We have previously shown that aPKC interacts with cell polarity proteins PAR-3 and PAR-6 and plays an indispensable role in cell polarization in the C. elegans one-cell embryo as well as in mammalian epithelial cells. Here, to clarify the molecular basis underlying this aPKC function in mammalian epithelial cells, we analyzed the localization of aPKC and PAR-3 during the cell repolarization process accompanied by wound healing of MTD1-A epithelial cells. Immunofluorescence analysis revealed that PAR-3 and aPKCλ translocate to cell-cell contact regions later than the formation of the primordial spot-like adherens junctions (AJs) containing E-cadherin and ZO-1. Comparison with three tight junction (TJ) membrane proteins, JAM,occludin and claudin-1, further indicates that aPKCλ is one of the last TJ components to be recruited. Consistently, the expression of a dominant-negative mutant of aPKCλ (aPKCλkn) in wound healing cells does not inhibit the formation of the spot-like AJs; rather, it blocks their development into belt-like AJs. These persistent spot-like AJs in aPKCλ-expressing cells contain all TJ membrane proteins and PAR-3,indicating that aPKC kinase activity is not required for their translocation to these premature junctional complexes but is indispensable for their further differentiation into belt-like AJs and TJs. Cortical bundle formation is also blocked at the intermediate step where fine actin bundles emanating from premature cortical bundles link the persistent spot-like AJs at apical tips of columnar cells. These results suggest that aPKC contributes to the establishment of epithelial cell polarity by promoting the transition of fibroblastic junctional structures into epithelia-specific asymmetric ones.
It is well established that intraepithelial T lymphocytes (IELs) are derived from conventional single-positive (SP) thymocytes, as well as unconventional double-negative (DN) thymocytes and CD103+CD8αβ recent thymic emigrants (RTEs). We show that IELs can be divided into two groups according to their dependency on sphingosine 1-phosphate (S1P) for trafficking into the intestines. CD4 or CD8αβ naive lymphocytes originating from SP thymocytes express high levels of type 1 S1P receptor (S1P1), and their preferential migration into the large intestine is regulated by S1P. In contrast, RTEs migrate exclusively into the small intestine, whereas DN thymic IEL precursors expressing either TCRαβ or TCRγδ migrate into both the small and large intestines. S1P does not play a role in the migration pathways of these unconventional thymic IEL precursors. Thus, down-regulation of S1P1 expression or disruption of the S1P gradient halted conventional CD4 or CD8αβ IEL trafficking into the intestines, but did not affect the trafficking of unconventional thymic IEL precursors. These data are the first to demonstrate that a lipid-mediated system discriminates IELs originating from conventional and unconventional thymic precursors.
Sphingosine 1-phosphate (S1P) has been proposed as a regulator of lymphocyte trafficking, but its role in mucosa-associated diseases, such as in food allergies, remains to be elucidated. To examine the role of S1P in allergic diseases in the intestine, we used a Th2 cell-mediated Ag-specific allergic diarrhea model and demonstrated that type 1 S1P receptor (S1P1) expression was preferentially associated with pathogenic CD4+ T cells for the development of allergic reactions. Consistent with this demonstration, treatment with FTY720, a modulator of the S1P1, prevented allergic diarrhea by inhibiting the migration of systemically primed pathogenic CD4+ T cells induced by oral challenge with allergen into the large intestine. In addition, FTY720 hampered mast cell infiltration into the large intestine, whereas eosinophil infiltration into the large intestine and total and allergen-specific serum IgE production were comparable between mock- and FTY720-treated groups. These results suggest that modulation of the S1P-mediated pathway to inhibit the migration of pathogenic CD4+ T cells and mast cells into the large intestine could be a novel strategy for preventing allergic diarrhea.
Assessment of muscle mass is important for evaluating muscle function and rehabilitation
outcomes. Ultrasound has recently been successfully used to estimate muscle mass in humans
by measuring muscle thickness. This study attempted to standardize procedures for
measuring femoral muscle thickness ultrasonographically, as well as quantify the
reliability and validity of ultrasound evaluations of muscle thickness compared to
measurements made by magnetic resonance imaging (MRI) in dogs. We evaluated the quadriceps
femoris (QF), biceps femoris (BF), semitendinosus (ST) and semimembranosus (SM) muscles of
10 clinically healthy Beagle dogs. Scans were taken in 5 different sections divided
equally between the greater trochanter and proximal patella. MRI was performed, followed
by T1-weighted and contrast-enhanced T1-weighted imaging. Muscle cross-sectional area
(CSA) was measured with MRI, and muscle thickness was measured with MRI and
ultrasonography. The thickness of the QF, BF and ST muscles as measured by ultrasound at
slices 1–3 (from the proximal end to the middle of the femur), 2–4 (middle of the femur)
and 2 (more proximal than the middle of the femur), respectively, was correlated with
muscle thickness and CSA as measured by MRI. These sites showed a flat interface between
muscle and transducer and were situated over belly muscle. No correlation between
measurement types was seen in SM muscle. We must confirm this assessment method for
various breeds, sizes, ages and muscle pathologies in dogs, thereby confirming that muscle
thickness as measured ultrasonographically can reflect muscle function.
A shiba inu dog with marked abdominal distension was diagnosed with cor triatriatum dexter and surgical correction was performed under extracorporeal circulation. The total duration of cardiac arrest was 11 minutes and total perfusion time was 34 minutes. The dog had an uneventful postoperative recovery. Postoperative contrast radiography of the caudal vena cava revealed normal flow into the right heart. Abdominal distension was no longer observed. Although several methods have been used to treat cor triatriatum dexter in dogs, the authors consider surgical correction under extracorporeal circulation to be a reliable approach.
Gnathostome jaws derive from the first pharyngeal arch (PA1), a complex structure constituted by Neural Crest Cells (NCCs), mesodermal, ectodermal and endodermal cells. Here, to determine the regionalized morphogenetic impact of Dlx5/6 expression, we specifically target their inactivation or overexpression to NCCs. NCC-specific Dlx5/6 inactivation (NCC∆Dlx5/6) generates severely hypomorphic lower jaws that present typical maxillary traits. Therefore, differently from Dlx5/6 null-embryos, the upper and the lower jaws of NCC∆Dlx5/6 mice present a different size. Reciprocally, forced Dlx5 expression in maxillary NCCs provokes the appearance of distinct mandibular characters in the upper jaw. We conclude that: (1) Dlx5/6 activation in NCCs invariably determines lower jaw identity; (2) the morphogenetic processes that generate functional matching jaws depend on the harmonization of Dlx5/6 expression in NCCs and in distinct ectodermal territories. The co-evolution of synergistic opposing jaws requires the coordination of distinct regulatory pathways involving the same transcription factors in distant embryonic territories.
This study clearly demonstrated that MCT activates ghrelin and increases NPY, suggesting that nutritional supplementation with MCT may be effective for the treatment of AN patients in an emaciated state.
Open patch-grafting can be performed in small-breed dogs and decreased the pulmonary pressure gradient in survivors at 3 months postoperatively. However, this technique is more invasive than balloon valvuloplasty and should be used cautiously in severely stenosed patients.
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