Sex change strategy and the aromatase genes

5′ flanking regions of CYP19A1/A2 genes are reported for three sex changing fish.

Relationship Between Hardness Genes and Quality in Barley (Hordeum vulgare)

Barley (Hordeum vulgare) genotypes were sequenced for polymorphism in the hardness genes, these being the three hordoindoline (hin a, hin b1 and hin b2) genes. The variation in haplotype was determined by sequencing for single nucleotide polymorphisms (SNPs). Polymorphism between each gene was then compared to grain hardness (three methods), malt quality characteristics (hot water extract and friability) and cattle feed quality. Two haplotypes were found in a set of forty barley genotypes. For hin a, two alleles were present, namely hin a1 and hin a2. However, there was no specific hin a allele that was associated with grain hardness, malt and feed quality. Barley has two hin b genes, namely hin b1 and hin b2, and the genotypes tested here had one of two alleles for each gene. However, there were no obvious effects on hardness or quality from either of these hin b alleles. Unlike wheat, where a clear relationship has been demonstrated between a number of SNPs in the wheat hardness genes and quality (soft or hard wheat), there was no such relationship for barley. Despite the wide range in hardness, malt and feed quality, there were only two haplotypes for each of the hin a, hin b1 and hin b2 genes and there was no clear relationship between grain hardness, malt or feed quality. The genotypes used in this study demonstrated that there was a low level of polymorphism in hardness genes in current commercial varieties as well as breeding lines and these polymorphisms had no impact on quality.

Alfven surface waves along cylindrical plasma columns

The properties of Alfven surface waves along a cylindrical plasma column surrounded by vacuum or by another plasma medium are discussed. Both symmetric (m=0) and asymmetric (m=+or-1) modes are found to be dispersive in nature. The interfacial symmetric modes propagate in a certain frequency window ( omega A1, omega As), where omega As is the Alfven surface wave frequency along the interface of two semi-infinite media; when nu A1> nu A2 these modes propagate as backward waves and when nu A1< nu A2 as forward waves. The asymmetric modes change from backward to forward waves at a critical wave number kTr approximately=1.59/a when nu A1< nu A2 or vice versa when nu A1> nu A2.

Effect of Ethanol Extract of Whole Plant of Trichosanthes cucumerina var. cucumerina L. on Gonadotropins, Ovarian Follicular Kinetics and Estrous Cycle for Screening of Antifertility Activity in Albino Rats

Ethanol extract of whole plant of Trichosanthes cucumerina L. var. cucumerina was evaluated for antiovulatory activity in adult rats. The ethanol extract at the doses 200 and 400mg/kg body weight (orally) affected the normal estrous cycle showing a significant increase in estrus and metestrus phases and decrease in diestrus and proestrus phases. The extract also significantly reduced the number of healthy follicles (Class I-Class VI) and corpora lutea and increased the number of regressing follicles (Stage IA, Stage IB, Stage IIA, and Stage IIB). The protein and glycogen content in the ovaries were significantly reduced in treated rats. The cholesterol level was significantly increased, whereas, the enzyme activities like 3b-HSD and 17b-HSD were significantly inhibited in the ovary of treated rats. Serum FSH and LH levels were significantly reduced in the treated groups were measured by RIA. In acute toxicity test, neither mortality nor change in the behavior or any other physiological activities in mice were observed in the treated groups. In chronic toxicity studies, no mortality was recorded and there were no significant differences in the body and organ weights were observed between controls and treated rats. Hematological analysis showed no significant differences in any of the parameters examined (RBC, WBC count and Hemoglobin estimation). These observations showed the antiovulatory activity of ethanol extract of whole plant of Trichosanthes cucumerina L. var. cucumerina in female albino rats.

Effects of increasing neuromuscular electrical stimulation current intensity on cortical sensorimotor network activation: A time domain fNIRS study

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O₂Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O₂Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O₂Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Behaviour of methylmethacrylate-acrylonitrile random copolymers in dilute solution

Studies on the dilute solution properties of methylmethacrylate-acrylonitrile random copolymers of three different compositions, 0.236, 0.5 and 0.74 mole fraction (m.f.) of acrylonitrile (AN) designated as MAa, MAb and MAc, respectively, have been made in good solvents and theta solvents. MAa has been studied in benzene (Bz) and ethylacetate (EAc). MAb in acetonitrile (MeCN), dimethyl sulphoxide (DMSO) and a binary solvent mixture of Bz and dimentyl formamide (DMF) in the volume ratio 6.5:1 designated as BM1 and MAc in MeCN, DMSO and Bz + DMF in the volume ratio 1.667:1 designated as BM2. The Mark-Houwink exponent ‘a’ reveals that Bz is a theta solvent for MAa at 20°C. For MAb and MAc, BM1 and BM2, respectively have ‘a’ values of 0.5 at all three temperatures studied (30°, 40° and 50°C). It is not clear whether they represent theta states or preferential adsorption plays a role complicating the behaviour in solution. The values of A2 are very low in MeCN considering that it is a very good solvent for the copolymer, ‘a’ values for MAb and MAc being 0.75 and 0.7, respectively.

A note on the existence of Alfvén surface waves

The Alfvén surface waves can arise due to the discontinuity in the Alfvén speed across the interface along which these waves propagate. This note studies the relationship between v A1 and v A2 which is required for the existence of Alfvén surface waves in low-beta.

Estimation of red blood cell lifespan from alveolar carbon monoxide measurements

Measurement of alveolar carbon monoxide (CO) presents a facile technique to estimate the lifespan, L, of red blood cells (RBCs) in vivo. Several recent studies employ this technique and calculate L (in days) using the expression, L = 13.8 (Hb)/P-CO(end), where (Hb) is the concentration (in g/dL) of hemoglobin in blood, and P-CO(end) is the endogenous production of CO (in ppm). Implicit in this calculation is the assumption that the fraction, f, of endogenous CO production due to RBC turnover is a constant equal to 0.7, which yields the expected RBC lifespan, L approximate to 120 days, in normal controls. In anemic patients, however, enhanced RBC turnover may increase f substantially above 0.7. The above expression then overestimates L. Here, we deriv an alternative tive expression, L = 3390[Hb]/322P(CO (end)-110, that accounts explicitly for the dependence of f on the rate of RBC turnover and thereby provides more accurate estimates of L without requiring additional measurements. Using the latter expression, we recalculate L from recent measurements on hepatitis C virus infected patients undergoing treatment with ribavirin. We find that our estimates of L in these patients (39 +/- 13 days) are significantly lower than current estimates (46 +/- 14 days), indicating that ribavirin affects RBC survival more severely than expected from current studies. Our expression for L is simple to employ in a clinical setting and would render the broadly applicable technique of alveolar CO measurement for the estimation of RBC lifespan more accurate.

Experimental and computational studies on lipoprotein lipolysis at acidic pH

Atherosclerosis is a disease of the arteries; its characteristic features include chronic inflammation, extra- and intracellular lipid accumulation, extracellular matrix remodeling, and an increase in extracellular matrix volume. The underlying mechanisms in the pathogenesis of advanced atherosclerotic plaques, that involve local acidity of the extracellular fluid, are still incompletely understood. In this thesis project, my co-workers and I studied the different mechanisms by which local extracellular acidity could promote accumulation of the atherogenic apolipoprotein B-100 (apoB-100)-containing plasma lipoprotein particles in the inner layer of the arterial wall, the intima. We found that lipolysis of atherogenic apoB-100-containing plasma lipoprotein particles (LDL, IDL, and sVLDL) by the secretory phospholipase A2 group V (sPLA2-V) enzyme, was increased at acidic pH. Also, the binding of apoB-100-containing plasma lipoprotein particles to human aortic proteoglycans was dramatically enhanced at acidic pH. Additionally, lipolysis by sPLA2-V enzyme further increased this binding. Using proteoglycan-affinity chromatography, we found that sVLDL lipoprotein particles consist of populations, differing in their affinities toward proteoglycans. These populations also contained different amounts of apolipoprotein E (apoE) and apolipoprotein C-III (apoC-III); the amounts of apoC-III and apoE per particle were highest in the population with the lowest affinity toward proteoglycans. Since PLA2-modification of LDL particles has been shown to change their aggregation behavior, we also studied the effect of acidic pH on the monolayer structure covering lipoprotein particles after PLA2-induced hydrolysis. Using molecular dynamics simulations, we found that, in acidity, the monolayer is more tightly packed laterally; moreover, its spontaneous curvature is negative, suggesting that acidity may promote lipoprotein particles fusion. In addition to extracellular lipid accumulation, the apoB-100-containing plasma lipoprotein particles can be taken up by inflammatory cells, namely macrophages. Using radiolabeled lipoprotein particles and cell cultures, we showed that sPLA2-V-modification of LDL, IDL, and sVLDL lipoproteins particles, at neutral or acidic pH, increased their uptake by human monocyte-derived macrophages.

Sequence variants in three loci influence monocyte counts and erythrocyte volume

Blood cells participate in vital physiological processes, and their numbers are tightly regulated so that homeostasis is maintained. Disruption of key regulatory mechanisms underlies many blood-related Mendelian diseases but also contributes to more common disorders, including atherosclerosis. We searched for quantitative trait loci (QTL) for hematology traits through a whole-genome association study, because these could provide new insights into both hemopoeitic and disease mechanisms. We tested 1.8 million variants for association with 13 hematology traits measured in 6015 individuals from the Australian and Dutch populations. These traits included hemoglobin composition, platelet counts, and red blood cell and white blood cell indices. We identified three regions of strong association that, to our knowledge, have not been previously reported in the literature. The first was located in an intergenic region of chromosome 9q31 near LPAR1, explaining 1.5% of the variation in monocyte counts (best SNP rs7023923, p=8.9x10(-14)). The second locus was located on chromosome 6p21 and associated with mean cell erythrocyte volume (rs12661667, p=1.2x10(-9), 0.7% variance explained) in a region that spanned five genes, including CCND3, a member of the D-cyclin gene family that is involved in hematopoietic stem cell expansion. The third region was also associated with erythrocyte volume and was located in an intergenic region on chromosome 6q24 (rs592423, p=5.3x10(-9), 0.6% variance explained). All three loci replicated in an independent panel of 1543 individuals (p values=0.001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate.

Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has a relatively high heritability, and on the other hand adenosine regulates sleep homeostasis and might also be involved in mood modulation, adenosine-related genes should be considered for their possible contribution to a predisposition for depression and disturbed sleep in humans. Depression is a complex disorder likely involving the abnormal functioning of several genes. Novel target genes which could serve as the possible common substrates for depression and comorbid disturbed sleep should be identified. In this way specific brain areas related to sleep regulation should be studied by using animal model of depression which represents more homogenous phenotype as compared to humans. It is also important to study these brain areas during the development of depressive-like features to understand how early changes could facilitate pathophysiological changes in depression. Aims and methods: We aimed to find out whether, in the basal forebrain, adenosine induces recovery non-rapid eye movement (NREM) sleep after prolonged waking through the A1 or/and A2A receptor subtype. A1 and A2A receptor antagonists were perfused into the rat basal forebrain during 3 h of sleep deprivation, and the amount of NREM sleep and delta power during recovery NREM sleep were analyzed. We then explored whether polymorphisms in genes related to the metabolism, transport and signaling of adenosine could predispose to depression accompanied by signs of disturbed sleep. DNA from 1423 individuals representative of the Finnish population and including controls and cases with depression, depression accompanied by early morning awakenings and depression accompanied by fatigue, was used in the study to investigate the possible association between polymorphisms from adenosine-related genes and cases. Finally to find common molecular substrates of depression and disturbed sleep, gene expression changes were investigated in specific brain areas in the rat clomipramine model of depression. We focused on the basal forebrain of 3-week old clomipramine-treated rats which develop depressive-like symptoms later in adulthood and on the hypothalamus of adult female clomipramine-treated rats. Results: Blocking of the A1 receptor during sleep deprivation resulted in a reduction of the recovery NREM sleep amount and delta power, whereas A2A receptor antagonism had no effect. Polymorphisms in adenosine-related genes SLC29A3 (equilibrative nucleoside transporter type 3) in women and SLC28A1 (concentrative nucleoside transporter type 1) in men associated with depression alone as well as when accompanied by early morning awakenings and fatigue. In Study III the basal forebrain of postnatal rats treated with clomipramine displayed disturbances in gamma-aminobutyric acid (GABA) receptor type A signaling, in synaptic transmission and possible epigenetic changes. CREB1 was identified as a common transcription denominator which also mediates epigenetic regulation. In the hypothalamus the major changes included the expression of genes in GABA-A receptor pathway, K+ channel-related, glutamatergic and mitochondrial genes, as well as an overexpression of genes related to RNA and mRNA processing. Conclusions: Adenosine plays an important role in sleep homeostasis by promoting recovery NREM sleep via the A1 receptor subtype in the basal forebrain. Also adenosine levels might contribute to the risk of depression with disturbed sleep, since the genes encoding nucleoside transporters showed the strongest associations with depression alone and when accompanied by signs of disturbed sleep in both women and men. Sleep and mood abnormalities in major depressive disorder could be a consequence of multiple changes at the transcriptional level, GABA-A receptor signaling and synaptic transmission in sleep-related basal forebrain and the hypothalamus.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

The discovery of genetic factors that contribute to schizophrenia susceptibility is a key challenge in understanding the etiology of this disease. Here, we report the identification of a novel schizophrenia candidate gene on chromosome 1q32, plexin A2 (PLXNA2), in a genome-wide association study using 320 patients with schizophrenia of European descent and 325 matched controls. Over 25,000 single-nucleotide polymorphisms (SNPs) located within approximately 14,000 genes were tested. Out of 62 markers found to be associated with disease status, the most consistent finding was observed for a candidate locus on chromosome 1q32. The marker SNP rs752016 showed suggestive association with schizophrenia (odds ratio (OR) = 1.49, P = 0.006). This result was confirmed in an independent case-control sample of European Americans (combined OR = 1.38, P = 0.035) and similar genetic effects were observed in smaller subsets of Latin Americans (OR = 1.26) and Asian Americans (OR = 1.37). Supporting evidence was also obtained from two family-based collections, one of which reached statistical significance (OR = 2.2, P = 0.02). High-density SNP mapping showed that the region of association spans approximately 60 kb of the PLXNA2 gene. Eight out of 14 SNPs genotyped showed statistically significant differences between cases and controls. These results are in accordance with previous genetic findings that identified chromosome 1q32 as a candidate region for schizophrenia. PLXNA2 is a member of the transmembrane semaphorin receptor family that is involved in axonal guidance during development and may modulate neuronal plasticity and regeneration. The PLXNA2 ligand semaphorin 3A has been shown to be upregulated in the cerebellum of individuals with schizophrenia. These observations, together with the genetic results, make PLXNA2 a likely candidate for the 1q32 schizophrenia susceptibility locus.

A note on the existence of Alfven surface waves

The Alfven surface waves can arise due to the discontinuity in the Alfven speed across the interface along which these waves propagate. This note studies the relationship between v A1 and v A2 which is required for the existence of Alfven surface waves in low-beta plasma.

Strategies of synthesis based on dihydrobenzenes

1-Methoxycyclohexa-1,4-dienes are readily available from the metal-ammonia-alcohol reduction of aromatic ethers. The use of these dihydrocompounds in the synthesis of a variety of natural products is reviewed.