IMPORTANCE: We have identified striking histopathological differences between the three subphenotypes of Chinese crested dogs. We clearly demonstrated distinct differences between the canine ectodermal dysplasia in Chinese crested dogs and dogs with X-linked ectodermal dysplasia.

Concepts: Pancreas, Skin, Gland, Exocrine gland, Glands, Dog breed, Exocrine system, Chinese Crested Dog