Calcium-binding proteins in chemoreceptors of Xenopus laevis.

Calcium-binding proteins were investigated immunohistochemically in chemo-receptors of the olfactory epithelium and taste buds of the clawed frog, Xenopus laevis. Calmodulin-, S-100- and calbindin-immunoreactive material were found in sensory cells of the olfactory epithelium; however, parvalbumin-like material was absent in these cells. Taste buds of the palate showed calmodulin-, S-100- and parvalbumin-immunoreactive material in sensory cells, while calbindin-immunoreactive material in supporting cells. Merkel cells, surrounding the base of the taste buds in a ring-like manner, exhibited calmodulin- and S-100-immunoreactive material.     

Rosuvastatin protects isolated hearts against ischemia-reperfusion injury: role of Akt-GSK-3β, metabolic environment,and mitochondrial permeability transition pore

Journal of Physiology and Biochemistry - The cardioprotective activity of rosuvastatin (R) is yet to be known. The objective of this study was to research whether R perfusion before global ischemia...     

Four millennia of vegetation and environmental history above the Hyrcanian forest,northern Iran

Vegetation History and Archaeobotany - Past vegetation, fire, and climate dynamics, as well as human impact, have been reconstructed for the first time in the highlands of the Gilan province in the...     

Intensification of agriculture in southwestern Germany between the Bronze Age and Medieval period,based on archaeobotanical data from Baden-Württemberg

Vegetation History and Archaeobotany - A system of farming with an alternation of land use between being cultivated or left fallow as grassland (Feldgraswirtschaft) developed in southwestern...     

Critical considerations for the development of potency tests for therapeutic applications of mesenchymal stromal cell-derived small extracellular vesicles

Mesenchymal stromal/stem cells (MSCs) have been widely tested against many diseases, with more than 1000 registered clinical trials worldwide. Despite many setbacks, MSCs have been approved for the treatment of graft-versus-host disease and Crohn disease. However, it is increasingly clear that MSCs exert their therapeutic functions in a paracrine manner through the secretion of small extracellular vesicles (sEVs) of 50–200 nm in diameter. Unlike living cells that can persist long-term, sEVs are non-living and non-replicative and have a transient presence in the body. Their small size also renders sEV preparations highly amenable to sterilization by filtration. Together, acellular MSC-sEV preparations are potentially safer and easier to translate into the clinic than cellular MSC products. Nevertheless, there are inherent challenges in the development of MSC-sEV drug products. MSC-sEVs are products of living cells, and living cells are sensitive to changes in the external microenvironment. Consequently, quality control metrics to measure key identity and potency features of MSC-sEV preparations have to be specified during development of MSC-sEV therapeutics. The authors have previously described quantifiable assays to define the identity of MSC-sEVs. Here the authors discuss requirements for prospective potency assays to predict the therapeutic effectiveness of the drug substance in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. Although potency assays should ideally reflect the mechanism of action (MoA), this is challenging because the MoA for the reported efficacy of MSC-sEV preparations against multiple diseases of diverse underlying pathology is likely to be complex and different for each disease and difficult to fully elucidate. Nevertheless, robust potency assays could be developed by identifying the EV attribute most relevant to the intended biological activity in EV-mediated therapy and quantifying the EV attribute. Specifically, the authors highlight challenges and mitigation measures to enhance the manufacture of consistent and reproducibly potent sEV preparations, to identify and select the appropriate EV attribute for potency assays despite a complex “work-in-progress” MoA and to develop assays likely to be compliant with regulatory guidance for assay validation.     

Effect of Non-Volatile Constituents of Elsholtzia ciliata (Thunb.) Hyl. from Southern Vietnam on Reactive Oxygen Species and Nitric Oxide Release in Macrophages

The extract of Elsholtzia ciliata aerial parts was subjected to bio-guided isolation using the intercellular ROS reduction in J774A.1 macrophages to monitor the anti-oxidative activity. Fifteen compounds were isolated from the active fractions including eleven flavonoids (vitexin, pedalin, luteolin-7-O-β-d -glucopyranoside, apigenin-5-O-β-d -glucopyranoside, apigenin-7-O-β-d -glucopyranoside, chrysoeriol-7-O-β-d -glucopyranoside, 7,3′-dimethoxyluteolin-6-O-β-d -glucopyranoside, luteolin, 5,6,4′-trihydroxy-7,3′-dimethoxyflavone, 5-hydroxy-6,7-dimethoxyflavone (compound 13 ), 5-hydroxy-7,8-dimethoxyflavone); three hydroxycinnamic acid derivatives (caffeic acid, 4-(E)-caffeoyl-l -threonic acid, 4-O-(E)-p-coumaroyl-l -threonic acid) and one fatty acid (α-linolenic acid). The biological evaluation of these compounds (10–2.5 μm ) indicated that all of them exerted good antioxidant and anti-inflammatory activities, in particular compound 13 .     

Intestinal helminths as predictors of some malaria clinical outcomes and IL-1β levels in outpatients attending two public hospitals in Bamenda,North West Cameroon

This study aimed at determining the impact of intestinal helminths on malaria parasitaemia, anaemia and pyrexia considering the levels of IL-1β among outpatients in Bamenda. A cohort of 358 consented participants aged three (3) years and above, both males and females on malaria consultation were recruited in the study. At enrolment, patients’ axillary body temperatures were measured and recorded. Venous blood was collected for haemoglobin concentration and malaria parasitaemia determination. Blood plasma was used to measure human IL-1β levels using Human ELISA Kit. The Kato-Katz technique was used to process stool samples. Five species of intestinal helminths Ascaris lumbricoides (6.4%), Enterobius vermicularis (5.0%), Taenia species (4.2%), Trichuris trichiura (1.1%) and hookworms (0.8%) were identified. The overall prevalence of Plasmodium falciparum and intestinal helminths was 30.4% (109/358) and 17.6% (63/358) respectively. The prevalence of intestinal helminths in malaria patients was 17.4% (19/109). Higher Geometric mean parasite density (GMPD ±SD) (malaria parasitaemia) was significantly observed in patients co-infected with Enterobius vermicularis (5548 ± 2829/μL, p = 0.041) and with Taenia species (6799 ± 4584/μL, p = 0.020) than in Plasmodium falciparum infected patients alone (651 ± 6076/ μL). Higher parasitaemia of (1393 ± 3031/μL) and (3464 ± 2828/μL) were recorded in patients co-infected with Ascaris lumbricoides and with hookworms respectively but the differences were not significant (p > 0.05). Anaemia and pyrexia prevalence was 27.1% (97/358) and 33.5% (120/358) respectively. Malaria patients co-infected with Enterobius vermicularis and Ascaris lumbricoides had increased risk of anaemia (OR = 13.712, p = 0.002 and OR = 16.969, p = 0.014) respectively and pyrexia (OR = 18.07, p = 0.001 and OR = 22.560, p = 0.007) respectively than their counterparts. Increased levels of IL-1β were significantly observed in anaemic (148.884 ± 36.073 pg/mL, t = 7.411, p = 0.000) and pyretic (127.737 ± 50.322 pg/mL, t = 5.028, p = 0.000) patients than in non-anaemic (64.335 ± 38.995pg/mL) and apyretic patients (58.479 ± 36.194pg/mL). Malaria patients co-infected with each species of intestinal helminths recorded higher IL-1β levels (IL-1β > 121.68 ± 58.86 pg/mL) and the overall mean (139.63 ± 38.33pg/mL) was higher compared with levels in malaria (121.68 ± 58.86 pg/mL) and helminth (61.78 ± 31.69pg/mL) infected patients alone. Intestinal helminths exacerbated the clinical outcomes of malaria in the patients and increased levels of IL-1β were observed in co-infected patients with anaemia, pyrexia and higher parasitaemia.     

Performance tradeoffs of energy-aware virtual machine consolidation

Increasing power consumption of IT infrastructures and growing electricity prices have led to the development of several energy-saving techniques in the last couple of years. Virtualization and consolidation of services is one of the key technologies in data centers to reduce overprovisioning and therefore increase energy savings. This paper shows that the energy-optimal allocation of virtualized services in a heterogeneous server infrastructure is NP-hard and can be modeled as a variant of the multidimensional vector packing problem. Furthermore, it proposes a model to predict the performance degradation of a service when it is consolidated with other services. The model allows considering the tradeoff between power consumption and service performance during service allocation. Finally, the paper presents two heuristics that approximate the energy-optimal and performance-aware resource allocation problem and shows that the allocations determined by the proposed heuristics are more energy-efficient than the widely applied maximum-density consolidation.     

Imbricaric Acid and Perlatolic Acid: Multi-Targeting Anti-Inflammatory Depsides from Cetrelia monachorum

In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E₂ synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E₂ synthase-1 (IC₅₀ = 1.9 and 0.4 µM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC₅₀ = 5.3 and 1.8 µM, resp.) and on purified enzyme (IC₅₀ = 3.5 and 0.4 µM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC₅₀ values of 2.0 and 7.0 µM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy.