A Digital Coach (E-Supporter 1.0) to Support Physical Activity and a Healthy Diet in People With Type 2 Diabetes: Acceptability and Limited Efficacy Testing.

Background: A healthy lifestyle, including regular physical activity and a healthy diet, is increasingly part of type 2 diabetes (T2D) management. As many people with T2D have difficulty living and maintaining a healthy lifestyle, there is a need for effective interventions. eHealth interventions that incorporate behavior change theories and tailoring are considered effective tools for supporting a healthy lifestyle.

In Uveal Melanoma, Angiopoietin-2 but Not Angiopoietin-1 Is Increased in High-Risk Tumors, Providing a Potential Druggable Target.

Uveal melanoma (UM) metastasize haematogeneously, and tumor blood vessel density is an important prognostic factor. We hypothesized that proangiogenic factors such as angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2), two targetable cytokines, might play a role in tumor development and metastatic behavior. mRNA levels of ANG-1 and ANG-2 were determined in 64 tumors using an Illumina HT-12 v4 mRNA chip and compared to clinical, pathologic, and genetic tumor parameters.

Benzalkonium runoff from roofs treated with biocide products - In situ pilot-scale study.

Roof maintenance practices often involve the application of biocide products to fight against moss, lichens and algae. The main component of these products is benzalkonium chloride, a mixture of alkyl benzyl dimethyl ammonium chlorides with mainly C12 and C14 alkyl chain lengths, which is toxic for the aquatic environment. This paper describes, on the basis of an in-situ pilot scale study, the evolution of roof runoff contamination over a one year period following the biocide treatment of roof frames.

Analysis of quaternary ammonium compounds in urban stormwater samples.

A method for benzalkonium analysis has been developed to measure benzalkonium concentration in dissolved and particulate fractions from urban runoff samples. The analysis was performed by liquid chromatography coupled with mass spectrometry (LC-MS/MS). The dissolved matrix was extracted by Solid Phase Extraction (SPE), with cationic exchange and the particles by microwave extraction with acidified methanol.

MDMA-induced serotonergic neurotoxicity enhances aggressiveness in low- but not high-aggressive rats.

Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA) is a frequently (ab)used recreational drug for its acute euphoric effects but on the long-term may cause neurotoxic damage to serotonin (5-hydroxytryptamine; 5-HT) nerve endings in the brain. Since decreased brain 5-HT function has been strongly associated with several impulse control disorders like hostility and violent aggression, ecstasy users might be at risk developing this form of psychopathology. The present study examined the ability of a MDMA administration protocol (3 x 6 mg/kg, with 3h intervals at 25 degrees C ambient temperature), that previously was shown to partially deplete brain serotonin levels, to increase offensive aggressive behavior in male Wild-type Groningen (WTG) rats.

LIP5 interacts with aquaporin 2 and facilitates its lysosomal degradation.

Vasopressin binding to the V2 receptor in renal principal cells leads to activation of protein kinase A, phosphorylation of aquaporin 2 (AQP2) at Ser256, and the translocation of AQP2 to the apical membrane, resulting in concentration of the urine. In contrast, phorbol ester-induced activation of protein kinase C pathway leads to ubiquitination of AQP2 at Lys270 and its internalization to multivesicular bodies, where it is targeted for lysosomal degradation or stored for recycling. Because little is known about the regulation of AQP2 trafficking, we used the carboxy-terminal tail of constitutively nonphosphorylated AQP2 (S256A) as a bait for interacting proteins in a yeast two-hybrid assay.

Neurotoxicity marker profiles in the CSF are not age-dependent but show variation in children treated for acute lymphoblastic leukemia.

Background: In children treated for hematological malignancies, a transient elevation of the neurodegenerative marker Tau was found in the cerebrospinal fluid (CSF). In the first part of this study, CSF-Tau, CSF-Phospho-Tau, and CSF-Neuromodulin (CSF-NM) were measured in a heterogeneous group of patients presenting in the pediatric oncology department. In the second part, the neurodegenerative markers were analyzed in a group of children with non-B-cell acute lymphoblastic leukemia (nB-ALL) treated according to EORTC protocols 58881 and 58951.

Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies.

Children acquire neuropsychologic dysfunctions after chemotherapy for hematologic malignancy. In this study, putative changes in levels of CSF-tau (a marker of neural dysintegrity) in leukemic children prior to and during chemotherapy were studied. Cerebrospinal fluid (CSF) samples were obtained before and during treatment from patients with B cell non-Hodgkin's lymphoma (NHL, n = 10), non-B cell acute lymphoblastic leukemia/NHL (non-B-ALL, n = 48), acute myeloid leukemia (AML, n = 9), other malignant diseases (n = 9), and six control children.

In vitro and in vivo biocompatibility of dextran dialdehyde cross-linked gelatin hydrogel films.

The biosafety of a new hydrogel wound dressing material consisting of dextran dialdehyde cross-linked gelatin was evaluated (i) in vitro in cultures of dermal fibroblasts, epidermal keratinocytes, and endothelial cells, three cell types which play a major role in the process of cutaneous wound healing, and (ii) in vivo by subcutaneous implantation studies in mice. The cytotoxicities of this hydrogel, two semi-occlusive polyurethane dressings (Tegaderm and OpSite), and a hydrocolloid dressing (DuoDERM) were compared by measuring cell survival with the tetrazolium salt reduction (MTT) assay after incubations of the wound dressing samples for up to 6 d, in the presence of--but not in direct contact with--the cells. In vitro, the degree of cytotoxicity of the new hydrogel was greater in keratinocyte cultures than in fibroblast and endothelial cell cultures, and increased upon longer incubation time.

In vitro release characteristics of bioactive molecules from dextran dialdehyde cross-linked gelatin hydrogel films.

Hydrogel films, prepared by cross-linking of gelatin with dextran dialdehydes (weight ratio 2:1), and containing either fluorescein isothiocyanate dextran (Mw 70000) or polypeptides were evaluated in terms of their release characteristics and mechanical properties upon increasing storage time at 4 degrees C. Important changes in release kinetics and mechanical properties of the cross-linked gelatin films were observed, especially during the first week after the hydrogel production. Rheological and NMR measurements showed that the mechanical properties of the gelatin hydrogel films were improved with increasing storage time.

Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study.

Objectives: Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia.

Generation of a mouse tumor necrosis factor mutant with antiperitonitis and desensitization activities comparable to those of the wild type but with reduced systemic toxicity.

In this study, we investigated whether the recently identified lectin-like domain of tumor necrosis factor (TNF) is implicated in its biological activities on mammalian cells. To this end, a mouse TNF (mTNF) triple mutant, T104A-E106A-E109A mTNF (referred to hereafter as triple mTNF), lacking the lectin-like affinity of mTNF for specific oligosaccharides, was compared with the wild-type molecule for various TNF effects in vitro and in vivo. The triple mTNF displayed a 50-fold-reduced TNF receptor 2 (TNFR2)-mediated bioactivity but only a 5-fold-reduced TNFR1-mediated bioactivity in vitro.

Transmembrane segments critical for potassium channel function.

The relative contribution of the transmembrane segments in the alpha-subunit of Shaker-type potassium channels was investigated in relation to potassium channel function. Starting from a wild-type Kv1.1 channel, four different deletion mutants were made, missing respectively transmembrane segments S1 and S2, S2 and S3, S1 to S3, and S1 to S4.

The phosphorylation state of tau in the developing rat brain is regulated by phosphoprotein phosphatases.

The paired helical filaments (PHFs) in Alzheimer's disease neurofibrillary tangles are composed of PHF-tau which is thought to be hyperphosphorylated because several residues in postmortem samples of PHF-tau and human fetal tau are phosphorylated while the corresponding sites are not phosphorylated in autopsy-derived normal adult human brain tau. To determine how the phosphorylation of these sites is regulated, we isolated tau from rat brains at different embryonic and postnatal ages in the presence of okadaic acid to obtain tau in its most native in situ phosphorylation state. Fetal tau was highly phosphorylated from embryonic day 18 (E18) until postnatal day 11 (P11).

Characterization of a rat C6 glioma-secreted follistatin-related protein (FRP). Cloning and sequence of the human homologue.

A protein was isolated from rat C6 glioma-conditioned medium and was biochemically characterized. The heparin-binding protein has a native molecular mass of 55-75,000 Da, a molecular mass of 40-48,000 Da under denaturing conditions, and a pI of 5.0-6.

Secretion of steroids, growth factors, and cytokines by immortalized mouse granulosa cell lines.

The expression and function of gonadotropin receptors, and the secretion of steroids, transferrin, and cytokines were investigated in three immortalized (single transfection with v-myc) mouse granulosa cell lines (GRM01, GRM01L, and GRM02). A dose-dependent increase in progesterone production was obtained in GRM01 and GRM02 cells after addition of LH, FSH, modulators of the adenylate cyclase enzyme system, and cAMP analogues. The LH-induced release of progesterone was already detectable in GRM02 cells after 8 h and was related to incubation time and cell number.

Detection of tau proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay.

Alzheimer's disease is a progressive degenerative dementia characterized by the abundant presence of neurofibrillary tangles in neurons. This study was designed to test whether the microtubule-associated protein tau, a major component of neurofibrillary tangles, could be detected in CSF. Additionally, we investigated whether CSF tau levels were abnormal in Alzheimer's disease as compared with a large group of control patients.

Characterization of immortalized mouse granulosa cell lines.

Cell cultures of primary mouse granulosa cells were transfected with a v-myc-containing plasmid, and the resulting stable cell lines were tested for their steroidogenic properties and physiologic status. Granulosa cells were obtained from 22-day-old NMRI mice injected with 8 IU pregnant mare serum gonadotropin i.p.

Identification by microsequencing of lipopolysaccharide-induced proteins secreted by mouse macrophages.

The conditioned medium of the murine macrophage PU5.1.8 was analyzed by two-dimensional gel electrophoresis in order to detect LPS-induced proteins.

Magnetic beads in suspension enable a rapid and sensitive immunodetection of human placental alkaline phosphatase.

The kinetics and efficiency of the interaction between placental alkaline phosphatase and a monoclonal antibody (laboratory number 327) were determined by immunoassay using microtitre plates or magnetic beads. While only up to 45% of placental alkaline phosphatase was bound to microwells precoated with this antibody, even after prolonged incubation, no less than 60% and 100% binding were reached using magnetic beads after 1 and 3 h incubations, respectively. High-molecular-mass placental alkaline phosphatase and complexed placental alkaline phosphatase forms were also completely bound to magnetic beads in the presence of deoxycholate (up to 9 g/l for serum samples).

Production of functionally active murine and murine::human chimeric F(ab')2 fragments in COS-1 cells.

We report here the synthesis, in nonlymphoid cells, of two functionally active recombinant F(ab')2 fragments directed against the tumor marker, human placental alkaline phosphatase (hPLAP). The truncated heavy chain (HC) sequences, E6Hf2 and E6Hy3f2, of the murine F(ab')2 fragment, E6F2, and of the murine::human chimeric F(ab')2 fragment, E6(Hy3,kappa)F2, respectively, were engineered by introducing an in-phase stop codon within the second constant domain of the corresponding parental HC sequence. The antibody-encoding genes were placed under control of the simian virus 40 late promoter and each HC sequence, together with the light chain (LC) sequence, was transiently expressed in COS-1 cells.

Affinity purification of human tau proteins and the construction of a sensitive sandwich enzyme-linked immunosorbent assay for human tau detection.

Immunoaffinity chromatography with a monoclonal antibody produced against bovine tau protein was used to purify tau proteins from human brain. Fifty grams of brain tissue yielded approximately 2 mg of pure tau proteins. The affinity-purified human tau was used to produce a high-titered rabbit anti-human tau serum.

Monoclonal antibodies with selective specificity for Alzheimer Tau are directed against phosphatase-sensitive epitopes.

A modified form of the microtubule-associated protein Tau is the major component of the paired helical filaments (PHF) found in Alzheimer's disease. The characterization of these posttranslational Tau modifications is hindered by the lack of sufficient PHF-Tau-specific markers. Here we describe several monoclonal antibodies, prepared by immunization with PHF, two of which showed a selective specificity for PHF-Tau without cross-reactivity with normal Tau.

Specific monoclonal antibodies against normal microtubule-associated protein-2 (MAP2) epitopes present in Alzheimer pathological structures do not recognize paired helical filaments.

We have developed monoclonal antibodies that detect normal microtubule-associated protein-2 (MAP2) epitopes in routinely fixed, paraffin-embedded tissue. The somatodendritic distribution of MAP2 in bovine and human nervous tissue was confirmed with several of these antibodies. Furthermore, some of these antibodies immunohistochemically labeled certain pathological structures in Alzheimer brain, especially neurites in senile plaques.