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.     

Association between TNF-α promoter G-308A and G-238A polymorphisms and obesity

Tumor necrosis factor-α (TNF-α), an adipokine, is produced in adipocytes, and the elevation of its levels has been linked to obesity and insulin resistance in some population. In this study the relationship between TNF-α promoter gene polymorphism and obesity in an Iranian population has been studied. Subjects were randomly selected from Tehran Cohort Lipid and Glucose Study. Adult participants placed in three groups according to their body mass index (BMI): BMI < 25, 25 ≤ BMI < 30, BMI ≥ 30 and under-18 subjects placed in two groups, under 85th percentile BMI and above 85th percentile. Finally, 244 persons were selected for G-308A and G-238A polymorphisms analysis. The FBS, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, cholesterol levels and blood pressure and HOMA of all subjects were measured. The polymorphism −308 and −238 were revealed by restriction fragment length polymorphism (RFLP; NCOI and MSPI) after the promoter site was amplified by PCR. The allele frequency of TNF-α polymorphism was in the Hardy–Weinberg equilibrium. There was no relation between BMI and the frequency of this allele. The fact that there is no association between G-308A and G-238A TNF-α promoter polymorphisms and obesity probably shows that it is not an important risk factor for obesity and consequently for cardiovascular disease.     

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.     

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.     

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.     

Oligomerization and toxicity of Aβ fusion proteins

This study has found that the Maltose binding protein Aβ42 fusion protein (MBP-Aβ42) forms soluble oligomers while the shorter MBP-Aβ16 fusion and control MBP did not. MBP-Aβ42, but neither MBP-Aβ16 nor control MBP, was toxic in a dose-dependent manner in both yeast and primary cortical neuronal cells. This study demonstrates the potential utility of MBP-Aβ42 as a reagent for drug screening assays in yeast and neuronal cell cultures and as a candidate for further Aβ42 characterization.     

Pollen as food and medicine—A review

Pollen, the male gametophyte of flowering plants, is a high energy material, which is collected by insects and stored as food reserve. Pollen has been used traditionally by humans for religious purposes and as supplementary food. Pollen is a concentrated, energy and vitamin rich food that in contemporary times is not only consumed as a dietary component, but also is used in alternative medical treatments. Pollen has potential imporiance as a supplementary and survival food, and for conditioning of athletes. Pollen has been used medically in prostatitis, bleeding stomach ulcers and some infectious diseases, although such use has been questioned by the medical profession. Pollen may also be used for treatment and prevention of the high-altitude-sickness syndrome. Because some individuals are allergic to pollen, and various pollen species contain specific allergens, individual sensitivities must be tested before pollen is used as a treatment or as a supplementary food.     

HYPERVENTILATION SYNDROME—A Clinical and Physiological Evaluation

There is a chronic hyperventilation syndrome which is much more common, of greater medical significance and far more difficult to diagnose than the better-known acute hyperventilation attack. This chronic syndrome tends to mimic grave organic disease with which it frequently is associated or superimposed.Studies on 250 patients with chronic hyperventilation patterns revealed the rapidity with which biochemical and physiological changes can occur and the characteristics of the resultant symptoms and signs, with particular reference to the heart and lungs.Once the diagnosis is suspected and appropriately confirmed, it is possible to “cure” over 70 per cent of such patients by means of simple therapeutic measures.     

1H, 15N and 13C backbone chemical shift assignment of titin domains A59–A60 and A60 alone

The giant protein titin is the third most abundant protein of vertebrate striated muscle. The titin molecule is >1 μm long and spans half the sarcomere, from the Z-disk to the M-line, and has important roles in sarcomere assembly, elasticity and intracellular signaling. In the A-band of the sarcomere titin is attached to the thick filaments and mainly consists immunoglobulin-like and fibronectin type III-like domains. These are mostly arranged in long-range patterns or ‘super-repeats’. The large super-repeats each contain 11 domains and are repeated 11 times, thus forming nearly half the titin molecule. Through interactions with myosin and C-protein, they are involved in thick filament assembly. The importance of titin in muscle assembly is highlighted by the effect of mutations in the A-band portion, which are the commonest cause of dilated cardiomyopathy, affecting ~1 in 250 (Herman et al. in N Engl J Med 366:619–628, 2012). Here we report backbone ¹⁵N, ¹³C and ¹H chemical shift and ¹³Cβ assignments for the A59–A60 domain tandem from the titin A59–A69 large super-repeat, completed using triple resonance NMR. Since, some regions of the backbone remained unassigned in A60 domain of the complete A59–A60 tandem, a construct containing a single A60 domain, A60sd, was also studied using the same methods. Considerably improved assignment coverage was achieved using A60sd due to its lower mass and improved molecular tumbling rate; these assignments also allowed the analysis of inter-domain interactions using chemical shift mapping against A59–A60.     

Isolation,structure determination and biological activity of A-16686 factors A′ 1, A′ 2 and A′ 3 glycolipodepsipeptide antibiotics

Summary WhenActinoplanes strain ATCC 33076, the producer of A-16686 A1, A2 and A3 complex, is fermented in a suitable medium three additional factors, designated A1, A2 and A3 are produced. These were isolated and characterized, and were shown to differ from the parent components of the original complex by lacking one mannose unit. Bioconversion of A factors into A factors was achieved by incubation with the mycelium ofActinoplanes ATCC 33076. Factor A2 has better antibacterial activity than A2 against some bacteria.