Anti-nociceptive and anti-inflammatory activities of extract of Anchomanes difformis in rats

Anchomanes difformis is a tropical plant that has been used in folklore to treat diverse complications. The leaf extract of A. difformis was investigated for possible anti-nociceptive and anti-inflammatory effects in albino wistar rats. In these independent studies, two sets of twenty five rats were divided into five groups of five rats per group. Formalin induced pain in rats was used to investigate the anti-nociceptive effect of the extract. The extract was administered orally in the treated groups at doses 200, 400, 800 and 1600 mg/kg with aspirin serving as the positive drug control while the normal control group was not given any extract but water. Studies were also carried out on the egg albumin induced antiinflammatory activity in rats by inducing oedema on the left hind paw. The result showed a significant inhibition (p<0.05) on the later phase (800mg/kg) of formalin pain induction in rats; similarly, a significant (p<0.05) anti-inflammatory activity was observed at 60, 90 and 120 minutes. The study thus validates the ethnomedicinal usage of A. difformis in the treatment of pain and inflammation

Control of field- and current-driven magnetic domain wall motion by exchange bias in Cr2 O3/Co/Pt trilayers

We investigate the motion of magnetic domain walls driven by magnetic fields and current-driven spin-orbit torques in an exchange-biased system with perpendicular magnetization. We consider Cr2O3/Co/Pt trilayers as a model system, in which the magnetization of the Co layer can be exchanged biased out-of-plane or in-plane depending on the field-cooling direction. In field-driven experiments, the in-plane exchange bias favors the propagation of the domain walls with internal magnetization parallel to the exchange-bias field. In current-driven experiments, the domain walls propagate along the current direction, but the domain wall velocity increases and decreases symmetrically (antisymmetrically) for both current polarities when the exchange bias is parallel (perpendicular) to the current line. At zero external field, the exchange bias modifies the velocity of current-driven domain wall motion by a factor of 10. We also find that the exchange bias remains stable under external fields up to 15 kOe and nanosecond-long current pulses with current density up to 3.5 × 1012 A/m. Our results demonstrate versatile control of the domain wall motion by exchange bias, which is relevant to achieve field-free switching of the magnetization in perpendicular systems and current-driven manipulation of domain walls velocity in spintronic device

Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus

Merkel cell polyomavirus (MCV) has been recently described as the cause for most human Merkel cell carcinomas. MCV is similar to simian virus 40 (SV40) and encodes a nuclear large T (LT) oncoprotein that is usually mutated to eliminate viral replication among tumor-derived MCV. We identified the hVam6p cytoplasmic protein involved in lysosomal processing as a novel interactor with MCV LT but not SV40 LT. hVam6p binds through its clathrin heavy chain homology domain to a unique region of MCV LT adjacent to the retinoblastoma binding site. MCV LT translocates hVam6p to the nucleus, sequestering it from involvement in lysosomal trafficking. A naturally occurring, tumor-derived mutant LT (MCV350) lacking a nuclear localization signal binds hVam6p but fails to inhibit hVam6p-induced lysosomal clustering. MCV has evolved a novel mechanism to target hVam6p that may contribute to viral uncoating or egress through lysosomal processing during virus replication

Handmade clay bricks: chemical, physical and mechanical properties

The clay brick masonry that is much used in historical structures often is in a rather poor state of conservation. In order to intervene correctly in these buildings, it is convenient to characterize the old material. For this purpose, a large sample of clay brick specimens from the 12th to 19th century were collected from six Portuguese monasteries, and were characterized chemically, physically and mechanically. A large variability of the properties was found. Additionally, a sample of handmade new bricks, which are commonly used as replacing material, was also analysed. The results were compared to the old bricks and could be possibly adequate as substitution bricks. Still, significant differences were found in chemical composition, and in water absorption and porosity, which are much lower in modern handmade bricks. With respect to mechanical properties, the range of values found in old bricks was rather high and the degree of deterioration exhibited a large scatter, meaning that a conclusion is hardly possible.The authors gratefully acknowledge the Instituto de Gestao do Patrimonio Arquitectonico e Arqueologico (IGESPAR) for providing the old clay bricks used in the present work. The first author acknowledges the partial funding of this work by the FCT through the following scholarships POCTI SFRH/BD/6409/2001 and POCTI SFRH/BPD/26706/2005

Detachment analysis of dehumidified repair mortars applied to historical masonry walls

An innovative laboratory procedure for the pre-qualification of repair mortars is described. The tested mortars are suitable for use with new dehumidified plasters applied to historical masonry walls. Long-term plaster detachment frequently occurs because of the mechanical incompatibility of mortar. The procedure consists of the application of static loads to mixed stone block-mortar specimens with particular characteristics, in terms of geometry and adhesion at the interface. A numerical simulation based on the cohesive crack model was used to follow the experimental data, in order to describe the evolutionary phenomenon of detachment as a function of a small number of parameters. The methodology is currently being used at Sacro Monte di Varallo Special Natural Reserve (UNESCO heritage site) in Piedmont (Italy

Lumen-apposing metal stent through the meshes of duodenal metal stents for palliation of malignant jaundice

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard procedure for malignant jaundice palliation; however, it can be challenging when a duodenal self-expandable metal stent (SEMS) is already in place. Patients and methods The primary aim of our study was to evaluate the technical feasibility of the placement of a lumen apposing metal stent (LAMS) through the mesh (TTM) of duodenal stents. The secondary aims were to evaluate clinical outcomes and adverse events (AEs) related to the procedures. Results Data from 23 patients (11 F and 12 M; mean age: 69.5 ± 11 years old) were collected. In 17 patients (73.9 %) TTM LAMS placement was performed as first intention, while in six patients (26.1 %) it was performed after a failed ERCP. Thirteen patients (56.5 %) underwent the procedure due to advanced pancreatic head neoplasia. One technical failure was experienced (4.3 %). The TTM LAMS placement led to a significant decrease in the serum levels of bilirubin, ALP, GGT, WBC and CRP. No cases of duodenal SEMS occlusion occurred and no other AEs were observed during the follow-up. Conclusions Concomitant malignant duodenal and biliary obstruction is a challenging condition. Palliation of jaundice using TTM LAMS in patients already treated with duodenal stent is associated to promising technical and clinical outcomes

Reducing bias in auditory duration reproduction by integrating the reproduced signal

Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

Mutant huntingtin confers cell-autonomous phenotypes on Huntington’s disease iPSC-derived microglia

Huntington’s disease (HD) is a neurodegenerative disorder caused by a dominantly inherited CAG repeat expansion in the huntingtin gene (HTT). Neuroinflammation and microglia have been implicated in HD pathology, however it has been unclear if mutant HTT (mHTT) expression has an adverse cell-autonomous effect on microglial function, or if they are only activated in response to the neurodegenerative brain environment in HD. To establish a human cell model of HD microglia function, we generated isogenic controls for HD patient-derived induced pluripotent stem cells (iPSC) with 109 CAG repeats (Q109). Q109 and isogenic Q22 iPSC, as well as non-isogenic Q60 and Q33 iPSC lines, were differentiated to iPSC-microglia. Our study supports a model of basal microglia dysfunction in HD leading to elevated pro-inflammatory cytokine production together with impaired phagocytosis and endocytosis capacity, in the absence of immune stimulation. These findings are consistent with early microglia activation observed in pre-manifest patients and indicate that mHTT gene expression affects microglia function in a cell-autonomous way

Phase I/II Trial of Liver-derived Mesenchymal Stem Cells in Pediatric Liver-based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver-derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

Background. Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses