Nonactin,monactin, dinactin,trinactin, and tetranactin. A Raman spectroscopic study

Raman spectra are reported for crystalline nonactin, monactin, dinactin, trinactin, and tetranactin and their solutions in CCl₄, CHCl₃, CH₃OH, and 4:1 (v/v) CH₃OH:CHCl₃. The macrotetrolide nactins selectively bind a wide variety of cations, and are important model compounds for the study of ion complexation. The conformations of nonactin, monactin, and dinactin in solution are similar. Their conformations are found to be sufficiently open to permit the ester carbonyl groups to form hydrogen bonds with CH₃OH; this gives rise to characteristic changes in the vibration frequencies associated with the ester groups. Nonactin, which is the least soluble of the nactins in CH₃OH, is also the least effective at forming hydrogen bonds with CH₃OH. The greater ability of the higher nactins to form hydrogen bonds with CH₃OH may be due to the increased inductive effect of ethyl over methyl side chains, which may increase the dipole moment of the ester carbonyl groups. Spectra of crystalline nonactin, monactin, and tetranactin are fairly similar, while the spectra of dinactin and trinactin comprise a second, distinct family. This is consistent with X-ray crystallographic studies, which show that nonactin and tetranactin form monoclinic crystals, while trinactin is triclinic.     

Molecular hyperdiversity and evolution in very large populations

The genomic density of sequence polymorphisms critically affects the sensitivity of inferences about ongoing sequence evolution, function and demographic history. Most animal and plant genomes have relatively low densities of polymorphisms, but some species are hyperdiverse with neutral nucleotide heterozygosity exceeding 5%. Eukaryotes with extremely large populations, mimicking bacterial and viral populations, present novel opportunities for studying molecular evolution in sexually reproducing taxa with complex development. In particular, hyperdiverse species can help answer controversial questions about the evolution of genome complexity, the limits of natural selection, modes of adaptation and subtleties of the mutation process. However, such systems have some inherent complications and here we identify topics in need of theoretical developments. Close relatives of the model organisms Caenorhabditis elegans and Drosophila melanogaster provide known examples of hyperdiverse eukaryotes, encouraging functional dissection of resulting molecular evolutionary patterns. We recommend how best to exploit hyperdiverse populations for analysis, for example, in quantifying the impact of noncrossover recombination in genomes and for determining the identity and micro‐evolutionary selective pressures on noncoding regulatory elements.     

Optical Monitoring and Detection of Spinal Cord Ischemia

Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings.     

The polymorphic prelude to Bateson-Dobzhansky-Muller incompatibilities

Speciation research has largely assumed that the genetic causes of reproductive isolation are the work of fixed, divergent alleles that interact to cause genetic problems in hybrids: Bateson-Dobzhansky-Muller incompatibilities. However, many recent studies demonstrate substantial heritable polymorphism within species for hybrid incompatibility, herein called variable reproductive isolation (VRI). In this review, I outline the causes and importance of this general phenomenon. I also identify the new challenges of quantifying the relative contributions to reproductive isolation of fixed alleles versus polymorphisms, and the change in these contributions over the course of speciation. Explicit integration of VRI into speciation theory will help to quantify the relative roles of genetic drift and selection in speciation, but this synthesis requires substantial new contributions from both theory and empirical studies.     

Diet and asthma: looking back,moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant''s immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.     

SELDI-TOF MS of quadruplicate urine and serum samples to evaluate changes related to storage conditions

Proteomic profiling with SELDI-TOF MS has facilitated the discovery of disease-specific protein profiles. However, multicenter studies are often hindered by the logistics required for prompt deep-freezing of samples in liquid nitrogen or dry ice within the clinic setting prior to shipping. We report high concordance between MS profiles within sets of quadruplicate split urine and serum samples deep-frozen at 0, 2, 6, and 24 h after sample collection. Gage R&R results confirm that deep-freezing times are not a statistically significant source of SELDI-TOF MS variability for either blood or urine.     

Genetic influences on reproduction of female red deer (Cervus elaphus) (2) seasonal and genetic effects on the superovulatory response to exogenous FSH

This study evaluated the influences of seasons and genotype on the superovulatory response to a standardised oFSH regimen in red deer (Cervus elaphus scoticus) and its hybrids with either wapiti (C.e. nelsoni) or Père David's (PD) deer (Elaphurus davidianus). Adult red deer (n=9), F(1) hybrid wapiti x red deer (n=6), and maternal backcross hybrid PD x red deer (i.e., 14 PD hybrid; n=9) were kept together in the presence of a vasectomised stag for 13 months. At 6 weekly intervals, all hinds received a standardised treatment regimen used routinely to induce a superovulatory response in red deer hinds, with 10 consecutive treatments spanning an entire year. This involved synchronisation with intravaginal progesterone devices and delivery of multiple injections of oFSH (equivalent to 72 units NIH-FSH-S(1)). Laparoscopy to assess ovarian response was performed 6-7 days after the removal of the devices. Both season and genotype had significant effects on ovulation rate (OR) and total follicular stimulation (TFS) (P<0.05). For all the three genotypes, ovarian responses were highest from March to November (breeding season) and lowest in the period from December to January, inclusive. Mean OR for red deer hinds ranged from 3.7 to 1.8 during the breeding season, with no observable trend. All red deer hinds were anovulatory during December and January. A similar pattern occurred for 14 PD hybrids, although mean OR during the breeding seasons were twofold lower than for the red deer. For F(1) wapiti hybrids, the first two treatments in March and April resulted in the highest mean OR observed (15.6 and 11.7, respectively). Thereafter, mean values ranged between 6.3 and 4.7 for the remainder of the breeding season. Furthermore, mean OR of 3.0 and 0.5 were recorded in December and January, respectively. For the red deer and F(1) wapiti hybrids, between-hind variation in OR was not randomly distributed across the treatment dates, indicating that the individuals varied significantly in their ability to respond to oFSH, at least within a given season.In conclusion, the study has shown that relative to red deer, F(1) wapiti hybrid hinds exhibit a higher sensitivity to oFSH, whereas 14 PD hybrid hinds have a lower sensitivity. However, individual variation within genotype was very marked. A seasonal effect was apparent for all genotypes, although some F(1) wapiti hybrid hinds exhibited ovulatory responses throughout the year.     

Correlation of magnetic AC field on cardiac myocyte Ca2+ transients at different magnetic DC levels

The purpose of this study was to determine the effect of extremely low frequency and weak magnetic fields (WMF) on cardiac myocyte Ca²⁺ transients, and to explore the involvement of potassium channels under the WMF effect. In addition, we aimed to find a physical explanation for the effect of WMF on cardiac myocyte Ca²⁺ transients. Indo‐1 loaded cells, which were exposed to a WMF at 16 Hz and 40 nT, demonstrated a 75 ± 4% reduction in cytosolic Ca²⁺ transients versus control. Treatment with the K_ATP channel blocker, glibenclamide, followed by WMF at 16 Hz exposure, blocked the reduction in cytosolic calcium transients while treatment with pinacidil, a K_ATP channel opener, or chromanol 293B, a selective potassium channel blocker of the delayed rectifier K⁺ channels, did not inhibit the effect. Based on these finding and the ion cyclotron resonance frequency theory, we further investigated the effect of WMF by changing the direct current (DC) magnetic field (B₀). When operating different DC magnetic fields we showed that the WMF value changed correspondingly: for B₀ = 44.5 µT, the effect was observed at 17.05 Hz; for B₀ = 46.5 µT, the effect was observed at 18.15 Hz; and for B₀ = 49 µT the effect was observed at 19.1 Hz. We can conclude that the effect of WMF on Ca²⁺ transients depends on the DC magnetic field level. Bioelectromagnetics 33:634–640, 2012. © 2012 Wiley Periodicals, Inc.