Gangliosides, or sialic acid, antagonize ethanol intoxication

Because ethanol elicits a dose-dependent hydrolysis of brain sialogangliosides, we tested the possibility that injected gangliosides might antagonize intoxicating doses of ethanol. Clear anti-intoxication effects were seen at 24 hr post-injection of mixed mouse-brain gangliosides at 125-130 mg/kg, but not at lower or higher doses. Sleep time was reduced on the order of 50%, and roto-rod agility was significantly enhanced. Sialic acid (SA) similarly antagonized ethanol; however, the precursor of SA, N-acetyl-D-mannosamine, as well as ceramide and asialoganglioside did not.     

Trypanosoma lewisi: ultrastructural observations of surface antigen movement induced by antibody.

Cellular antigens of Trypanosoma lewisi have been located with ferritin-conjugated antibody (FCA) at the ultrastructural level. Incubation of live T. lewisi with antibodies from infected rats and ferritin-labeled rabbit anti-rat γ-globulin induced aggregation of surface antigens in the flagellar pockets, the desmosomal regions, and the flagellar membranes of parasites. Aggregation of surface antigens was not observed when the trypanosomes were incubated with γ-globulin and FCA at low temperatures (0–4 C). Sections of trypanosomes incubated at 37 C for 15 or 30 min after incubation at 0 C with FCA showed internalization of FCA in membrane-bound vesicles. Studying the movement and aggregation of these parasites' surface antigens may give information about the molecular dynamics of the plasma membrane and provide insights into the trypanosomes' antigenic modulation and the hosts' immunological responses.     

Structural diversity in two dimensional chiral coordination polymers involving 4,4′-bipyridine and l-cysteate as bridging ligands with Zn and Cd metal centres: Synthesis, characterization and X-ray crystallographic studies

Two chiral coordination polymers involving amino acid backbone l-cysteic acid (H₂l-cys) and N-donor ligand 4,4′-bipyridine (4,4′-bpy) [{Cd(l-cys)(4,4′-bpy)(H₂O)}3.5H₂O]_n1, [{Zn₂(l-cys)₂(4,4′-bpy)₂(H₂O)₄}·(H₂O)·(4,4′-bpy)]_n2 with rectangular grids have been synthesized. Both compounds are insoluble in common polar/non-polar solvents and well characterized by various physico-chemical techniques such as CHN, IR, TGA, NMR, solid state CD and single crystal X-ray diffraction methods. Complexes 1 and 2 comprise l-cysteate dianions self assembled into chiral coordination polymers by bridging the adjacent metal centres through the carboxylate oxygen generating one-dimensional helical chains. The helical chains are pillared by 4,4′-bpy generating two dimensional network. Complex 1 generates two dimensional (4,4) rectangular grid network with dimension 4.77 Å × 11.74 Å (based on d_Cd···Cd) involving with the edge sharing l-cys and 4,4′-bpy ligands, respectively. Complex 2 possesses a brick-wall type (6,3) network topology with edge lengths of the grids 11.42 Å × 10.11 Å based on d_Zn···Zn. Lattice water molecules are encapsulated between the adjacent rectangular grids via hydrogen bonding interactions. One 4,4′-bpy moiety is stacked between the adjacent layers of brick-wall network via weak π···π interaction with the edge sharing N-donor ligand. Even though both the complexes are rigid and stable, N₂ adsorption studies by these complexes revealed not much promising results. The terminal protruding sulphonate groups, angular orientation of the grids within the two-dimensional network and interpenetration of the adjacent offset sheets concomitantly prevent the formation of through tubular channels. Flexible coordination geometry around the metal centre and the versatile coordination mode of the amino carboxylate group from the l-cys moiety are accountable for the variation of the appealing network topology in these complexes. Chiral nature is established by solid state CD spectrum which shows a positive cotton effect for both complexes.     

Plasma Total Nitric Oxide and Endothelial Constitutive Nitric Oxide Synthase (ecNOS) Gene Polymorphism: A Study in a South Indian Population

In an analysis of the possible association of endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphism and plasma nitric oxide levels in patients with acute coronary syndrome, we investigated 106 patients with the syndrome and 100 healthy controls. Genotype was determined using the polymerase chain reaction; plasma nitric oxide levels were found using ELISA. The genotype frequencies for the a/b polymorphism in the control group were 77% for bb, 19% for ab, and 4% for aa. In the patients, genotype frequencies were 55% bb, 34% ab, and 11% aa. The allele frequencies were 28% a and 72% b among the patients and 13% a and 87% b among control subjects. Our findings showed a significant association of the ecNOS gene polymorphism with acute coronary syndrome in the South Indian population.     

Small molecule inhibitors as probes for estrogen and androgen receptor action

Because activated estrogen (ER) and androgen (AR) receptors stimulate cell proliferation in breast and prostate cancer, inhibiting their actions represents a major therapeutic goal. Most efforts to modulate ER and AR activity have focused on inhibiting the synthesis of estrogens or androgens or on the identification of small molecules that act by competing with agonist hormones for binding in the ligand-binding pocket of the receptor. An alternative approach is to implement screens for small molecule inhibitors that target other sites in the pathway of steroid receptor action. Many of these second-site inhibitors directly target ER or AR; others have still unknown sites of action. Small molecule inhibitors that target second sites represent new leads with clinical potential; they serve as novel modulators of receptor action; and they can reveal new and as yet unidentified interactions and pathways that modulate ER and AR action.     

Finger Position Alters the Median Nerve Properties within the Carpal Tunnel: A Pre-Post MRI Comparison Study

Purpose

The purpose of this study was to compare the properties of the median nerve and the flexor retinaculum within the carpal tunnel with Magnetic Resonance Imaging (MRI) under two conditions: (a) fingers extended, and (b) fingers in an isometric squeeze grip.

Methods

Thirty-Four volunteers participated in this experimental study. The flexor retinaculum and median nerve characteristics were measured during both conditions using MRI.

Results

The isometric squeeze grip condition resulted in significant palmar bowing of the flexor retinaculum (t = 7.67, p<.001), a significant flattening-ratio of the median nerve (t = 4.308, p<.001), and no significant decrease in the cross-sectional area of the median nerve (t = 2.508, p = 0.017).

Conclusion

The isometric squeeze grip condition resulted in anatomical deformations within the carpal tunnel, possibly explained by the lumbrical muscles incursion into the carpal tunnel during finger flexion.     

New β-lactam – Tetramic acid hybrids show promising antibacterial activities

β-Lactams are the most important class of antibiotics, for which the emergence of resistance threatens their utility. As such, we explored the extent to which the tetramic acid motif, frequently found in naturally occurring antibiotics, can be used to generate novel β-lactam antibiotics with improved antibacterial activity. We synthesized new ampicillin – tetramic acid, cephalosporin – tetramic acid, and cephamycin – tetramic acid analogs and evaluated their activities against problematic Gram-positive and Gram-negative pathogens. Amongst the analogs, a 7-aminocephalosporanic acid analog, 3397, and a 7-amino-3-vinyl cephalosporanic acid, 3436, showed potent activities against S. aureus NRS 70 (MRSA) with MICs of 6.25?μg/mL and 3.13?μg/mL respectively. These new analogs were ≥16-fold more potent than cefaclor and cephalexin. Additionally, a Δ² cephamycin – tetramic acid analog 3474 which contained a basic guanidinium substituent at the 5-position of the tetramic acid core displayed potent activity against several clinical strains of K. pneumoniae and E. coli.     

Record of Blue tilapia Oreochromis aureus (Steindachner, 1864) in the Eerste River catchment,Western Cape province,South Africa

Oreochromis aureus was imported from Israel into South Africa in 1959 but data on its current status in South Africa are lacking. Genomic DNA was extracted and the COI gene amplified at the South African Institute for Aquatic Biodiversity. The identity of the sequences and specimens was determined using the Barcode of Life Data Systems and GenBank. Morphological and genetic assessment demonstrated that 11 specimens collected from two farm dams in the Eerste River System, Western Cape province, were Oreochromis aureus. A MaxEnt model compiled using global distribution, rainfall and temperature data predicted that large areas of southern Africa were climatically suitable for this species, indicating considerable invasion debt in southern Africa. As a result, surveys to assess for the extent of the invasion in South Africa and eradication of existing populations, if feasible, are recommended management actions.     

Circulating ANGPTL8/Betatrophin Is Increased in Obesity and Reduced after Exercise Training

Objective

ANGPTL8 is a liver and adipose tissue produced protein that regulates the level of triglyceride in plasma as well as glucose homeostasis. This study was designed to evaluate the level of ANGPTL8 in obese and non-obese subjects before and after exercise training.

Methods

A total of 82 non-obese and 62 adult obese were enrolled in this study. Subjects underwent a three months of exercise training. Both full length and C-terminal 139–198 form of ANGPTL8 were measured by ELISA.

Results

Our data show that the full length ANGPTL8 level was increased in obese subjects (1150.04 ± 108.10 pg/mL) compared to non-obese (775.54 ± 46.12) pg/mL (p-Value = 0.002). C-terminal 139–198 form of ANGPTL8 was also increased in obese subjects 0.28 ± 0.04 ng/mL vs 0.20 ± 0.02 ng/mL in non-obese (p-value = 0.058). In obese subjects, the levels of both forms were reduced after three months of exercise training; full length was reduced from 1150.04 ± 108.10 pg/mL to 852.04 ± 51.95 pg/mL (p-Values 0.015) and c-terminal form was reduced from 0.28 ± 0.04 ng/mL to 0.19 ± 0.03 ng/mL (p-Value = 0.058). Interestingly, full length ANGPTL8 was positively associated with fasting blood glucose (FBG) in non-obese (r = 0.317, p-Value = 0.006) and obese subjects (r = 0.346, p-Value = 0.006) C-terminal 139–198 form of ANGPTL8 on the other hand, did not show any correlation in both groups.

Conclusion

In conclusion, our data demonstrate that ANGPTL8 was increased in obesity and reduced after exercise training supporting the potential therapeutic benefit of reducing ANGPTL8. The various forms of ANGPTL8 associated differently with FBG suggesting that they have different roles in glucose homeostasis.