Involvement of ras p2I in Neurotrophin-induced Response of Sensory, but Not Sympathetic Neurons

Little is known about the signal transduction mechanisms involved in the response to neurotrophins and other neurotrophic factors in neurons, beyond the activation of the tyrosine kinase activity of the neurotrophin receptors belonging to the trk family. We have previously shown that the introduction of the oncogene product ras p21 into the cytoplasm of chick embryonic neurons can reproduce the survival and neurite-outgrowth promoting effects of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), and of ciliary neurotrophic factor (CNTF). To assess the potential signal- transducing role of endogenous ras p21, we introduced function-blocking anti-ras antibodies or their Fab fragments into cultured chick embryonic neurons. The BDNF-induced neurite outgrowth in E12 nodose ganglion neurons was reduced to below control levels, and the NGF- induced survival of E9 dorsal root ganglion (DRG) neurons was inhibited in a specific and dose-dependent fashion. Both effects could be reversed by saturating the epitope-binding sites with biologically inactive ras p21 before microinjection. Surprisingly, ras p21 did not promote the survival of NGF-dependent E12 chick sympathetic neurons, and the NGF-induced survival in these cells was not inhibited by the Fab-fragments. The survival effect of CNTF on ras-responsive ciliary neurons could not be blocked by anti-ras Fab fragments. These results indicate an involvement of ras p21 in the signal transduction of neurotrophic factors in sensory, but not sympathetic or ciliary neurons, pointing to the existence of different signaling pathways not only in CNTF-responsive, but also in neurotrophin-responsive neuronal populations

Ras p21 protein promotes survival and fiber outgrowth of cultured embryonic neurons

Although evidence obtained with the PC12 cell line has suggested a role for the ras oncogene proteins in the signal transduction of nerve growth factor-mediated fiber outgrowth, little is known about the signal transduction mechanisms involved in the neuronal response to neurotrophic factors in nontransformed cells. We report here that the oncogene protein T24-ras, when introduced into the cytoplasm of freshly dissociated chick embryonic neurons, promotes the in vitro survival and neurite outgrowth of nerve growth factor-responsive dorsal root ganglion neurons, brain-derived neurotrophic factor-responsive nodose ganglion neurons, and ciliary neuronotrophic factor-responsive ciliary ganglion neurons. The proto-oncogene product c-Ha-ras also promotes neuronal survival, albeit less strongly. No effect could be observed with truncated counterparts of T24-ras and c-Ha-ras lacking the 23 C-terminal amino acids including the membrane-anchoring, palmityl-accepting cysteine. These results suggest a generalized involvement of ras or ras-like proteins in the intracellular signal transduction pathway for neurotrophic factors

Investigation of phosphatases in Ascaridia galli, A Bird Nematode parasite

Phosphates play an important role in metabolic activities especially in carbohydrate metabolism. The phosphatases constitute a large group of enzymes that are involved in many important phases of intermediary metabolism. They are differentiated into three types i.e. A) pyrophosphatases (inorganic and organic) B) phosphomonoesterases C) phosphodiesterases. Depending upon the substrates that are singly or doubly esterified phosphatates to which these are specific, respectively. These group, in turn, has two sub groups one of low and the other of high specificity. The phosphomonoesterases of low specificity will have optimum activity either in the acid or alkaline range, depending upon which these can be acid or alkaline phosphatases which is recovered from Ascaridia galli Schrank  [5] from Nanded region (M.S.) India

Status of cholesterol and lipase in Ascaridia galli nematode parasite parasitizing Domestic Fowl Host

In A. galli Schrank [17], Freeborn, [8] most of the lipids are located in the hypodermis, especially in the lateral cords, in the non-contractile part of the muscle cells, in the intestine of host. Cholesterol and lipase has a variety of functions in tissues. Cholesterol occurs in association with proteins, carbohydrates, lipo proteins and glycolipids. They are major structural components of cell membranes. Lipids include simple lipids, such as fats and oils and derived lipids such as fatty acids, cholesterol and ketone bodies

Effect of nicotine on serotonin (5-HT) levels in brain of depressed rats

Background: Reduction in brain serotonin (5-HT) levels contributes to depression. Nicotine may have antidepressant properties and smokers self-medicate underlying depression. Epidemiological findings suggest that smokers more often demonstrate depressive symptoms than non-smokers and depressed patients are less likely to cease smoking. Therefore, the study was planned to evaluate the effect of nicotine on serotonin levels in brain of depressed rats.Methods: Antidepressant action of study drugs was evaluated using isolation induced hyperactivity model in rats. Rats were divided into five groups with six rats in each group. Study groups: Vehicle in normal rats 1 ml/kg (subcutaneous); vehicle after isolation 1ml/kg (subcutaneous); imipramine 10 mg/kg (intraperitoneal) for 7 consecutive days; single dose of nicotine 0.4 mg/kg (subcutaneous); single dose of nicotine 0.2 mg/kg (inhalational). Brain serotonin assay was carried out. The statistical significance was determined by ANOVA followed by Tukey test (p<0.05).Results: Serotonin levels (55.93ng/g of brain tissue) in rats after isolation were significantly less than in normal rats (335.87ng/g) (p<0.001). In imipramine treated group, serotonin levels (301.4ng/g) after isolation were highly significant as compared to serotonin levels in vehicle treated group after isolation (p<0.001). Nicotine administered by subcutaneous and inhalational route showed significantly higher brain serotonin levels, i.e. 175ng/g and 254.62ng/g respectively as compared to vehicle treated rats after isolation (p<0.001).Conclusions: Single dose nicotine (inhalational) produced significant antidepressant action comparable to that of seven days’ treatment of standard antidepressant drug imipramine in rats. In rats, nicotine by both routes i.e. subcutaneous and inhalational increased serotonergic activity

Therapeutic approaches to drug targets in atherosclerosis

AbstractNon-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis

Synthesis, Characterization, and Biological Evaluation of certain 6-methyl-2(3H)-benzo-1, 3-thiazolyl-1’-ethylidene-2-(o, p- Substituted Acetophenones) Hydrazine Analogs

In the present study, five new derivatives (GG4 to GG8) of benzothiazoles were synthesized and evaluated against Staphylococcus aureus (MTCC 737), Pseudomonas aeruginosa (MTCC 424), Escherichia coli (MTCC 1687), and yeast-like fungi Candida tropicalis. p-Toluidine on treatment with ammonium thiocynate formed 2-benzothiazolamines (II), which on reaction with hydrazine hydrate formed a hydrazino derivative (III). Compounds GG4 to GG8 were synthesized by reacting the hydrazine derivative with different acetophenones. All the synthesized compounds were identified by IR and 1H-NMR, and antimicrobial activity was performed on the synthesized compounds. Presence of NO2, Br, OCH3, and Cl groups to the substituted benzothiazole enhanced the antibacterial and antifungal activities

Distribution and abundance of freshwater snails in Warwade Dam, Dutse, Northern Nigeria

Preliminary investigation in August, 2017 reported the presence of Lymnaea natalensis, Bellamya unicolor, Melanoides tuberculata and Bulinus globosus in order of increasing abundance and distribution in Warwade dam, Dutse, Jigawa State, Nigeria. A follow up study was carried out from April to October, 2019 to reveal further details on the abundance and distribution of freshwater snails in relation to some physiochemical factors of the dam. Four sampling sites; human activity, vegetation cover, lentic and lotic were selected for the study along the bank of the dam. Freshwater snails were collected using long handled scoop net with mesh 0.2mm complemented by hand picking methods in the four sampling sites. Water samples from the sampling sites were analyzed in the laboratory using standard procedures. A total of 2,027 of freshwater snails belonging to ten species were identified. Bulinus globosus 12(0.6%) and Lymnaea natalensis 12(0.6%) had the lowest abundance and distribution while Melanoides tuberculata 1553(76.6%) had the highest. Snail abundance was highest in site characterized by human activities (670) followed by vegetation (482), lotic (442) and lentic (433) waters. Most of the physico-chemical factors measured appeared to favour the growth and survival of fresh water snails. pH (p = 0.01), water current (p = &lt;0.01) and magnesium ion concentration (p = &lt; 0.01) varied significantly across the four sites. Only calcium ion concentration was significantly associated with snail abundance (p = 0.04). Snail abundance showed weak positive relationship with water temperature, color, turbidity and concentration of magnesium ion. The dam habours about ten species of freshwater snails in different abundance and distribution with M. tuberculata being the most abundant throughout the period of investigation. The dominance of M. tuberculata over other species particularly those of medical and veterinary importance could have positive implication for their control in the dam

Adventive hydrothermal circulation on Stromboli volcano (Aeolian Islands, Italy) revealed by geophysical and geochemical approaches: Implications for general fluid flow models on volcanoes

International audienceOn March 15th 2007 a paroxysmal explosion occurred at the Stromboli volcano. This event generated a large amount of products, mostly lithic blocks, some of which impacted the ground as far as down to 200 m a.s.l., about 1.5 km far away from the active vents. Two days after the explosion, a new vapour emission was discovered on the north-eastern flank of the volcanic edifice, at 560 m a.s.l., just above the area called "Nel Cannestrà". This new vapour emission was due to a block impact. In order to investigate the block impact area to understand the appearance of the vapour emission, we conducted on May 2008 a multidisciplinary study involving Electrical Resistivity Tomography (ERT), Ground Penetrating Radar (GPR), Self-Potential (SP), CO2 soil diffuse degassing and soil temperature surveys. This complementary data set revealed the presence of an anomalous conductive body, probably related to a shallow hydrothermal level, at about 10-15 m depth, more or less parallel to the topography. It is the first time that such a hydrothermal fluid flow, with a temperature close to the water boiling point (76 °C) has been evidenced at Stromboli at this low elevation on the flank of the edifice. The ERT results suggest a possible link between (1) the main central hydrothermal system of Stromboli, located just above the plumbing system feeding the active vents, with a maximum of subsurface soil temperature close to 90 °C and limited by the NeoStromboli summit crater boundary and (2) the investigated area of Nel Cannestrà, at ~ 500 m a.s.l., a buried eruptive fissure active 9 ka ago. In parallel, SP and CO2 soil diffuse degassing measurements suggest in this sector at slightly lower elevation from the block impact crater a magmatic and hydrothermal fluid rising system along the N41° regional fault. A complementary ERT profile, on May 2009, carried out from the NeoStromboli crater boundary down to the block impact crater displayed a flank fluid flow apparently connected to a deeper system. The concept of shallow hydrothermal level have been compared to similar ERT results recently obtained on Mount Etna and La Fossa cone of Vulcano. This information needs to be taken into account in general fluid flow models on volcanoes. In particular, peripheral thermal waters (as those bordering the north-eastern coast of Stromboli) could be contaminated by hydrothermal and magmatic fluids coming from regional faults but also from the summit

New perspectives in human stem cell therapeutic research

Human stem cells are in evaluation in clinical stem cell trials, primarily as autologous bone marrow studies, autologous and allogenic mesenchymal stem cell trials, and some allogenic neural stem cell transplantation projects. Safety and efficacy are being addressed for a number of disease state applications. There is considerable data supporting safety of bone marrow and mesenchymal stem cell transplants but the efficacy data are variable and of mixed benefit. Mechanisms of action of many of these cells are unknown and this raises the concern of unpredictable results in the future. Nevertheless there is considerable optimism that immune suppression and anti-inflammatory properties of mesenchymal stem cells will be of benefit for many conditions such as graft versus host disease, solid organ transplants and pulmonary fibrosis. Where bone marrow and mesenchymal stem cells are being studied for heart disease, stroke and other neurodegenerative disorders, again progress is mixed and mostly without significant benefit. However, correction of multiple sclerosis, at least in the short term is encouraging. Clinical trials on the use of embryonic stem cell derivatives for spinal injury and macular degeneration are beginning and a raft of other clinical trials can be expected soon, for example, the use of neural stem cells for killing inoperable glioma and embryonic stem cells for regenerating β islet cells for diabetes. The change in attitude to embryonic stem cell research with the incoming Obama administration heralds a new co-operative environment for study and evaluation of stem cell therapies. The Californian stem cell initiative (California Institute for Regenerative Medicine) has engendered global collaboration for this new medicine that will now also be supported by the US Federal Government. The active participation of governments, academia, biotechnology, pharmaceutical companies, and private investment is a powerful consortium for advances in health