Macrophage IKKα Deficiency Suppresses Akt Phosphorylation, Reduces Cell Survival, and Decreases Early Atherosclerosis.

Objective: The IκB kinase (IKK) is an enzyme complex that initiates the nuclear factor κB transcription factor cascade, which is important in regulating multiple cellular responses. IKKα is directly associated with 2 major prosurvival pathways, PI3K/Akt and nuclear factor κB, but its role in cell survival is not clear. Macrophages play critical roles in the pathogenesis of atherosclerosis, yet the impact of IKKα signaling on macrophage survival and atherogenesis remains unclear.

Structural elucidation of AgAsS2 glass by the analysis of clusters formed during laser desorption ionisation applying quadrupole ion trap time-of-flight mass spectrometry.

Rationale: The structure of AgA(s)S2 glass, which has a broad range of applications, is still not well understood and a systematic mass spectrometric analysis of AgA(s)S2 glass is currently not available. Elucidation of the structure should help in the development of this material.

Methods: The AgA(s)S2 glass was prepared by the melt-quenched technique.

Preparation of hydrophilic monolithic capillary column by in situ photo-polymerization of N-vinyl-2-pyrrolidinone and acrylamide for highly selective and sensitive enrichment of N-linked glycopeptides.

In this study, a novel kind of amide functionalized hydrophilic monolith was synthesized by the in situ photo-polymerization of N-vinyl-2-pyrrolidinone (NVP), acrylamide (AM), and N, N'-methylenebisacrylamide (MBA) in a UV transparent capillary, and successfully applied for hydrophilic interaction chromatography (HILIC) based enrichment of N-linked glycopeptides. With 2 μg of the tryptic digests of IgG as the sample, after enrichment, 18 glycopeptides could be identified by MALDI-TOF/TOF MS analysis. Furthermore, with the mixture of BSA and IgG digests (10,000:1, m/m) as the sample, 6 N-linked glycopeptides were unambiguously identified after enrichment, indicating the high selectivity and good specificity of such material.

Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia.

A functional complex consisting of androgen receptor (AR) and forkhead box A1 (FOXA1) proteins supports prostatic development, differentiation, and disease. In addition, the interaction of FOXA1 with cofactors such as nuclear factor I (NFI) family members modulates AR target gene expression. However, the global role of specific NFI family members has yet to be described in the prostate.

Effect of oral N-acetylcysteine on COPD patients with microsatellite polymorphism in the heme oxygenase-1 gene promoter.

Background: Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung, and HO-1 gene promoter polymorphism has been shown to be associated with the severity and prognosis of COPD patients. N-acetylcysteine (NAC), an antioxidant/mucous modifier, has shown an uncertain benefit in COPD patients. We hypothesized that this polymorphism could be associated with the effectiveness of oral NAC.

Patients with Rheumatoid Arthritis have Similar Excellent Outcomes after Total Knee Replacement Compared with Patients with Osteoarthritis.

Objective: Although new treatments for rheumatoid arthritis (RA) are extremely effective in preventing disease progression, rates of total knee replacement (TKR) continue to rise. The ongoing need for TKR is problematic, especially as functional outcomes in patients with RA have been reported to be worse than in patients with osteoarthritis (OA). The purpose of this study is to assess pain, function, and quality of life 2 years after TKR in contemporary patients with RA compared with patients with OA.

Utility and Significance of Gadolinium-Based Contrast Enhancement in Posterior Reversible Encephalopathy Syndrome.

Background And Purpose: Posterior reversible encephalopathy syndrome is a clinicoradiologic syndrome. Literature regarding associated factors and the prognostic significance of contrast enhancement in posterior reversible encephalopathy syndrome is sparse. This study set out to evaluate an association between the presence of enhancement in posterior reversible encephalopathy syndrome and various clinical factors in a large series of patients with this syndrome.

Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models.

Introduction: Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer's disease (AD). Aβ also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) ɛ4 is associated with increases in both Aβ plaques and CAA in humans.

Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera.

Respiratory syncytial virus (RSV) is estimated to claim more lives among infants <1 year old than any other single pathogen, except malaria, and poses a substantial global health burden. Viral entry is mediated by a type I fusion glycoprotein (F) that transitions from a metastable prefusion (pre-F) to a stable postfusion (post-F) trimer. A highly neutralization-sensitive epitope, antigenic site Ø, is found only on pre-F.

Structural MRI substrates of cognitive impairment in neuromyelitis optica.

Objective: To identify the clinical and structural MRI markers for predicting cognitive impairment (CI) in patients with neuromyelitis optica (NMO).

Methods: Fifty-four patients with NMO and 27 healthy controls underwent extensive neuropsychological testing and multimodal 3.0T MRI.

Interferon-γ-mediated allograft rejection exacerbates cardiovascular disease of hyperlipidemic murine transplant recipients.

Rationale: Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors.

Objective: To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients.

A Prussian Blue-Based Core-Shell Hollow-Structured Mesoporous Nanoparticle as a Smart Theranostic Agent with Ultrahigh pH-Responsive Longitudinal Relaxivity.

Novel core-shell hollow mesoporous Prussian blue @ Mn-containing Prussian blue analogue (HMPB@MnPBA) nanoparticles, designated as HMPB-Mn) as an intelligent theranostic nanoagent, are successfully constructed by coating a similarly crystal-structured MnPBA onto HMPB. This can be used as a pH-responsive T1 -weighted magnetic resonance imaging contrast agent with ultrahigh longitudinal relaxivity (r1 = 7.43 m m(-1) s(-1) ), and achieves the real-time monitoring of drug release.

GDF11 does not rescue aging-related pathological hypertrophy.

Rationale: Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH) and restoring GDF11 to normal levels in old mice rescued PCH.

Objective: To determine whether and by what mechanism GDF11 rescues aging dependent PCH.

HDAC5-mTORC1 Interaction in Differential Regulation of Ghrelin and Nucleobindin 2 (NUCB2)/Nesfatin-1.

Sodium valporate (VPA), a broad-spectrum inhibitor of histone deacetylases (HDACs), increased ghrelin whereas decreased nesfatin-1 in mice fed normal chow diet or high-fat diet. Alterations in ghrelin and nucleobindin 2/nesfatin-1 were mediated by HDAC5 but not HDAC4. Activation of mTORC1 significantly attenuated the effect of VPA on ghrelin and nesfatin-1 levels.

[Comparison of cranial-to-caudal medial versus traditional medial approach in laparoscopic right hemicolectomy: a case-control study].

Objective: To compare the short-term efficacy of modified medial (M-M) with traditional medial(T-M) approach in laparoscopic right hemicolectomy(LRHC)/or extended laparoscopic right hemicolectomy(ELRHC) for right or hepatic flexure colon cancer.

Methods: A comparative, retrospective study was performed that included all the patients scheduled for LRHC or ELRHC for right or hepatic flexure colon cancer between June 2013 and August 2014. The following factors of two groups were assessed: patient characteristics, operative details, pathology, and surgical outcomes.

Exposure of Human Prostaspheres to Bisphenol A Epigenetically Regulates SNORD Family Noncoding RNAs via Histone Modification.

Bisphenol A (BPA) is a ubiquitous endocrine disruptor exerting lifelong effects on gene expression in rodent prostate cancer (PCa) models. Here, we aimed to determine whether epigenetic events mediating the action of BPA on human prostaspheres enriched in epithelial stem-like/progenitor cells is linked to PCa. We performed genome-wide transcriptome and methylome analyses to identify changes in prostaspheres treated with BPA (10 nM, 200 nM, and 1000 nM) or estradiol-17β (E2) (0.

Brain Default Mode Network Changes after Renal Transplantation: A Diffusion-Tensor Imaging and Resting-State Functional MR Imaging Study.

Purpose: To investigate structural and functional alterations of the default mode network (DMN) in the brain after renal transplantation in patients with end-stage renal disease by using diffusion-tensor imaging and resting-state functional MR imaging.

Materials And Methods: This prospective study was approved by the local medical research ethics committee, and written informed consent was obtained. Twenty-one patients with end-stage renal disease (15 men, six women; mean age ± standard deviation, 32 years ± 9.

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients.

Sphingosine 1-Phosphate Produced by Sphingosine Kinase 2 Intrinsically Controls Platelet Aggregation In Vitro and In Vivo.

Rationale: Platelets are known to play a crucial role in hemostasis. Sphingosine kinases (Sphk) 1 and 2 catalyze the conversion of sphingosine to the bioactive metabolite sphingosine 1-phosphate (S1P). Although platelets are able to secrete S1P on activation, little is known about a potential intrinsic effect of S1P on platelet function.

Ablation of Lgr4 enhances energy adaptation in skeletal muscle via activation of Ampk/Sirt1/Pgc1α pathway.

Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a newfound obese-associated gene. Previous study reveals that heterozygous mutation of Lgr4 correlates with decreased body weight in human. In our recent study, we demonstrate that Lgr4 ablation promotes browning of white adipose tissue and improves whole-body metabolic status.

Linear 3d-4f compounds: synthesis, structure, and determination of the d-f magnetic interaction.

A family of [RE2M2L2(BA)6] (RE = Gd, Tb, Dy, Y; M = Co, Ni, Cu, Zn; L = 1,2-bis(2-hydroxy-3-methoxybenzylidene)hydrazine; BA = benzoic acid) complexes were synthesized and structurally and magnetically characterized. The magnetic interactions between spin centers were systematically investigated. The interactions of M-M (M = Co, Ni and Cu) and Gd-Ni/Cu were extracted from the fitting of the experimental data of Y2M2 (M = Co, Ni and Cu) and Gd2M2 (M = Ni and Cu) derivatives, respectively.

Bioengineering Novel Chimeric microRNA-34a for Prodrug Cancer Therapy: High-Yield Expression and Purification, and Structural and Functional Characterization.

Development of anticancer treatments based on microRNA (miRNA/miR) such as miR-34a replacement therapy is limited to the use of synthetic RNAs with artificial modifications. Herein, we present a new approach to a high-yield and large-scale biosynthesis, in Escherichia coli using transfer RNA (tRNA) scaffold, of chimeric miR-34a agent, which may act as a prodrug for anticancer therapy. The recombinant tRNA fusion pre-miR-34a (tRNA/mir-34a) was quickly purified to a high degree of homogeneity (>98%) using anion-exchange fast protein liquid chromatography, whose primary sequence and post-transcriptional modifications were directly characterized by mass spectrometric analyses.

Interaction between phosphorus removal and hybrid granular sludge formation under low hydraulic selection pressure at alternating anaerobic/aerobic conditions.

The hybrid granular sludge (HGS) formation and its performances on phosphorus removal were investigated in a sequencing batch airlift reactor. Under conditions of low superficial air velocity (SAV = 0.68 cm s(-1)) and relatively long settling time (15-30 min), aerobic granules appeared and coexisted with bio-flocs after 120 days operation.

Solventless Formation of G-Quartet Complexes Based on Alkali and Alkaline Earth Salts on Au(111).

Template cations have been extensively employed in the formation, stabilization and regulation of structural polymorphism of G-quadruplex structures in vitro. However, the direct addition of salts onto solid surfaces, especially under ultra-high-vacuum (UHV) conditions, to explore the feasibility and universality of the formation of G-quartet complexes in a solventless environment has not been reported. By combining UHV-STM imaging and DFT calculations, we have shown that three different G-quartet-M (M: Na/K/Ca) complexes can be obtained on Au(111) using alkali and alkaline earth salts as reactants.

Modeling transmembrane domain dimers/trimers of plexin receptors: implications for mechanisms of signal transmission across the membrane.

Single-pass transmembrane (TM) receptors transmit signals across lipid bilayers by helix association or by configurational changes within preformed dimers. The structure determination for such TM regions is challenging and has mostly been accomplished by NMR spectroscopy. Recently, the computational prediction of TM dimer structures is becoming recognized for providing models, including alternate conformational states, which are important for receptor regulation.