TNF-α G-308A genetic variants,serum CRP-hs concentration and DNA damage in obese women

Molecular Biology Reports - Obesity is associated with inflammation, which can disturb genome stability. Tumor necrosis factor (TNF-α) polymorphism was found to affect TNF-α protein...     

Synthesis of 27-Oxo, 27-Hydroxymilbemycins A3 and A4 and Novel 27-Alkoxymilbemycins A3 and A4 from Milbemycins A3 and A4 and…

27-Oxomilbemycins A₃ and A₄ and 27-hydroxymilbemycins A₃ and A₄ were identified as metabolites in soil metabolism studies of milbemycins A₃ and A₄. Chemical derivation methods were developed to synthesize 27-oxomilbemycins A₃ and A₄ and 27-hydroxymilbemycins A₃ and A₄ from milbemycins A₃ and A₄. In addition, 27-alkoxymilbemycin derivatives were also synthesized from the same precursors. Some of the synthesized compounds displayed satisfactory acaricidal activity against the organophosphorus-sensitive two-spotted spider mite (Tetranychus urticae), but did not have superior activity to corresponding milbemycins A₃ and A₄.     

Purification and functional analysis of protein kinase G-1α using a bacterial expression system

3',5' Cyclic guanosine monophosphate (cGMP)-dependent protein kinase G-1α (PKG-1α) is an enzyme that is a target of several anti-hypertensive and erectile dysfunction drugs. Binding of cGMP to PKG-1α produces a conformational change that leads to enzyme activation. Activated PKG-1α performs important roles both in blood vessel vasodilation and in maintaining the smooth muscle cell in a differentiated contractile state. Recombinant PKG-1α has been expressed and purified using Sf9-insect cells. However, attempts at purifying full length protein in a soluble and active form in prokaryotes have thus far been unsuccessful. These attempts have been hampered by the lack of proper eukaryotic protein folding machinery in bacteria. In this study, we report the successful expression and purification of PKG-1α using a genetically engineered Escherichia coli strain, Rosetta-gami 2(DE3), transduced with full-length human PKG-1α cDNA containing a C-terminal histidine tag. PKG-1α was purified to homogeneity using sequential nickel affinity chromatography, gel filtration and ion exchange MonoQ columns. Protein identity was confirmed by immunoblot analysis. N-terminal sequencing using Edman degradation demonstrated that the purified protein was full length. Analysis of enzyme kinetics, using a nonlinear regression curve, identified that, at constant cGMP levels (10μM) and varying ATP concentrations, PKG-1α had a maximal velocity (V(max)) of 5.02±0.25pmol/min/μg and a Michaelis-Menten constant (K(m)) of 11.78±2.68μM ATP. Recent studies have suggested that endothelial function can be attenuated by oxidative and/or nitrosative stress but the role of PKG-1α under these conditions is unclear. We found that PKG-1α enzyme activity was attenuated by exposure to the NO donor, spermine NONOate, hydrogen peroxide, and peroxynitrite but not by superoxide, suggesting that the attenuation of PKG-1α activity may be an under-appreciated mechanism underlying the development of endothelial dysfunction in a number of cardiovascular diseases.     

Porcineβ-lactoglobulin A and C

Summary The occurrence of the dominant ‘whey’ protein in samples of milk from 1180 sows is examined. It exhibits genetic polymorphism with some unusual features. Although immunologically different from bovine β-lactoglobulin, it is shown by chemical studies of the isolated protein to be a β-lactoglobulin. Two homozygous genetic variants, designated porcine β-lactoglobulin A and C, are isolated and their amino acid compositions and peptide maps compared. It is shown that the C variant has +1 His, −1 Gln, and +1 Asp, −1 Glu, with respect to the A variant. These variants, containingca. 162 residues per molecule, are considered in relationship to porcine β-lactoglobulins isolated by other workers. The sequence of the first 50 residues is determined and compared with sequence of the bovine protein. The sequences ofca. 70% of the remaining residues is proposed on the basis of the composition of tryptic peptides and assumed homology.     

Insects and packaging — A review

This paper reviews the interactions of insects with food packaging, and measures which may be taken to limit damage.     

The elution patterns of formaldehyde,glutaraldehyde, glyoxal and α-hydroxyadipaldehyde from Sephadex G-10 and their significance for tissue fixation

Summary The following aldehydes were subjected to gel filtration on Sephadex G-10 with 0.2 M phosphate at pH 7.2 as eluant: formaldehyde, glutaraldehyde, glyoxal, and -hydroxyadipaldehyde. Adsorption to the gel was marked with glutaraldehyde, partial with -hydroxyadipaldehyde and glyoxal, and absent with formaldehyde. Commercial -hydroxyadipaldehyde contained various polymers and ultraviolet absorbing impurities. There was little change in optical density with temperature. The relative elution volume was slightly pH sensitive between pH 5.0–8.0. — The significance of these findings to fixation is discussed.     

Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women

Background

Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels.

Methods

The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91 ± 6.05) and 272 healthy females without metabolic syndrome (age 30.96 ± 7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion.

Results

Homozygous mutant genotype (AA) (p = <0.001: OR = 3.24: 95% CI = 2.15-4.89) and mutant allele (A) (p = <0.001: OR = 3.04: 95% CI = 2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors.

Conclusions

Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.     

植物染色体高分辨G-带技术研究

本文对植物染色体高分辨 G-带技术进行了比较系统的研究,并首次运用改良的尿素法在野生一粒小麦、玉米、蚕豆、吊兰、川百合等多种植物上诱导出 G-带,带纹清晰,数目多,分布在染色体全长上。前期染色体带呈颗粒状,中期染色体呈明显带状,与哺乳动物染色体 G-带很相似。G-带的数目取决于染色体浓缩程度,中期染色体一条深带到晚前期可显示出2.67条亚带。作者同时比较了胰酶法与尿素法的显带效果。认为两种方法显示的带纹基本相同,尿素法比胰酶法作用温和,显带时间长达数分钟,易于掌握,重复性高,具有更高的应用价值。     

Hypertension and Diabetes—A Toxic Combination

ObjectiveTo assess the relationship of diabetes and hypertension and the effect on cardiovascular outcomes.MethodsA review of the English-language literature regarding the effects of diabetes and hypertension published between January 1, 1980, and April 30, 2008, was performed.ResultsIn type 2 diabetes, the prevalence of hypertension due to both hyperglycemia and insulin resistance is increased. High insulin levels are associated with left ventricular hypertrophy and decreased ventricular function. The growth factor effects of insulin on the myocardium are worsened by hypertension. The diabetic hypertensive patient is exquisitely sensitive to blood pressure lowering as it relates to cardiac events and mortality. Because of this, the blood pressure goals for diabetic hypertensive patients are lower than those for their nondiabetic hypertensive peers. Cardiac events have a stronger association with systolic hypertension and the pulse pressure than with diastolic hypertension. The presence of microalbuminuria not only signifies a higher risk of developing diabetic nephropathy, but also increased mortality and incidence of cardiovascular events. Thus, when microalbuminuria is detected, intensification of hypertensive therapies, especially suppression of the renin-angiotensin-aldosterone system, is essential.ConclusionThe effects of hypertension in persons with diabetes increase the frequency and severity of cardiac events, especially when microalbuminuria is present. (Endocr Pract. 2008;14:1031-1039)     

Bombing and Sonoran Pronghorn: A Clear and Present Danger?

ABSTRACT The United States Air Force (USAF) uses part of Sonoran pronghorn (Antilocapra americana sonoriensis) habitat for bombing exercises (i.e., Barry M. Goldwater Air Force Range [BMGR], southwest AZ, USA) that could be detrimental to the endangered subspecies. To minimize injury or death to Sonoran pronghorn, the USAF and United States Fish and Wildlife Service developed a monitoring protocol that would eliminate live ordnance delivery in the vicinity of pronghorn. From 1998 to 2003, we searched for pronghorn on or near military targets prior to ordnance delivery. If we observed pronghorn within 5 km of a target, the target was closed for ≥24 hours. We monitored bombing ranges on BMGR and closed >5,000 targets for >1,000 days due to military activity. To our knowledge, no pronghorn were killed or injured. We recommend that the monitoring program continue as long as military activity occurs in pronghorn habitat.     

植物染色体G-带的初步研究

本文首次报道了川百台(Lilium davidii)、华山松(Pinus armardii)和七叶一枝花(Paris polyphylla)等植物染色体G-带研究结果。本试验的G-带与以往的C-带不同,C-带每条染色体上一般只有1-4条带,多分布在着丝点附近,而G-带则多达几十条,分布在整条染色体上,带纹清晰,前期染色体带呈颗粒状,中期染色体呈明显的带状,与哺乳动物染色体G-带很相似。G-带的数目取决于染色体浓缩的程度。前期染色体带纹数目是中期的三倍,接近人类高分辨带水平。对G-带带纹采用了自动光谱分析,波峰数值与带纹相符。作者同时介绍了胰酶法在植物染色体G-带中的应用。认为此方法既适合动物亦适用于植物。但植物G-带显示的关键可能不在胰酶法本身,而在合适的分裂时期及染色体处理技术。     

Adenosine A₂A and A₂B receptors are both required for adenosine A₁ receptor-mediated cardioprotection

All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires the activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine A(2A) and/or A(2B) receptors modulate adenosine A(1) receptor-mediated cardioprotection. Isolated perfused hearts of wild-type (WT), A(2A) knockout (KO), and A(2B)KO mice, perfused at constant pressure and constant heart rate, underwent 30 min of global ischemia and 60 min of reperfusion. The adenosine A(1) receptor agonist N(6)-cyclohexyladenosine (CHA; 200 nM) was administrated 10 min before ischemia and for the first 10 min of reperfusion. Treatment with CHA significantly improved postischemic left ventricular developed pressure (74 ± 4% vs. 44 ± 4% of preischemic left ventricular developed pressure at 60 min of reperfusion) and reduced infarct size (30 ± 2% with CHA vs. 52 ± 5% in control) in WT hearts, effects that were blocked by the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (100 nM). Treatments with the A(2A) receptor agonist CGS-21680 (200 nM) and the A(2B) agonist BAY 60-6583 (200 nM) did not exert any beneficial effects. Deletion of adenosine A(2A) or A(2B) receptor subtypes did not alter ischemia-reperfusion injury, but CHA failed to exert a cardioprotective effect in hearts of mice from either KO group. These findings indicate that both adenosine A(2A) and A(2B) receptors are required for adenosine A(1) receptor-mediated cardioprotection, implicating a role for interactions among receptor subtypes.     

Effect of gibberellins A3, A4+7 and A13 and of (−)-kaurene on flowering and extension growth of Impatiens balsamina under different photoperiods

Summary Gibberellins A₃, A₄₊₇ and A₁₃ and (–)-kaurene delay floral-bud initiation and flowering and decrease the number of floral-buds and flowers in Impatiens balsamina under 4-hr photoperiods. They do not have any marked effect under 8-hr photoperiods. Under 16- and 24-hr photoperiods they hasten floral-bud initiation and flowering and increase the number of flowers, the effect being greater under 16- than under 24-hr days and the order of effectiveness being GA₄₊₇>GA₃>GA₁₃>(–)-kaurene.While GA₃ and GA₄₊₇ promote extension growth, the effect being greater with the former, GA₁₃ and (–)-kaurene do not promote it under any photoperiod. The magnitude of stem elongation in different treatments prior to floral-bud initiation increases from 4- to 8-hr photoperiods but decreases under 16- and 24-hr periods, the effect being more under 24-hr although both 16-and 24-hr photoperiods are noninductive for flowering.     

WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity

Neurodegenration is a pathological hallmark of Alzheimer's disease (AD), but the underlying molecular mechanism remains elusive. Here, we present evidence that reveals a crucial role of Wnt5a signaling in this process. We showed that Wnt5a and its receptor Frizzled-5 (Fz5) were up-regulated in the AD mouse brain, and that beta-amyloid peptide (Aβ), a major constituent of amyloid plaques, stimulated Wnt5a and Fz5 expression in primary cortical cultures; these observations indicate that Wnt5a signaling could be aberrantly activated during AD pathogenesis. In support of such a possibility, we observed that inhibition of Wnt5a signaling attenuated while activation of Wnt5a signaling enhanced Aβ-evoked neurotoxicity, suggesting a role of Wnt5a signaling in AD-related neurodegeneration. Furthermore, we also demonstrated that Aβ-induced neurotoxicity depends on inflammatory processes, and that activation of Wnt5a signaling elicited the expression of proinflammatory cytokines IL-1β and TNF-α whereas inhibition of Wnt5a signaling attenuated the Aβ-induced expression of the cytokines in cortical cultures. Our findings collectively suggest that aberrantly up-regulated Wnt5a signaling is a crucial pathological step that contributes to AD-related neurodegeneration by regulating neuroinflammation.