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β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme to cleave the amyloid precursor protein to develop Alzheimer's disease (AD). Reducing BACE1 expression in central neuron through RNA interference technology shows great promise to overcome AD. However, to obtain an efficient and neurons-specific delivery of siRNA against BACE1 through systemic administration remains challenging. Here, we design and prepare siRNA nano-carriers based on PEGylated poly(2-(N,N-dimethylamino) ethyl methacrylate) (PEG-PDMAEMA) modified with both the CGN peptide for blood-brain barrier (BBB) penetration and the Tet1 peptide for neuron-specific binding...

Once infected by HIV-1, microglia abundantly produce accessory protein Nef that enhances virus production and infectivity, but little is known about its intracellular compartmentalization, trafficking mode(s), and release from microglia. Here, we transfected immortalized human microglia with a plasmid encoding Nef tagged with green fluorescent protein (Nef.GFP) to biochemically and microscopically identify Nef.GFP-associated cellular compartments and examine their mobility and Nef release from cultured cells...

Skin auto-fluorescence (SAF) has generated broad interest about the prospects for non-invasive advanced glycation end product assessment and its direct interplay with the development of microvascular complications, but clinical application of the existing SAF measuring of non-palmoplantar sites in non-Caucasian subjects with dark skin type is still controversial. Here, we tested the diabetic complication screening performance of a novel SAF measuring system in Asian type 2 diabetes mellitus (T2DM) subjects...

In this study, we screened PHB synthase PhaC1 and PHB depolymerase PhaZa1 of Ralstonia eutropha for the presence of phosphorylated residues during the PHB accumulation and PHB degradation phase. Thr373 of PHB synthase PhaC1 was phosphorylated in the stationary growth phase but was not modified in the exponential and PHB accumulation phases. Ser35 of PHB depolymerase PhaZa1 was identified in phosphorylated form both in the exponential and in the stationary growth phase. Additional phosphosites were identified for both proteins in sample-dependent forms...

High temperature (HT) stress is a major environmental stress that limits plant growth and development. Mitogen-activated protein kinase (MAPK) cascades play key roles in plant growth and stress signaling, but their involvement in the HT stress response are poorly understood. Here, we describe a 47-kDa MBP-phosphorylated protein (p47-MBPK) activated in tomato (Solanum lycopersicum) leaves under HT, and identify it as SlMPK1 by MS/MS analysis. Silencing of SlMPK1 in transgenic tomato plants resulted in enhanced tolerance to HT, while overexpression resulted in reduced tolerance...

AIM: To evaluate the role of adenovirus-mediated transduction human VEGF isoform 165 via direct myocardial injection in rats with an occluded circumflex coronary artery, and the possible underlying mechanism. METHODS: Sprague-Dawley rats were induced myocardial infarction (MI) with ligation of the left coronary artery. Rats were randomly divided into 4 groups: 1) the sham group; 2) the MI group; 3) the NS (normal saline) group and 4) the VEGF group. Direct myocardial injection of 0...

BACKGROUND: Stereotactic radioablation (SR), a commonly used therapy to treat malignancies, has been utilized to treat refractory ventricular tachycardia, but the feasibility of treating atrial fibrillation (AF) with SR is unknown. OBJECTIVE: We evaluated the safety and efficacy of SR targeting pulmonary vein (PV) antral tissues as potential therapy for AF. METHODS: Seventeen adult canines and two adult swine underwent surgical fiducial marker placement, 3D anatomic rendering CT angiogram of the left atrium (LA), and creation of a treatment plan targeting the right superior pulmonary veins (RSPVs)...

α-L-Rhamnosidases (α-RHAs, EC 3.2.1.40) are glycosyl hydrolases (GHs) hydrolyzing terminal α-L-rhamnose residues from different substrates such as heteropolysaccharides, glycosylated proteins and natural flavonoids. Although the possibility to hydrolyze rhamnose from natural flavonoids has boosted the use of these enzymes in several biotechnological applications over the past decades, to date only few bacterial rhamnosidases have been fully characterized and only one crystal structure of a rhamnosidase of the GH106 family has been described...

Proteinuria encompasses diverse causes including both genetic diseases and acquired forms such as diabetic and hypertensive nephropathy. The basis of proteinuria is a disturbance in size selectivity of the glomerular filtration barrier, which largely depends on the podocyte: a terminally differentiated epithelial cell type covering the outer surface of the glomerulus. Compromised podocyte structure is one of the earliest signs of glomerular injury. The phenotype of diverse animal models and podocyte cell culture firmly established the essential role of the actin cytoskeleton in maintaining functional podocyte structure...

PfPK7 is an "orphan" kinase displaying regions of homology to multiple protein kinase families. PfPK7 functions in regulating parasite proliferation/development as evident from the phenotype analysis of knockout parasites. Despite this regulatory role, the functions of PfPK7 in signaling pathways are not known. To better understand PfPK7-regulated phosphorylation events, we performed isobaric tag-based quantitative comparative phosphoproteomics of the schizont and segmenter stages from wild-type and pfpk7- parasite lines...

BACKGROUND: Researchers have theorized that increased rates of suicide in the military are associated with combat exposure; however, this hypothesis has received inconsistent support in the literature, potentially because combat exposure may be indirectly related to suicide risk through its influence on posttraumatic stress disorder (PTSD) and depressive symptoms. The current study tested the hypothesis that combat exposure has a significant indirect effect on suicidal behavior among Iraq/Afghanistan-era veterans through its effects on PTSD-depressive symptomatology...

Substituted N-cyclohexyl amides undergo aliphatic C-H bond oxidation with H2 O2 catalyzed by manganese complexes. The reactions are directed by torsional effects leading to site-selective oxidation of cis-1,4-, trans-1,3-, and cis-1,2-cyclohexanediamides. The corresponding diastereoisomers are unreactive under the same conditions. Competitive oxidation of cis- trans mixtures of 4-substituted N-cyclohexylamides leads to quantitative conversion of the cis-isomers, allowing isolation and successive conversion of the trans-isomers into densely functionalized oxidation products with excellent site selectivity and good enantioselectivity...

Hypohidrotic ectodermal dysplasia (HED) is characterized by hypohidrosis, hypodontia, sparse hair and characteristic facial features. This condition is caused by an ectodysplasin A (EDA) gene mutation. In this study, we examined two HED pedigrees and investigated the molecular genetics of the defect. Direct sequencing analysis revealed a previously unidentified mutation in the EDA splice donor site (c.526+1G>A). The function of the mutant EDA gene was predicted through online investigations and subsequently confirmed by splicing analysis in vitro...

OBJECTIVE Transient neurological events (TNEs) occur frequently in the acute phase after direct bypass surgery for moyamoya disease (MMD), but there is currently no way to predict them. FlowInsight is a specialized software for analyzing indocyanine green (ICG) videoangiography taken with a surgical microscope. The purpose of this study was to investigate whether intraoperative evaluation of local hemodynamic changes around anastomotic sites using FlowInsight could predict the incidence and duration of TNEs...

OBJECTIVE An implicit expectation of the pioneers of trauma system design was that high clinical volume at select centers could lead to superior outcomes. There has been little study of the regionalization of pediatric craniospinal trauma care, and whether it continues to trend in the direction of regionalization is unknown. The motivating hypothesis for this study was that trauma system design in the United States is proceeding on a rational basis, producing hospital caseloads that are increasing over time and, because of geographic siting appropriate to the needs of catchment areas, in an increasingly uniform manner...

B cell interaction with follicular helper T cells and their subsequent differentiation into high-affinity antibody producing cells normally takes place in secondary lymphoid organs. The costimulator ICOS plays a key role in this process and is therefore considered as an attractive target to modulate exaggerated B cell responses in autoimmune or allergic diseases. Inflamed tissues were recently recognized as additional sites of active T cell/B cell interaction. To analyze whether ICOS costimulation is also important there, we employed a mouse airway inflammation model which allows to directly compare immune reactions in the lung-draining lymph node and the lung tissue and also to assess the relative importance of dendritic cells versus B cells as antigen-presenting cells...

The Mo/Cu-dependent CO dehydrogenase (CODH) from Oligotropha carboxidovorans is an enzyme that is able to catalyze both the oxidation of CO to CO2 and the oxidation of H2 to protons and electrons. Despite the close to atomic resolution structure (1.1 Å), significant uncertainties have remained with regard to the reaction mechanism of substrate oxidation at the unique Mo/Cu-center, as well as the nature of intermediates formed during the catalytic cycle. So far the investigation of the role of amino acids at the active site was hampered due to the lack of a suitable expression system that allowed for detailed site-directed mutagenesis studies at the active-site...

Incomplete information regarding both selection regimes and the genetic basis of fitness limits our understanding of adaptive evolution. Among-year variation in the genetic basis of fitness is rarely quantified, and estimates of selection are typically based on single components of fitness, thus potentially missing conflicting selection acting during other life-history stages. Here, we examined among-year variation in selection on a key life-history trait and the genetic basis of fitness covering the whole life cycle in the annual plant Arabidopsis thaliana...

Pselaphinae is a species-rich beetle subfamily found globally, with many exhibiting myrmecophily-a symbiotic association with ants. Pselaphine-ant associations vary from facultative to obligate, but direct behavioral observations still remain scarce. Pselaphines are speciose and ecologically abundant within tropical leaf litter invertebrate communities where ants dominate, implying a potentially important ecological role that may be affected by habitat disturbances that impact ants. In this study, we measured and analyzed putative functional traits of leaf litter pselaphines associated with myrmecophily through morphometric analysis...

Porous ternary metal sulfide integrated electrode materials with abundant electroactive sites and redox reactions are very promising for supercapacitors. Here, porous zinc cobalt sulfide nanosheets array on Ni foam (Zn-Co-S/NF) has been successfully constructed by a facile growth of 2D bimetallic zinc/cobalt-based metal-organic frameworks (Zn/Co-MOF) nanosheets with leaf-like morphology on Ni foam, followed by additional sulfurization. The Zn-Co-S/NF nanosheets array is directly acted as an electrode for supercapacitor, showing much better electrochemical performance (2354...