Structural basis for L27 domain‐mediated assembly of signaling and cell polarity complexes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102252/1/emboj7600294.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102252/2/emboj7600294-sup-0001.pd

Participation of the Cell Polarity Protein PALS1 to T-Cell Receptor-Mediated NF-κB Activation

BACKGROUND: Beside their established function in shaping cell architecture, some cell polarity proteins were proposed to participate to lymphocyte migration, homing, scanning, as well as activation following antigen receptor stimulation. Although PALS1 is a central component of the cell polarity network, its expression and function in lymphocytes remains unknown. Here we investigated whether PALS1 is present in T cells and whether it contributes to T Cell-Receptor (TCR)-mediated activation. METHODOLOGY/PRINCIPAL FINDINGS: By combining RT-PCR and immunoblot assays, we found that PALS1 is constitutively expressed in human T lymphocytes as well as in Jurkat T cells. siRNA-based knockdown of PALS1 hampered TCR-induced activation and optimal proliferation of lymphocyte. We further provide evidence that PALS1 depletion selectively hindered TCR-driven activation of the transcription factor NF-κB. CONCLUSIONS: The cell polarity protein PALS1 is expressed in T lymphocytes and participates to the optimal activation of NF-κB following TCR stimulation

Sudden massive neck swelling due to hemorrhage of a thyroid adenoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Sudden swelling of the neck is an emergency situation that can be life-threatening for the patient. Therefore, an understanding of the possible underlying pathology is of great importance. Sudden massive swelling of the neck because of intralesional bleeding of a thyroid adenoma is seldom encountered but must be considered. Such massive swelling caused by spontaneous bleeding of a thyroid adenoma has not yet been described in the literature.</p> <p>Case presentation</p> <p>We report the case of a 71-year-old Caucasian man with sudden massive neck swelling due to intralesional bleeding of a thyroid adenoma. We present his clinical history, physical examination results, computed tomography (CT) scans, and histological findings after surgery. He presented with sudden massive swelling of the left side of his neck after sneezing while working with his hands over his head. An ear, nose, and throat examination showed a painless swelling of the left side of his neck and a displacement of his larynx to the right. CT scans revealed a mass originating from the left lobe of his thyroid gland and the mass displaced his larynx and trachea. A surgical exploration showed a greatly enlarged left lobe of his thyroid gland. A histopathological examination showed a hemorrhagic infarction of a follicular thyroid adenoma.</p> <p>Conclusions</p> <p>Sudden intralesional bleeding of a thyroid adenoma is a rare condition but one that should be considered in cases of sudden and massive swelling of the neck.</p

Terahertz underdamped vibrational motion governs protein-ligand binding in solution

Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein–molecule interactions, and has wider implications for biochemical reactivity and biological function

Pattern of lateral neck metastases in N0 papillary thyroid carcinoma

<p>Abstract</p> <p>Background</p> <p>Indication and extent of lateral prophylactic neck dissection (PLND) in papillary thyroid carcinoma (PTC) is very controversial.</p> <p>Methods</p> <p>We retrospectively analysed 131 patients who underwent thyroidectomy and prophylactic lateral neck dissection from level II to V for PTC.</p> <p>Results</p> <p>140 PLND were performed. The occult lymph node metastases (OLNM) overall rate was 18.6%. The incidence of node involvement was 10% at level III and 6.4% at level IIa. Level IV and level Vb were both concerned by 5.7% OLNM. Only 2.9% of level IIb contained OLNM. None of the level Va ND revealed OLNM.</p> <p>Conclusions</p> <p>OLNM from PTC occurs commonly in level IIa, III, IV and Vb. Incidence in other levels is low. For surgeons that usually perform PLND, we believe that a selective neck dissection of levels IIa, III, IV and Vb in N0 neck PTC is sufficient for the clearance of occult metastases.</p

The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure

<p>Abstract</p> <p>Background</p> <p>Spontaneous bacterial peritonitis (SBP) is a common clinical disease and one of the most severe complications of acute liver failure (ALF). Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α) on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1) protein in a mouse model of ALF.</p> <p>Methods</p> <p>We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS) or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed.</p> <p>Results</p> <p>Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ) disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1) antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression.</p> <p>Conclusion</p> <p>TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.</p

Perpendicular Magnetic Anisotropy in FePt Patterned Media Employing a CrV Seed Layer

A thin FePt film was deposited onto a CrV seed layer at 400°C and showed a high coercivity (~3,400 Oe) and high magnetization (900–1,000 emu/cm3) characteristic of L10 phase. However, the magnetic properties of patterned media fabricated from the film stack were degraded due to the Ar-ion bombardment. We employed a deposition-last process, in which FePt film deposited at room temperature underwent lift-off and post-annealing processes, to avoid the exposure of FePt to Ar plasma. A patterned medium with 100-nm nano-columns showed an out-of-plane coercivity fivefold larger than its in-plane counterpart and a remanent magnetization comparable to saturation magnetization in the out-of-plane direction, indicating a high perpendicular anisotropy. These results demonstrate the high perpendicular anisotropy in FePt patterned media using a Cr-based compound seed layer for the first time and suggest that ultra-high-density magnetic recording media can be achieved using this optimized top-down approach

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

False-negative PD-L1 immunostaining in ethanol-fixed EBUS-TBNA specimens of non-small cell lung cancer patients

Aims Programmed death-ligand 1 (PD-L1) immunostaining is used to predict which non-small-cell lung cancer (NSCLC) patients will respond best to treatment with programmed cell death protein 1/PD-L1 inhibitors. PD-L1 immunostaining is sometimes performed on alcohol-fixed cytological specimens instead of on formalin-fixed paraffin-embedded (FFPE) biopsies or resections. We studied whether ethanol prefixation of clots from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results in diminished PD-L1 immunostaining as compared with formalin fixation. Methods and results FFPE cell blocks from EBUS-TBNA specimens of 54 NSCLC patients were identified. For each case, paired samples were available, consisting of clots directly immersed in formalin and clots prefixed in Fixcyt (50% ethanol). Serial sections were immunostained for PD-L1 by use of the standardised SP263 assay and the 22C3 antibody as a laboratory-developed test (LDT). PD-L1 positivity was determined with two cut-offs (1% and 50%). Concordance of PD-L1 positivity between the formalin-fixed (gold standard) and ethanol-prefixed material was assessed. When the 22C3 LDT was used, 30% and 36% of the ethanol-prefixed specimens showed false-negative results at the 1% and 50% cut-offs, respectively (kappa 0.64 and 0.68). When SP263 was used, 22% of the ethanol-prefixed specimens showed false-negative results at the 1% cut-off (kappa 0.67). At the 50% cut-off, concordance was higher (kappa 0.91), with 12% of the ethanol-prefixed specimens showing false-negative results. Conclusion Ethanol fixation of EBUS-TBNA specimens prior to formalin fixation can result in a considerable number of false-negative PD-L1 immunostaining results when a 1% cut-off is used and immunostaining is performed with SP263 or the 22C3 LDT. The same applies to use of the 50% cut-off when immunostaining is performed with the 22C3 LDT