Bankruptcy - Debtor\u27s Exercise of the Cram Down Option - Valuation Standard for Collateral in Chapter 13

The Supreme Court of the United States held that section 506(a) of the Bankruptcy Code directs the application of the replacement value standard to collateral when a Chapter 13 debtor exercises the cram down option of section 1325(a)(5)(B) in its rehabilitation plan by retaining and using the collateral over the secured creditor\u27s objection. Associates Commercial Corp. v. Rash, 117 S. Ct. 1879 (1997)

Claudin-10 is required for relay of left–right patterning cues from Hensen’s node to the lateral plate mesoderm

AbstractSpecies-specific symmetry-breaking events at the left–right organizer (LRO) drive an evolutionarily-conserved cascade of gene expression in the lateral plate mesoderm that is required for the asymmetric positioning of organs within the body cavity. The mechanisms underlying the transfer of the left and right laterality information from the LRO to the lateral plate mesoderm are poorly understood. Here, we investigate the role of Claudin-10, a tight junction protein, in facilitating the transfer of left–right identity from the LRO to the lateral plate mesoderm. Claudin-10 is asymmetrically expressed on the right side of the chick LRO, Hensen’s node. Gain- and loss-of-function studies demonstrated that right-sided expression of Claudin-10 is essential for normal rightward heart tube looping, the first morphological asymmetry during organogenesis. Manipulation of Claudin-10 expression did not perturb asymmetric gene expression at Hensen’s node, but did disrupt asymmetric gene expression in the lateral plate mesoderm. Bilateral expression of Claudin-10 at Hensen’s node prevented expression of Nodal, Lefty-2 and Pitx2c in the left lateral plate mesoderm, while morpholino knockdown of Claudin-10 inhibited expression of Snail1 in the right lateral plate mesoderm. We also determined that amino acids that are predicted to affect ion selectivity and protein interactions that bridge Claudin-10 to the actin cytoskeleton were essential for its left–right patterning function. Collectively, our data demonstrate a novel role for Claudin-10 during the transmission of laterality information from Hensen’s node to both the left and right sides of the embryo and demonstrate that tight junctions have a critical role during the relay of left–right patterning cues from Hensen’s node to the lateral plate mesoderm

太政官日誌（自六十三至六十七、南部雄麿へノ御沙汰書外）

During neural tube closure, regulated changes at the level of individual cells are translated into large-scale morphogenetic movements to facilitate conversion of the flat neural plate into a closed tube. Throughout this process, the integrity of the neural epithelium is maintained via cell interactions through intercellular junctions, including apical tight junctions. Members of the claudin family of tight junction proteins regulate paracellular permeability, apical-basal cell polarity and link the tight junction to the actin cytoskeleton. Here, we show that claudins are essential for neural tube closure: the simultaneous removal of Cldn3, -4 and -8 from tight junctions caused folate-resistant open neural tube defects. Their removal did not affect cell type differentiation, neural ectoderm patterning nor overall apical-basal polarity. However, apical accumulation of Vangl2, RhoA, and pMLC were reduced, and Par3 and Cdc42 were mislocalized at the apical cell surface. Our data showed that claudins act upstream of planar cell polarity and RhoA/ROCK signaling to regulate cell intercalation and actin-myosin contraction, which are required for convergent extension and apical constriction during neural tube closure, respectively

Characterization of Claudin-dependent morphogenetic events during neural tube closure and the impact of CLDN variants

The claudin family of tight junction proteins regulates paracellular permeability, apical-basal cell polarity, and cell adhesion and their cytoplasmic C-termini interact with the actin cytoskeleton. Through these activities, claudins have the potential to coordinate cell and tissue behaviors during epithelial morphogenesis. We previously showed that a subset of claudins is differentially expressed between the neural and non-neural epithelium during neural tube closure. This led to my hypothesis that these domains of claudin expression correlate to claudin function during neural tube morphogenesis and, if true, I predicted that deleterious missense mutations in CLDN genes would contribute to increased susceptibility to human neural tube defects (NTDs). I showed that selective removal of two of the eleven claudins expressed in the neural ectoderm of chick embryos, Cldn4 and -8, caused open NTDs due to defective convergent extension and failure of apical constriction at the neural plate midline. The failure of these morphogenetic events appears to be due to aberrant protein localization to the apical surface. In contrast, removing only Cldn3 from the non-neural ectoderm affected the epithelial remodeling events required for fusion of the dorsal tips of the neural folds to form the closed neural tube and continuous overlying layer of non-neural ectoderm. Claudin-depleted mouse embryos also exhibited NTDs. Sequence analysis of 125 patients with open spinal NTDs identified nine rare and five novel missense variants in nine CLDN genes. Functional validation studies revealed that overexpression of CLDN19 I22T and E209G, but not wild-type CLDN19, caused open NTDs in chick embryos due to defects in neural fold fusion and convergent extension, respectively. My data indicate that claudins play an evolutionary conserved role in vertebrate neural tube closure and that deleterious missense mutations in CLDN genes may contribute to human NTDs by impeding critical phases of neural tube closure. Furthermore, my data indicate that the combination of claudins expressed in an epithelial cell layer creates distinct compartments that regulate intracellular signaling events at the apical surface of epithelial cells to influence epithelial morphogenesis.Les claudines sont des composantes intégrales des jonctions serrées et qui régulent la perméabilité paracellulaire, la polarité cellulaire apicale-basale, et l'adhésion cellulaire. De plus, le domaine C-terminale des claudines se lie au cytosquelette d'actine. Par l'entremise de ces activités, les claudines ont le potentiel de coordonner les comportements des cellules et des tissus pendant la morphogenèse épithéliale. Précédemment, nous avons démontré que l'expression des membres de la famille des claudines est différente dans le neuroépithélium comparé à l'épithélium non-neural pendant la fermeture du tube neural. Cette observation nous a mené à formuler l`hypothèse suivante: les patrons d'expression des claudines dans l'épithélium correspondent aux fonctions des claudines pendant la formation du tube neural. Si tel est le cas, des mutations pathogéniques dans les CLDN contribueraient aux facteurs génétiques augmentent le risque d'anomalies de fermeture du tube neural. Nous avons démontré que la suppression sélective de deux des onze claudines exprimées dans les cellules neuroectodermiques de l'embryon de poulet cause des anomalies de fermeture du tube neural dues aux défauts de l'extension convergente et à la constriction apicale des cellules au centre de la plaque neurale. L'échec de mouvements morphogéniques semble être causé par la relocalisation des protéines à la surface apicale. La suppression de Cldn3 dans les cellules non-neuroectodermiques cause des anomalies de fermeture du tube neural dues au fait que les plis neuraux, ainsi que l`ectoderme non-neurale, ne fusionnent pas. La suppression de certaines claudines dans les embryons de souris cause un défaut de fermeture du tube neural. Le séquençage de 125 patients avec des anomalies de fermeture du tube neural à l'extrémité caudale a identifié neuf changements nucléiques rares et cinq changements non-rapportés dans neuf CLDN. Les études fonctionnelles ont montré que la surexpression du changement protéique I22T et E209G dans CLDN19, mais pas dans CLDN19 sauvage, ne permettait pas la fermeture du tube neural dans les embryons de poulet. Ceci est dû au défaut de fusionnement des plis neuraux et à l'extension convergente, respectivement. Ces résultats suggèrent que les claudines jouent un rôle essentiel dans la fermeture du tube neural chez les vertébrés et que les changements faux-sense pathogéniques dans ces gènes peuvent contribuer aux anomalies de fermeture du tube neural chez les humains en bloquant certaines phases critiques lors de la fermeture du tube neural. De plus, la combinaison de claudines exprimée par les tissus épithéliaux crée des microenvironnements qui servent à coordonner les évènements intracellulaires au niveau du pôle apical

Non-malignant Fibrosing Tumors in the Pediatric Hand: A Clinicopathologic Case Review

Non-malignant fibrosing tumors in the pediatric hand or juvenile fibromatoses are clinically challenging because of their relatively infrequent occurrence and because of the variety of names associated with these diseases. We conducted a review of a personal case series of pediatric patients with these tumors and discuss here the more common histologic types and clinical characteristics of the disease spectrum in the context of the available published literature. All histologic samples were reviewed by a single pathologist. Infantile myofibromatosis, fibrous hamartoma of infancy, juvenile aponeurotic fibromatosis, palmar fibromatosis (Dupuytren’s type), infantile digital fibromatosis (Reye’s tumor), fibroma of the tendon sheath, and melorheostosis represent the encountered lesions