High-Fat Diet-Induced Diabetic Conditions Exacerbate Cognitive Impairment in a Mouse Model of Alzheimer's Disease Via a Specific Tau Phosphorylation Pattern.

BACKGROUND: Epidemiological evidence has demonstrated a clear association between diabetes mellitus and increased risk of Alzheimer's disease (AD). Cerebral accumulation of phosphorylated tau aggregates, a cardinal neuropathological feature of AD, is associated with neurodegeneration and cognitive decline. Clinical and experimental studies indicate that diabetes mellitus affects the development of tau pathology; however, the underlying molecular mechanisms remain unknown. OBJECTIVE: In the present study, we used a unique diabetic AD mouse model to investigate the changes in tau phosphorylation patterns occurring in the diabetic brain. DESIGN: Tau-transgenic mice were fed a high-fat diet (n = 24) to model diabetes mellitus. These mice developed prominent obesity, severe insulin resistance, and mild hyperglycemia, which led to early-onset neurodegeneration and behavioral impairment associated with the accumulation of hyperphosphorylated tau aggregates. RESULTS: Comprehensive phosphoproteomic analysis revealed a unique tau phosphorylation signature in the brains of mice with diabetic AD. Bioinformatic analysis of the phosphoproteomics data revealed putative tau-related kinases and cell signaling pathways involved in the interaction between diabetes mellitus and AD. CONCLUSION: These findings offer potential novel targets that can be used to develop tau-based therapies and biomarkers for use in AD.

Dataset of operating conditions to Isolate Cellulose Nanocrystalline from Sugarcane Bagasse and Pinewood Sawdust as Possible Material to Fabricate Polymer Electrolyte Membranes.

The data shown in this document provides all the experimental data that complement the article published in Carbohydrate Polymers entitled "Influence of operating conditions on Proton Conductivity of Nanocellulose films using two Agroindustrial Wastes: Sugarcane Bagasse and Pinewood Sawdust" [1]. The data of this paper are the result of a large series of experiments to optimize the extraction of cellulose nanocrystalline (CNC) from these two agro-industrial wastes: sugarcane Bagasse (SCB) and pinewood sawdust (PSW). The conditions of pretreatment (5 wt.% or 10 wt.% of NaOH) and hydrolysis temperature (60, 75 and 90°C) in an aqueous solution of 45 wt.% of H2SO4 were analyzed exhaustively. The data includes the characterization by Fourier transform infrared (FT-IR), Differential Scanning Calorimetry/Thermogravimetric Analysis (DSC/TGA), Dynamic Light Scattering (DLS), X-ray diffraction (XRD) patterns, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) micrographs with their corresponding SAED patterns and nanoindentation tests. Additionally, photographs during the isolation of cellulose nanocrystalline in dependence of the syntheses parameters. It is also included the data that complement the molecular dynamic simulation generated by GLYCAM carbohydrate builder based on the coordinates for alpha and beta cellulose considering a microfibril of 5, 10 and 20 glucosyl residues (degree of polymerization, DP). Overall data have not been previously published and are available contributing to a better understanding of the CNCs isolation through different pretreatment concentrations and temperatures of processing.

Influence of operating conditions on proton conductivity of nanocellulose films using two agroindustrial wastes: Sugarcane bagasse and pinewood sawdust.

Cellulose nanocrystals (CNCs) were isolated from two-agroindustrial wastes: sugarcane bagasse (SCB) and pinewood sawdust (PWS), to analyze their chemical, structural, morphological, and proton conduction properties in dependence of the synthesis parameters. In both sources, the isolated CNCs correspond to the monoclinic phase of cellulose type I and II. For SCB, the smallest CNCs were isolated, in a range of 3-10 nm, with 5 wt.% of NaOH and 60 °C of acid hydrolysis. PWS displayed the smallest sizes at 75 °C and 10 wt.% NaOH (40-110 nm). Membrane characterization suggests that isolated CNCs, between 75 and 90 °C of acid hydrolysis and 10 wt.% NaOH from both SCB and PWS sources, displayed an important increase in the proton conductivity, 1.23(±0.61)×10-5 and 9.26 (±0.24)×10-5 S-m-1, respectively. Thus, with proper synthesis conditions, CNCs can be potentially used as based element to obtain other proton conductor materials to fabricate PEMs.

Data supporting the elemental composition, the morphological and thermal properties of MnPhos/waterborne poly(urethane)(WPU) coatings for carbon steel.

The data set presented here offers evidence of the elemental composition related to a SEM micrograph of [Mn5(PO3(OH))2(PO4)2⋅4H2O] (MnPhos) powders, known as hurealite, and synthesized by the reflux method. In addition, it contains additional information of the glass transition, melting and decomposition temperatures and their weight loss percent of coatings based on MnPhos incorporated into waterborne poly(urethane) (WPU). These data are complementing of the article "Corrosion investigation of new hybrid organic/inorganic coatings for carbon steel substrates: electrochemical and surface characterizations".

Dataset on electrochemical reduced graphene oxide production: Effect of synthesis parameters.

Structural and microstructural characterization combined with vibrational, rotational modes are quite important to determinate reduction degree during synthesis of reduced graphene oxide. These data and analysis support the research article "Electrochemical alternative to obtain reduced graphene oxide by pulse potential: effect of synthesis parameters and study of corrosion properties" (López-Oyama et al., 2018). The data and analysis presented here included raw data for selected reduction potentials (V SCE) and different temperatures values (°C). Transmission electron microscopy (TEM) images of the exfoliated graphite are shown to corroborate the effect of the applied voltage to obtain electrochemically reduced graphene oxide (ERGO) on commercial 304L stainless steel (304L SS). The data provided in this article has not been previously published and are available to enable critical or extended analyses.

Lactate increases myotube diameter via activation of MEK/ERK pathway in C2C12 cells.

AIM: Lactate is produced in and released from skeletal muscle cells. Lactate receptor, G-protein-coupled receptor 81 (GPR81), is expressed in skeletal muscle cells. However, a physiological role of extracellular lactate on skeletal muscle is not fully clarified. The purpose of this study was to investigate extracellular lactate-associated morphological changes and intracellular signals in C2C12 skeletal muscle cells. METHODS: Mouse myoblast C2C12 cells were differentiated for 5 days to form myotubes. Sodium lactate (lactate) or GPR81 agonist, 3,5-dihydroxybenzoic acid (3,5-DHBA), was administered to the differentiation medium. RESULTS: Lactate administration increased the diameter of C2C12 myotubes in a dose-dependent manner. Administration of 3,5-DHBA also increased myotube diameter. Not only lactate but also 3,5-DHBA upregulated the phosphorylation level of mitogen-activated protein kinase kinase 1/2 (MEK1/2), p42/44 extracellular signal-regulated kinase-1/2 (ERK1/2) and p90 ribosomal S6 kinase (p90RSK). MEK inhibitor U0126 depressed the phosphorylation of ERK-p90RSK and increase in myotube diameter induced by lactate. On the other hand, both lactate and 3,5-DHBA failed to induce significant responses in the phosphorylation level of Akt, mammalian target of rapamycin, p70 S6 kinase and protein degradation-related signals. CONCLUSION: These observations suggest that lactate-associated increase in the diameter of C2C12 myotubes is induced via activation of GRP81-mediated MEK/ERK pathway. Extracellular lactate might have a positive effect on skeletal muscle size.

Vesiculobullous melanoma: an unusual manifestation of in-transit metastasis.

Malignant melanoma (MM), a well-known skin cancer with a poor prognosis, has various clinical manifestations, but vesiculobullous lesions have seldom been reported. We report a case of MM forming amelanotic vesicles at the site of an in-transit metastasis, and we also review the published reports on vesiculobullous MM. Our patient was an 87-year-old man with a history of a treated plantar MM 2 years previously, who had recurrence of the MM and development of an in-transit metastasis in his lower leg. Histopathological findings revealed vesicles caused by infiltration of the tumour. A review of the English literature revealed nine cases with various clinical presentations of the vesicles or blisters. For patients with MM with vesiculobullous lesions, an accurate medical history and examination of biopsies are of primary importance for management.

Reconstruction of low hairline microtia of Treacher Collins syndrome with a hinged mastoid fascial flap.

Treacher Collins syndrome (TCS) is a rare genetic disorder leading to congenital craniofacial malformations. Although this syndrome presents with various symptoms, corrective surgery for bilateral microtia with low hairline is one of the most challenging operations given the complex contours of the external ear. In this technical note, a novel, simple procedure for dealing with the low hairline by using a hinged mastoid fascial flap simultaneously with costal cartilage grafting is described. Several techniques for the reconstruction of low hairline microtia have been reported previously, such as skin graft, skin flap, and tissue expander, but the high number of repeat operations and residual scars remain problematic. As a simultaneous procedure with framework grafting, the use of a temporoparietal flap with skin grafting is popular; however, its drawbacks include the operative scar, decreased hair growth, and hair thinning. Patients with TCS show anatomical variations of the superficial temporal vessels supplying the temporoparietal flap. In contrast, due to the high vascularity of the mastoid fascia, the mastoid fascial flap can be elevated safely and easily as an anteriorly, posteriorly, superiorly, or inferiorly based flap.

Structure, electronic properties, and aggregation behavior of hydroxylated carbon nanotubes.

We present a combined experimental and theoretical study to analyze the structure, electronic properties, and aggregation behavior of hydroxylated multiwalled carbon nanotubes (OH-MWCNT). Our MWCNTs have average diameters of ~2 nm, lengths of approximately 100-300 nm, and a hydroxyl surface coverage θ~0.1. When deposited on the air/water interface the OH-MWCNTs are partially soluble and the floating units interact and link with each other forming extended foam-like carbon networks. Surface pressure-area isotherms of the nanotube films are performed using the Langmuir balance method at different equilibration times. The films are transferred into a mica substrate and atomic force microscopy images show that the foam like structure is preserved and reveals fine details of their microstructure. Density functional theory calculations performed on model hydroxylated carbon nanotubes show that low energy atomic configurations are found when the OH groups form molecular islands on the nanotube's surface. This patchy behavior for the OH species is expected to produce nanotubes having reduced wettabilities, in line with experimental observations. OH doping yields nanotubes having small HOMO-LUMO energy gaps and generates a nanotube → OH direction for the charge transfer leading to the existence of more hole carriers in the structures. Our synthesized OH-MWCNTs might have promising applications.

Effectiveness of combined pulsed dye and Q-switched ruby laser treatment for large to giant congenital melanocytic naevi.

BACKGROUND: There is no consensus on the most appropriate treatment for patients with large to giant congenital melanocytic naevi (CMN) because of the risk of melanoma development. Surgical excision followed by skin grafting or expanded skin coverage may cause unfavourable scarring. There is a balance to be achieved between minimizing the disfiguring appearance and the risk of malignant change. The pulsed dye laser (PDL) is commonly used for vascular lesions and is highly absorbed by melanin and haemoglobin. Its pulse duration is longer than that of Q-switched ruby lasers (QsRL), which can have nonspecific photothermolytic effects on surrounding nonpigmented naevus cells. OBJECTIVES: To investigate the effectiveness of combined treatment with the PDL and QsRL for large to giant CMN. METHODS: Six patients with large to giant CMN were enrolled in this study. Treatment consisted of one pass of PDL treatment followed by one pass of QsRL treatment. Multiple rounds of treatment were applied to all patients. RESULTS: All patients responded to this combined regimen, and the lesional colour was effectively reduced. The mean number of rounds of laser treatment required to achieve skin lightening was 7·7. No patients suffered severe hypertrophic scarring. No cases of recurrence or malignant transformation were observed. The histological results from the patient who underwent the most laser therapy in this study showed a remarkable reduction in the number of melanocytic naevus cells after treatment. CONCLUSIONS: This technique may enable the removal of most of the pigmented lesion and melanocytic naevus cells with minimal scarring.

Reconstructive considerations in the treatment of soft tissue sarcomas of the cheek.

Soft tissue sarcomas of the head and neck region are rare, and very little has been described about the reconstructive methods used after sarcoma resection of cheek soft tissue sarcomas. Reconstructive methods for cheek defects after sarcoma resection are presented and the possibilities, advantages, disadvantages, and expected results are described. A series of 3 patients with cheek soft tissue sarcomas were examined. Reconstructive methods included; one skin graft, a free forearm flap and a cervicofacial flap. All patients had lesions < 5 cm and low-grade tumours, and no case presented local recurrence or metastases. The choice of reconstructive methods depends mostly on the complexity of the defect. In cases comprising comparatively small or minor defects, reconstructions using local flaps, such as the cervicofacial flap, provide better aesthetic and functional results than either free flaps or skin graft.

Interaction of the cationic peptide bactenecin with phospholipid monolayers at the air-water interface: i interaction with 1,2-dipalmitoyl-sn-glycero-3-phosphatidilcholine.

In this work we have investigated the influence of NaCl on the adsorption of the antimicrobial cationic peptide bactenecin in the monolayer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at the air-water interface, as a function of NaCl concentrations in the subphase. We show that the effect of the salt concentration on DPPC monolayers is a monotonic decrease of the liquid-condensed-liquid-expanded (LC-LE) coexistence region. By contrast, the effect of the bactenecin adsorption at the DPPC monolayer not only removed the LC-LE coexistence region plateau, but also shifted the DPPC isotherms to higher pressures and increased the compressibility of the DPPC/bactenecin monolayers with respect to the pure DPPC monolayer around the LC phase. Analysis of the domain structure, obtained by Brewster angle and atomic force microscopes, indicates that the salt concentration in the subphase builds an electrostatic barrier, increasing the rigidity of DPPC monolayers and limiting the bactenecin adsorption at the LC-LE phase coexistence.

Surgical rehabilitation of reversible facial palsy: facial--hypoglossal network system based on neural signal augmentation/neural supercharge concept.

To obtain symmetric appearance in facial palsy patients, it is important to retain any remaining potential of the compromised facial mimetic muscles. The purpose of the present study was to introduce surgical rehabilitation based on neural signal augmentation/neural supercharge concept for the treatment of reversible facial palsy patients. With construction of facial-hypoglossal network system using end-to-side neurorrhaphy technique, both facial and hypoglossal motor signals are provided to the compromised facial mimetic muscles. It is hypothesised that the remaining potential of incompletely or completely paralysed muscles without atrophy is activated by a neural 'supercharge' effect. To date, nine patients presented with reversible facial palsy have been treated by surgical rehabilitation with facial-hypoglossal network system in our institutes. Facial mimetic muscle function evaluated by the House-Brackmann grading system was improved from grade IV-VI to II-III in this series. The postoperative ENMG findings showed double innervation of the mimetic muscles supplied by the facial and hypoglossal donor motor sources. Hemiglossal dysfunction and mimetic muscle synkinesis associated with tongue motion were never seen with an average follow-up period of 21 months after surgery. This reconstructive concept offers a significant advantage for the treatment of the facial palsy patients with persistent incomplete type and reversible complete type without distinct mimetic muscle atrophy.

Two innovations of the star-flap technique for nipple reconstruction.

Two innovations of the star-flap technique for nipple reconstruction are described. A combination of the star-flap technique and a contralateral nipple graft is indicated in patients with a large nipple and small areola on the contralateral side. It provides sufficient volume for the new nipple and improves the shape of the donor nipple. A combination of the star-flap technique and a banked costal-cartilage graft offers better nipple contour and projection than the conventional star-flap technique. Preparation of the cartilage graft is easy and does not result in additional scarring; the nipple projection can be expected to be maintained over a long period.

Altered cultured mesangial cell phenotypes from RF/J mice: a spontaneous immune complex mediated glomerulonephritis with progressive glomerulosclerosis.

BACKGROUND/AIM: RF/J mice are a model of spontaneous immune complex mediated glomerulonephritis showing massive extracellular matrix accumulation and progressive glomerulosclerosis. The aim of this study was to investigate whether there is an altered cultured mesangial cell (MC) phenotype in RF/J mice associated with these glomerular changes. METHODS: The nature of cultured MCs from RF/J mice in the proliferative response to platelet-derived growth factor (PDGF) BB was compared with that of normal mice (BALB/c) by 3H-thymidine incorporation. The binding of PDGF-BB was examined with Scatchard analysis, and the messenger RNAs (mRNAs) of PDGF beta-receptor, collagen I, collagen IV, and fibronectin were detected using Northern blot analysis in the MCs of each mouse. RESULTS: The 3H-thymidine incorporation of MCs from RF/J mice showed significantly lower responses to PDGF-BB stimulations with concentrations ranging from 0.5 to 10.0 ng/ml in comparison with those of BALB/c mice which exhibited a proportional dose- dependent increase of the incorporation (p < 0.05 for 0.5 ng/ml PDGF-BB, p < 0.01 for 1.0-10.0 ng/ml). According to the Scatchard analysis, MCs from BALB/c mice showed aKD of 105 pM of PDGF-BB binding to its receptors, and the density of receptors was 5.82 fmol/10(5) cells. However, no binding PDGF-BB site on the surface of MCs from RF/J mice was noted. Northern blot analysis of MCs from RF/J mice indicated negative expression of detectable PDGF-beta receptor mRNA. As for matrix protein messages, MCs from RF/J mice did not express mRNA of type I collagen, but did express a higher amount of type IV collagen and fibronectin in comparison with MCs from normal BALB/c mice. CONCLUSIONS: An altered phenotype in MCs of RF/J mice was demonstrated, possibly contributing to the characteristic pathological glomerular changes. However, the precise association remains to be clarified.

Crosstalk of prolyl isomerases, Pin1/Ess1, and cyclophilin A.

Previous studies have indicated that Ess1/Pin1, a gene in the parvulin family of peptidyl-prolyl isomerases (PPIases), plays an important role in regulating the G(2)/M transition of the cell cycle by binding cell-cycle-regulating proteins in eukaryotic cells. Although the ess1 gene has been considered to be essential in yeast, we have isolated viable ess1 deletion mutants and demonstrated, via analysis of yeast gene expression profiles using microarray techniques, a novel regulatory role for ESS1 in the G(1) phase. Although the overall expression profiles in the tested strains (C110-1, W303, S288c, and RAY-3AD) were similar, marked changes were detected for a number of genes involved in the molecular action of ESS1. Among these, the expression levels of a cyclophilin A gene, also a member of the PPIase family, increased in the ess1 null mutant derived from C110-1. Subsequent treatment with cyclosporin A significantly retarded growth, which suggests that ESS1 and cyclophilin A are functionally linked in yeast cells and play important roles at the G(1) phase of the cell cycle.

An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome with chronic renal failure.

A 25-year-old man developed a stroke-like episode. He suffered from renal failure and became dialysis-dependent. His mother was also dialysis-dependent. A3243G point mutation of the mitochondrial tRNA(leu) gene was detected in both of them. The patient was diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), and died of a recurrence of stroke-like episodes at the age of 30. Autopsy revealed numerous abnormal mitochondria in the kidneys, but no renal vascular changes. This is the first report of a MELAS case in which the presence of numerous abnormal mitochondria in podocytes and tubules was confirmed by electron microscopy.

Up-regulated TGF-beta mRNA expression in splenic T cells of high IgA-prone mice: a murine model of IgA nephropathy with glomerulosclerosis.

BACKGROUND/AIMS: Recently, we established a high serum IgA-prone inbred (HIGA) mouse strain as a murine model of spontaneous IgA nephropathy by selective mating of high serum IgA ddY mice, and found that they showed enhanced production of glomerular extracellular matrix components with increased expression of TGF-beta mRNA and protein in the kidneys. In this study, we examined the roles of lymphocytes in the development of high serum IgA in this strain. METHODS: We performed flow cytometric analyses of T and B cells in splenic mononuclear cells (SMNCs) from these mice using BALB/c mice as normal controls. We also compared serum TGF-beta1 concentrations and TGF-beta mRNA expression levels in the B-cell-depleted (T-cell-rich) fraction of SMNCs in these mice. RESULTS: HIGA mice showed significantly fewer CD3-positive cells compared with BALB/c mice when young, but not when aged. The CD4/CD8 ratio of HIGA mice was lower than that of BALB/c mice, but this difference was not significant. Although the number of B220-positive cells did not vary significantly, the ratio of surface IgA-positive B cells was significantly increased in both young and adult HIGA mice. The B-cell-depleted SMNCs from HIGA mice exhibited higher levels of expression of TGF-beta and TGF-beta1 mRNA than controls from a young age, which were maintained throughout life, but there were no differences in PDGF, MCP-1 or bFGF expression between these two strains. In contrast to local mRNA expression, serum TGF-beta1 concentration was decreased in HIGA mice compared with BALB/c controls. CONCLUSION: These findings suggest that the mating procedure performed to establish HIGA mice selected for a unique phenotype of local up-regulation of TGF-beta production in the kidneys, as well as T cells that may contribute to both the early and consistently high serum IgA expression and enhanced production of renal extracellular matrix components in HIGA mice. Additionally, TGF-beta1 may act locally, not systemically, in a paracrine or autocrine manner.