The dynamics of inter-Sertoli (SC) tight junctions (TJ) are regulated by transforming growth factor-beta 3 (TGF-beta 3) via the p38 mitogen-activated protein (MAP) kinase signaling pathway

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Disruption of Sertoli-germ cell adhesion function in the seminiferous epithelium of the rat testis can be limited to adherens junctions without affecting the blood-testis barrier integrity: An in vivo study using an androgen suppression model

During spermatogenesis, both adherens junctions (AJ) (such as ectoplasmic specialization (ES), a testis-specific AJ type at the Sertoli cell-spermatid interface (apical ES) or Sertoli-Sertoli cell interface (basal ES) in the apical compartment and BTB, respectively) and tight junctions (TJ) undergo extensive restructuring to permit germ cells to move across the blood-testis barrier (BTB) as well as the seminiferous epithelium from the basal compartment to the luminal edge to permit fully developed spermatids (spermatozoa) to be sloughed at spermiation. However, the integrity of the BTB cannot be compromised throughout spermatogenesis so that postmeiotic germ cell-specific antigens can be sequestered from the systemic circulation at all times. We thus hypothesize that AJ disruption in the seminiferous epithelium unlike other epithelia, can occur without compromising the BTB-barrier, even though these junctions, namely TJ and basal ES, co-exist side-by-side in the BTB. Using an intratesticular androgen suppression-induced germ cell loss model, we have shown that the disruption of AJs indeed was limited to the Sertoli-germ cell interface without perturbing the BTB. The testis apparently is using a unique physiological mechanism to induce the production of both TJ- and AJ-integral membrane proteins and their associated adaptors to maintain BTB integrity yet permitting a transient loss of cell adhesion function by dissociating N-cadherin from β-catenin at the apical and basal ES. The enhanced production of TJ proteins, such as occludin and ZO-1, at the BTB site can supersede the transient loss of cadherin-catenin function at the basal ES. This thus allows germ cell depletion from the epithelium without compromising BTB integrity. It is plausible that the testis is using this novel mechanism to facilitate the movement of preleptotene and leptotene spermatocytes across the BTB at late stage VIII through early stage IX of the epithelial cycle in the rat while maintaining the BTB immunological barrier function. © 2005 Wiley-Liss, Inc.postprin

The proximal cis-acting elements Sp1, Sp3 and E2F regulate mouse mer gene transcription in sertoli cells

Mer belongs to the Tyro 3 family of receptor tyrosine kinases (RTKs). Together with Axl and Rse, the three RTKs are believed to play important functional roles in the male gonads because gene knockout male mice lacking all of these receptors are infertile. In the present study, postnatal expression of Axl and Rse in mouse testes decreased during maturation while expression of Mer increased age-dependently during testicular development. To investigate the transcriptional regulation of gene expression in the testis, a ≈ 1.5 kb fragment of the 5′ flanking sequence of Mer was isolated. The sequence lacks a typical TATA or CAAT box. 5′ RACE revealed that the putative major transcriptional start site of Mer is located at +102 bp upstream of the translation initiation site. Using transient transfections of luciferase reporter constructs driven by various lengths of the 5′ flanking sequence, the gene segment -321/+126 showed the highest transcriptional activity in a mouse Sertoli cell line (TM4). DNAase I footprinting experiments revealed four footprints within the region from -321 to -26, including three binding sites for the transcriptional factor Specificity protein 1 (Sp1) and one for an unknown transcriptional factor. Electrophoretic mobility shift assay (EMSA), supershift assay, mutation studies and cotransfection demonstrated that those Sp1 cis-acting motifs interacted either with Sp1 or Sp1/Sp3, depending on location and the nearby nucleotide sequences. An E2F binding site which down-regulates Mer transcription, as revealed by EMSA, deletion and mutation studies, was identified downstream in the proximity of the promoter. Taking all of these data together, the study has demonstrated that Sp1, Sp3, E2F and probably another unknown transcriptional factor play a critical role in regulating the proximal promoter activities of Mer.postprin

Cytokines and junction restructuring during spermatogenesis - A lesson to learn from the testis

In the mammalian testis, preleptotene and leptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier (BTB) at late stage VIII through early stage IX of the epithelial cycle during spermatogenesis, entering the adluminal compartment for further development. However, until recently the regulatory mechanisms that regulate BTB dynamics remained largely unknown. We provide a critical review regarding the significance of cytokines in regulating the 'opening' and 'closing' of the BTB. We also discuss how cytokines may be working in concert with adaptors that selectively govern the downstream signaling pathways. This process, in turn, regulates the dynamics of either Sertoli-Sertoli tight junction (TJ), Sertoli-germ cell adherens junction (AJ), or both junction types in the epithelium, thereby permitting TJ opening without compromising AJs, and vice versa. We also discuss how adaptors alter their protein-protein association with the integral membrane proteins at the cell-cell interface via changes in their phosphorylation status, thereby altering adhesion function at AJ. These findings illustrate that the testis is a novel in vivo model to study the biology of junction restructuring. Furthermore, a molecular model is presented regarding how cytokines selectively regulate TJ/AJ restructuring in the epithelium during spermatogenesis. © 2005 Elsevier Ltd. All rights reserved.postprin

Differential interactions between transforming growth factor-β3/ TβR1, TAB1, and CD2AP disrupt blood-testis barrier and sertoli-germ cell adhesion

The biochemical basis that regulates the timely and selective opening of the blood-testis barrier (BTB) to migrating preleptotene/leptotene spermatocytes at stage VIII of the epithelial cycle in adult rat testes is virtually unknown. Recent studies have shown that cytokines (e.g. transforming growth factor (TGF)-β3) may play a crucial role in this event. However, much of this information relies on the use of toxicants (e.g. CdCl 2), making it difficult to relay these findings to normal testicular physiology. Here we report that overexpression of TGF-β3 in primary Sertoli cells cultured in vitro indeed perturbed the tight junction (TJ) barrier with a concomitant decline in the production of BTB constituent proteins as follows: occludin, N-cadherin, and ZO-1. Additionally, local administration of TGF-β3 to testes in vivo was shown to reversibly perturb the BTB integrity and Sertoli-germ cell adhesion via the p38 MAPK and ERK signaling pathways. Most importantly, the simultaneous activation of p38 and ERK signaling pathways is dependent on the association of the TGF-β3-TβR1 complex with adaptors TAB1 and CD2AP because if TβR1 was associated preferentially with CD2AP, only Sertoli-germ cell adhesion was perturbed without compromising the BTB. Collectively, these data illustrate that local production of TGF-β3, and perhaps other TGF-βs and cytokines, by Sertoli and germ cells into the microenvironment at the BTB during spermatogenesis transiently perturbs the BTB and Sertoli-germ cell adhesion to facilitate germ cell migration when the activated TβRI interacts with adaptors TAB1 and CD2AP. However, TGF-β3 selectively disrupts Sertoli-germ cell adhesion in the seminiferous epithelium to facilitate germ cell migration without compromising BTB when TβRI interacts only with adaptor CD2AP. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.postprin

Induction of collagen expression during inter-sertoli Tight Junction (TJ) assembly in vitro

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Analyzing ranking data using decision tree

Ranking/preference data arises from many applications in marketing, psychology and politics. We establish a new decision tree model for the analysis of ranking data by adopting the concept of classification and regression tree [2]. We modify the existing splitting criteria, Gini and entropy, which can precisely measure the impurity of a set of ranking data. Two types of impurity measures for ranking data are introduced, namely n-wise and top-k measures. Minimal cost-complexity pruning is used to find the optimum-sized tree. In model assessment, the area under the ROC curve (AUC) is applied to evaluate the tree performance. The proposed methodology is implemented to analyze a partial ranking dataset of Inglehart's items collected in the 1993 International Social Science Programme survey. Change in importance of item values with country, age and level of education are identified.postprintThe European Conference on Machine Learning and Principles and Practice of Knowledge Discovery in Databases (ECML PKDD 2008), Antwerp, Belgium, 15-19 September 2008. In Proceedings of ECML PKDD 2008, p. 139-15

A tunable common mode inductor with an auxiliary winding network

Paper 1593Track no. 5 - Devices and ComponentsIn conventional switching converter, the parasitic capacitance between switching circuit and ground introduces common mode (CM) noise problem. A CM inductor is inserted in the power feeding paths to produce a high impedance to attenuate the CM noise. However, this parasitic capacitance and the CM inductor create low-frequency resonance near the switching frequency and its harmonics. Thus, the filtering performance is diminished. Increasing the CM inductance to shift the resonant frequency to low-frequency range is one of the methods to tackle this problem. However, this approach leads to increase the power losses (both core and winding losses) of the CM inductor reducing the efficiency of the converter. In this paper, a tunable CM inductor with a small-space auxiliary winding is proposed. The auxiliary winding can be connected to a passive network to alter the frequency response of the CM inductor without affecting the original inductance. As a result, the influence of the low-frequency resonance can be mitigated. A proof-of-concept protytpe is constructed and its performance is experimentally measured. Results show that the proposed tunable CM inductor operates as theoretically anticipated. © IEEE.published_or_final_versio

A Review of Superior Vena Cava Obstruction in Hong Kong Chinese Patients

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X-knife stereotactic radiosurgery for cerebral AVM: Queen Mary Hospital experience

Meeting Theme: Degenerative Lumbar SpineOral-Poster Presentation 1INTRODUCTION: This is a retrospective review of the effectiveness, safety, complications of LINAC based X-knife stereotactic radiosurgery for the treatment of cerebral AVM in Queen Mary Hospital, Hong Kong. METHODS: Retrospective search through medical records of a single institution. From 2003-2013, all patients who received X-knife stereotactic radiosurgery for cerebral AVM were included. Demographics, presenting symptoms, size of AVM, Spetzler-Martin grading, dosages, complications, follow-up …published_or_final_versio