Shifts of a resonance line in a dense atomic sample

We study the collective response of a dense atomic sample to light essentially exactly using classical-electrodynamics simulations. In a homogeneously broadened atomic sample there is no overt Lorentz-Lorenz local field shift of the resonance, nor a collective Lamb shift. However, addition of inhomogeneous broadening restores the usual mean-field phenomenology

Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame.

The endoplasmic reticulum (ER)-anchored hepatic cytochromes P450 (P450s) are enzymes that metabolize endo- and xenobiotics i.e. drugs, carcinogens, toxins, natural and chemical products. These agents modulate liver P450 content through increased synthesis or reduction via inactivation and/or proteolytic degradation, resulting in clinically significant drug-drug interactions. P450 proteolytic degradation occurs via ER-associated degradation (ERAD) involving either of two distinct routes: Ubiquitin (Ub)-dependent 26S proteasomal degradation (ERAD/UPD) or autophagic lysosomal degradation (ERAD/ALD). CYP3A4, the major human liver/intestinal P450, and the fast-turnover CYP2E1 species are degraded via ERAD/UPD entailing multisite protein phosphorylation and subsequent ubiquitination by gp78 and CHIP E3 Ub-ligases. We are gaining insight into the nature of the structural determinants involved in CYP3A4 and CYP2E1 molecular recognition in ERAD/UPD [i.e. K48-linked polyUb chains and linear and/or "conformational" phosphodegrons consisting either of consecutive sequences on surface loops and/or disordered regions, or structurally-assembled surface clusters of negatively charged acidic (Asp/Glu) and phosphorylated (Ser/Thr) residues, within or vicinal to which, Lys-residues are targeted for ubiquitination]. Structural inspection of select human liver P450s reveals that such linear or conformational phosphodegrons may indeed be a common P450-ERAD/UPD feature. By contrast, although many P450s such as the slow-turnover CYP2E1 species and rat liver CYP2B1 and CYP2C11 are degraded via ERAD/ALD, little is known about the mechanism of their ALD-targeting. On the basis of our current knowledge of ALD-substrate targeting, we propose a tripartite conjunction of K63-linked Ub-chains, P450 structural "LIR" motifs and selective cellular "cargo receptors" as plausible P450-ALD determinants

Exact electrodynamics versus standard optics for a slab of cold dense gas

We study light propagation through a slab of cold gas using both the standard electrodynamics of polarizable media, and massive atom-by-atom simulations of the electrodynamics. The main finding is that the predictions from the two methods may differ qualitatively when the density of the atomic sample $and the wavenumber of resonant light$k$satisfy$rho k^-3gtrsim 1$. The reason is that the standard electrodynamics is a mean-field theory, whereas for sufficiently strong light-mediated dipole-dipole interactions the atomic sample becomes correlated. The deviations from mean-field theory appear to scale with the parameter$rho k^-3$, and we demonstrate noticeable effects already at$rho k^-3 simeq 10^-2$. In dilute gases and in gases with an added inhomogeneous broadening the simulations show shifts of the resonance lines in qualitative agreement with the predicted Lorentz-Lorenz shift and "cooperative Lamb shift", but the quantitative agreement is unsatisfactory. Our interpretation is that the microscopic basis for the local-field corrections in electrodynamics is not fully understood

Two cases of female hydrocele of the canal of nuck

The processus vaginalis within the inguinal canal forms the canal of Nuck, which is a homolog of the processus vaginalis in women. Incomplete obliteration of the processus vaginalis causes indirect inguinal hernia or hydrocele of the canal of Nuck, a very rare condition in women. Here, we report 2 cases of hydrocele of the canal of Nuck that were diagnosed with ultrasonography in both cases and magnetic resonance imaging in 1 case to confirm the sonographic diagnosis. High ligation and hydrocelectomy were conducted in both patients. In 1 patient, 14 months later, the occurrence of contralateral inguinal hernia was suspected, but did not require surgery. The other patient had a history of surgery for left inguinal hernia 11 months before the occurrence of right hydrocele of the canal of Nuck. In both cases, the occurrence of an inguinal hernia on the contralateral side was noted

Clinical Outcome of Magnetic Resonance Imaging-Detected Additional Lesions in Breast Cancer Patients

Purpose: The aim of this study was to investigate the clinical outcome of additional breast lesions identified with breast magnetic resonance imaging (MRI) in breast cancer patients. Methods: A total of 153 patients who underwent breast MRI between July 2006 and March 2008 were retrospectively reviewed. Thirty-three patients (21.6%) were recommended for second-look ultrasound (US) for further characterization of additional lesions detected on breast MRI and these patients constituted our study population. Results: Assessment for lesions detected on breast MRI consisted of the following: 25 benign lesions (73.5%), two indeterminate (5.9%), and seven malignant (20.6%) in 33 patients. Second-look US identified 12 additional lesions in 34 lesions (35.3%) and these lesions were confirmed by histological examination. Of the 12 lesions found in the 11 patients, six (50.0%) including one contralateral breast cancer were malignant. The surgical plan was altered in 18.2 % (six of 33) of the patients. The use of breast MRI justified a change in treatment for four patients (66.7%) and caused two patients (33.3%) to undergo unwarranted additional surgical procedures. Conclusion: Breast MRI identified additional multifocal or contralateral cancer which was not detected initially on conventional imaging in breast cancer patients. Breast MRI has become an indispensable modality in conjunction with conventional modalities for preoperative evaluation of patients with operable breast cancer

Mutations in DDX58, which Encodes RIG-I, Cause Atypical Singleton-Merten Syndrome

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies

Mutations in DDX58, which Encodes RIG-I, Cause Atypical Singleton-Merten Syndrome

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.GLu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373A1a) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.X116452Ysciescopu