Basal and Experience Dependent Ampar and Synapse Dynamics: Alterations in a Mouse Model of Fragile X Syndrome

Dendritic spines are the principal sites of excitatory synapses in the neurons of mammalian central nervous system. Spine are plastic, undergoing structural and functional changes under basal and experience dependent conditions. Spine properties are altered in a number of neurodevelopmental disorders including the Fragile X syndrome (FXS) which is the most common inherited form of intellectual disability. The structural reorganization of dendritic spines is thought to be associated with synaptic plasticity mechanisms that are deficient in FXS. A number of synaptic plasticity mechanisms involve modulation of synaptic strength via insertion or removal of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). However, the link between synaptic behavior and AMPAR dynamics has not been previously studied in vivo. To investigate the role of AMPAR in spine dynamics in vivo we expressed AMPAR subunit GluA2 tagged to superecliptic phluorin (SEP), a pH sensitive GFP variant, in layer 2/3 neurons of the primary motor cortex (M1). Dendritic spines and sGluA2 were imaged in vivo using two-photon light microscopy over a period of ten days in both wild type and the fmr1 knock out (KO) mice, a mouse model of FXS. Repeated in vivo imaging revealed that in the fmr1 KO mouse dendritic spines were denser, smaller, contained less sGluA2 and had higher turnover rates compared to littermate controls (WT). Our data confirmed the relationship between synaptic strength and synaptic stability, with greater AMPAR containing spines being more stable in both WT and the KO mice. Additionally, we observed that AMPAR levels were dynamic in most stable spines, fluctuating over 10 days with larger proportion of spines showing multiple dynamic events of AMPAR in the KO. Directional changes in sGluA2 were also observed in subpopulation of spines, with new small spines gradually accumulating sGluA2. Moreover, sGluA2 levels dropped just prior to spine elimination with greater loss observed in the KO spines. To further investigate the role of AMPAR in experience dependent plasticity, we trained KO mice in a forelimb task and monitored behavioral learning and biochemically measured synaptic AMPAR levels. KO mice had mild motor deficits in a single forelimb reaching task compared to WT controls. Furthermore, after one day of motor skill training WT mice had a gradual increase in synaptic sGluA1 which was delayed in the KO. Thus we conclude that AMPAR levels within spines are continuously dynamic and are predictive of spine behavior. These dynamics are further modulated upon learning with impairments under basal and experience dependent conditions in the fmr1 KO mouse

Two cases of Salmonella breast abscess in pregnancy: a diagnostic challenge

Breast abscess in pregnancy due to Salmonella has been very rarely reported in the literature and most of the cases till now are due to unknown risk factors or in otherwise immunocompromised adults. Localized disease can occur due to bacteremia followed by seeding of bacteria at distant sites. We report two cases of breast abscess in pregnancy cause by Salmonella typhi where drainage of abscess and appropriate antibiotics helped in complete resolution

A giant submandibular sialolith - How to manage?

The presence of a sialolith is one of the most common diseases of salivary gland. It is relatively common in submandibular salivary glands and its duct. This case report is of a patient who presented at our unit with a history of severe pain and swelling on floor of the mouth, which was clinically and radiographically diagnosed as a sialolith. The diagnostic and treatment protocol in managing a patient with a giant sialolith is enumerated in this manuscript

Serum Electrophoretic Changes in Patients with Pulmonary Tuberculosis, Chronic Bronchitis, Bronchiectasis, and Asthma

Patients with multiple myeloma, Hodgkin\u27s disease and other lymphomas have gamma globulin peaks in their serum electrophoretic pattern much above normal; usually, they also have histories of repeated infections, as well as poor antibody response to specific antigens. High serum gamma globulin levels have been noted by some investigators in patients with a variety of diseases associated with chronic infections—including certain chest diseases. The present study consisting of 254 patients and forty-one controls, showed a statistically significant elevation of the serum gamma globulin levels in patients with tuberculosis (active or inactive), bronchiectasis chronic bronchitis, and the infectious type of asthma. On the other hand, patients with allergic asthma or with mixed-type asthma had gamma globulin levels within the normal range. Since some of the patient subjects had high serum gamma globulin levels, it was hypothesized that they might show (as do patients with multiple myeloma, Hodgkin\u27s disease, and other lymphomas) poor antibody response to specific antigens. In order to test this hypothesis, a controlled study was undertaken in which eleven patients with chronic bronchitis and a history in common of repeated respiratory infections and five \u22normal control subjects\u22 were immunized with diphtheria toxoid, staphage lysate, mumps, influenza, and typhoid-paratyphoid vaccines. Although incomplete, the results obtained from this small series of patients suggest that a factor other than antibody response seems to play an important role in the increased susceptibility of these patients to infections

Targeting groundwater potential zones using Electrical resistivity and GIS techniques in Kadavanar Sub-basin, South India

Geographical Information System techniques are widely used to determine suitable sites for groundwater recharge through artificial recharge techniques. The present research work is to identify suitable locations for constructing artificial recharge structures in the Kadavanar Sub-basin, South India. People in the Sub-basin mainly depend on the groundwater resources for drinking and irrigation purposes. Groundwater resources are often overexploited in many parts of this Sub-basin to meet the water demand leading to groundwater consumption. A lot of surfaces and sub-surface information and criteria are required for mapping the groundwater recharge zone. This is where the geographic information system [GIS] provides the right impetus besides the groundwater prospective zone to harness multilayered spatial data so that multi-criteria analysis is possible. This analysis integrates historic rainfall data analysis, groundwater level fluctuation, stream network, aquifer thickness, land use/land cover and basin slope. Drainage map, slope map and land use/land cover maps were prepared from satellite imageries. Vertical electrical sounding (VES) geophysical survey with Schlumberger electrode configuration was also conducted in the basin at 50 locations to map the aquifer thickness. Spatial variation maps for groundwater level and aquifer thickness were generated using GIS. Weighted aggregation method was used in this study to obtain groundwater recharge maps. Finally, multi-criteria analysis has been carried out to identify and assess the potential sites for groundwater recharge according to the associated weightages. It is established that GIS is best suited for the mapping of groundwater recharge zones. A similar study can be extended to any other hard-rock region facing water crises

Pharmacological role of atorvastatin in myocardium and smooth muscle progenitor cells

Atorvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor with a great potency in the reduction of lipids and it has been well documented in both primary and secondary prevention studies. It exhibits pleiotropic properties in both in-vitro and in vivo conditions. Conversely, atorvastatin remain under-utilized in several situations. The main objective of this review is to focuses the pharmacological benefits, pleiotropic properties of the atorvastatin related to smooth muscle proliferation and myocardium

Evaluation of coronary artery risk factors in premenopausal women (

Background: The present study was designed to evaluate the association of conventional coronary risk factors in the angiographically proven cases of younger women (<45 years) with significant CAD along with clinical profile and coronary angiographic findings.Methods: This was a hospital-based prospective study conducted at a tertiary-care center in India. A total of 200 premenopausal women (age ≤45 years) who presented with chest pain likely to be of cardiac origin were enrolled. Each patient was subjected to routine clinical investigations, examination of complete lipid profile, follicular stimulating hormone (FSH), luteinizing hormone (LH), and prolactin; and underwent non-invasive cardiac examination and coronary angiography.Results: Mean age of patients was 39.1±4.98 years. A total of 64 (32%) patients had history of spontaneous abortions and 80 (40%) patients presented with ST-elevated myocardial infarction. Increased FSH, LH and prolactin levels was found in 70 (35%), 20 (10%), and 88 (44%) patients, respectively. Total 196 (98%) patients underwent coronary angiography which revealed presence of significant CAD in 122 (63%) cases and of which 80 patients underwent coronary angioplasty and 12 underwent coronary artery bypass grafting. Of all, 8 death were reported up to the mean follow-up of 11 months.Conclusions: The study stated that premenopausal females (<45 years) represent a special subgroup where non-conventional risk factors play an important role in occurrence of CAD. So, careful history taking with detailed menstrual and obstetric history should be considered in such group of patients

Vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) in Amyotrophic Lateral Sclerosis (ALS) patients

Correction to Gupta P K, Prabhakar S, Sharma S, Anand A. Vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) in amyotrophic lateral sclerosis (ALS) patients. Journal of Neuroinflammation 8:47