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Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.
The possibility that life, primitive or advanced, might exist in other places of the Universe has occupied the minds of scientists and lay-people for thousands of years. It is only in the last 25 years, however, that we have finally begun to search for answers to this profound question using experimental techniques. The goal of Astronomy is to understand the origin and evolution of planets, stars, galaxies and of the Universe as a whole. The appearance of life is an integral part of this whole process and our picture of the Universe will never be complete until we will comprehend also the significance of life in the process of Cosmic Evolution.
The Ca II K line serves as an important tool in determining the physics of the photosphere-chromosphere region of the solar atmosphere (Cram 1983). To date detailed analyses have centred on the study of line intensity profiles.
Increasing recognition of the extent to which nitrous oxide (N2O) contributes to climate change has resulted in greater demand to improve quantification of N2O emissions, identify emission sources and suggest mitigation options. Agriculture is by far the largest source and grasslands, occupying c. 0·22 of European agricultural land, are a major land-use within this sector. The application of mineral fertilizers to optimize pasture yields is a major source of N2O and with increasing pressure to increase agricultural productivity, options to quantify and reduce emissions whilst maintaining sufficient grassland for a given intensity of production are required. Identification of the source and extent of emissions will help to improve reporting in national inventories, with the most common approach using the IPCC emission factor (EF) default, where 0·01 of added nitrogen fertilizer is assumed to be emitted directly as N2O. The current experiment aimed to establish the suitability of applying this EF to fertilized Scottish grasslands and to identify variation in the EF depending on the application rate of ammonium nitrate (AN). Mitigation options to reduce N2O emissions were also investigated, including the use of urea fertilizer in place of AN, addition of a nitrification inhibitor dicyandiamide (DCD) and application of AN in smaller, more frequent doses. Nitrous oxide emissions were measured from a cut grassland in south-west Scotland from March 2011 to March 2012. Grass yield was also measured to establish the impact of mitigation options on grass production, along with soil and environmental variables to improve understanding of the controls on N2O emissions. A monotonic increase in annual cumulative N2O emissions was observed with increasing AN application rate. Emission factors ranging from 1·06–1·34% were measured for AN application rates between 80 and 320 kg N/ha, with a mean of 1·19%. A lack of any significant difference between these EFs indicates that use of a uniform EF is suitable over these application rates. The mean EF of 1·19% exceeds the IPCC default 1%, suggesting that use of the default value may underestimate emissions of AN-fertilizer-induced N2O loss from Scottish grasslands. The increase in emissions beyond an application rate of 320 kg N/ha produced an EF of 1·74%, significantly different to that from lower application rates and much greater than the 1% default. An EF of 0·89% for urea fertilizer and 0·59% for urea with DCD suggests that N2O quantification using the IPCC default EF will overestimate emissions for grasslands where these fertilizers are applied. Large rainfall shortly after fertilizer application appears to be the main trigger for N2O emissions, thus applicability of the 1% EF could vary and depend on the weather conditions at the time of fertilizer application.
Using semi-empirical isochrones, we find the age of the Taurus star-forming region to be 3-4 Myr. Comparing the disc fraction in Taurus to young massive clusters suggests discs survive longer in this low density environment. We also present a method of photometrically de-reddening young stars using iZJH data.
A number of copy number variants (CNVs) have been suggested as
susceptibility factors for schizophrenia. For some of these the data
remain equivocal, and the frequency in individuals with schizophrenia is
To determine the contribution of CNVs at 15 schizophrenia-associated loci
(a) using a large new data-set of patients with schizophrenia
(n = 6882) and controls (n = 6316),
and (b) combining our results with those from previous studies.
We used Illumina microarrays to analyse our data. Analyses were
restricted to 520 766 probes common to all arrays used in the different
We found higher rates in participants with schizophrenia than in controls
for 13 of the 15 previously implicated CNVs. Six were nominally
significantly associated (P<0.05) in this new
data-set: deletions at 1q21.1, NRXN1, 15q11.2 and
22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi
Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were
of maternal origin. When combined with published data, 11 of the 15 loci
showed highly significant evidence for association with schizophrenia
We strengthen the support for the majority of the previously implicated
CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9%
of controls carry a large, detectable CNV at one of these loci. Routine
CNV screening may be clinically appropriate given the high rate of known
deleterious mutations in the disorder and the comorbidity associated with
these heritable mutations.
Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.
We compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).
Frequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions.
Current subthreshold depressive symptoms in early HD are associated with microstructural changes – without concomitant brain volume loss – in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology.
This editorial proposes a shift in emphasis in the field of mental health epidemiology in conflict-affected settings. After a brief summary of the nature of contemporary armed conflicts, we consider the current and potential roles that epidemiology can play with regard to: (1) establishing the burden of mental disorders; (2) identifying risk and protective factors; and (3) intervention research. We advocate for improved methodological rigor; more attention to mixed methods approaches and multi-level longitudinal research; inclusion of the determinants of mental health beyond conflict-related violence; and consideration of a wider array of mental health outcomes. We particularly highlight the importance of expanding interest to epidemiological research that advances prevention and promotion interventions (e.g., in the early childhood period), in order to fill the gap between epidemiology and mental health practice in conflict-affected settings.
A 2,3-dibutoxy-1,4-phenylenevinylene comonomer was incorporated into a distyrylbenzene derivative 11. Novel 1,2-disubstituted-3,6-dibromobenzene comonomers 15 and 18 were prepared by directed metallation. Copolymerization of 11with a 9,9-dioctylfluorene-2,7-diboronate ester 1 yielded a green fluorescent polymer while copolymerization of 15 and 18 with the 9,9-dihexylfluorene-2,7-diboronate 22 afforded promising blue fluorescent polymers 23 and 24 respectively.
Growth of ZnSe on GaAs from H2S9 and Zn[N(TMS)2]2 precursors has been demonstrated. When Et2Zn is used as the zinc precursor a higher quality deposit is obtained. Results of experiments employing Et2Zn as the main zinc source with Zn[N(TMS)2]2 introduced at a dopant level indicate nitrogen has been incorporated. Final thin films were characterized by PL, XRD, SIMS, and Raman.
BPDA-PDA poly(amic acid) precursor was functionalized through its carboxylic acid groups being linked with a crosslinkable aminoalkyl methacrylate, 2-(dimethylamino)ethyl methacrylate (DMAEM), by acid/base complexation. BPDA-PDA polyimide films, which were thermally imidized from the precursors complexed with various amounts of DMAEM, were characterized by means of wide angle x-ray diffraction, stress-strain analysis, and residual stress analysis. The structure and properties of the BPDA-PDA polyimide film were dependent upon the history of the precursor, that is, the complexation of the poly(amic acid) precursor with DMAEM. The molecular packing order was enhanced with the history of DMAEM loading while the molecular order along the chain axis was disrupted. Overall, physical properties, such as mechanical properties and residual stress, were degraded with DMAEM loading. The moisture induced stress relaxation behavior was sensitive to the history of DMAEM loading, whereas the creep induced stress relaxation was varied little due to its high Tg. These properties are understood in terms of structure/property relationships, as well as microvoids, which were possibly generated by outgassing the bulky DMAEM pendent groups during thermal imidization.
Ferroelectric and other high dielectric constant metal oxides currently are sought-after for a variety of applications in the electronics industry. To meet the demand of preparation of these interesting materials in a manner compatible with traditional silicon-based fabrication procedures, chemical vapor deposition routes are desired for film growth. Compounds displaying high vapor phase stability are necessary as precursors for these applications. Additionally, in general, it is preferred to utilize compounds in a liquid state, due to the more rapid re-establishment of equilibrium at a liquid-vapor interface, compared to that present at a solid-vapor interface. This combination of desired molecular properties, in turn, presents a great challenge to the coordination chemist. Several of the metals of interest for these uses reside in groups 2–5. Common design features are emerging for the ligands best suited for attachment to these metals for subsequent utilization in the deposition of metal oxides. In order to achieve coordinative saturation of the relatively high ionic radii exhibited by most of these elements, multidentate, monoanionic ligands are relied upon. In the past, most often, homoleptic ligand sets have been employed, thereby reducing the chance for ligand scrambling to occur during the growth process. Such disproportionation processes have been credited, in previous work, with the observation of a temporal decay in vapor pressure of heteroleptic compounds. In some interesting new developments, it has been found that heteroleptic compounds possess sufficient vapor phase integrity to permit their evaluation as CVD precursors. These, and related, results are presented herein.
Chemical methods of processing ceramics have the potential to overcome many of the processing-related obstacles that have hindered widespread commercialization. The Southwest Research Institute (SwRI) has focused on the development of polymeric precursors to silicon nitride (Si3N4). One such precursor, perhydropolysilazane (or PHPS), has been shown to be a useful binder for Si3N4 powder processing, a useful matrix precursor for the polymer infiltration/pyrolysis (PIP) processing of fiber-reinforced Si3N4, and a useful ceramic coating precursor for the repair of oxidation protection coatings on carbon-carbon composites. While conventional, thermal pyrolyses of these preceramnics has been sufficient to demonstrate their potential, substantial cost savings could be realized if the polymer-to-ceramic conversion could be instigated with electromagnetic energy. We have investigated the use of millimeter wave heating as a means of converting PHPS into Si3N4, and report here the results of our efforts to produce bulk compacts, coatings, and fiber-reinforced ceramics.
Previously we have examined the effects of diets deficient in folic acid ( − F) or folate deficient with low methionine and choline ( − F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the − F diet. When dams were fed the − F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the − F LM LC group but not in the − F group. Metabolic enzymes associated with lipid metabolism changed in both the − F and − F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the − F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the − F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARα and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues.
A reliable grading system allows the clinician to classify disease severity, monitor progress and evaluate treatment efficacy. There is no currently accepted grading system for vocal process granuloma of the larynx.
To evaluate the reliability of a new grading system for vocal process granuloma.
All vocal process granuloma images from a digital laryngeal image library were abstracted. Granulomas were graded on a one to four system, as follows: grade one, sessile, non-ulcerative granuloma limited to vocal process; grade two, pedunculated or ulcerated granuloma limited to vocal process; grade three, granuloma extending past vocal process but not crossing midline of airway in fully abducted position; and grade four, granuloma extending past vocal process and past the midline of the airway in the fully abducted position. The granulomas were additionally graded A if unilateral and B if bilateral. Two laryngologists and two otolaryngology residents rated the granulomas on two separate occasions. Intra- and inter-observer reliability was evaluated with the kappa (κ) test statistic.
Thirty-five vocal process granulomas were identified. The percentage intra-observer agreement for the two laryngologists was 97 and 100 per cent (κ = 0.94 and 1.00, respectively). The percentage inter-observer agreement between the two laryngologists was 91 per cent (κ = 0.83). The percentage intra-observer agreement for the two residents was 89 and 91 per cent (κ = 0.83 and 0.77, respectively). The percentage inter-observer agreement between the two residents was 83 per cent (κ = 0.67).
The proposed grading system for vocal process granuloma displayed excellent intra- and inter-observer reliability among residents and experienced laryngologists.
The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (–F) or in three key methyl donors, folic acid, choline and methionine (–FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism, energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both –F and –FLMLC diets. The mRNA for PPARα and PPARγ and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the –FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the –F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the –FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.
Maternal malnutrition can lead to fetal abnormalities and increase susceptibility to disease in later life. Rat models have been developed to study the physiology and metabolism underlying this phenomenon. One particular model of 50% protein restriction during pregnancy, the low-protein diet (LPD) supplemented with methionine, has been developed to investigate the underlying mechanisms. Recent studies have shown that rats fed a LPD during only the first 4 d of pregnancy produce offspring that develop hypertension. These results suggest that the very earliest stages of embryo development are susceptible to diet-induced heritable changes. We demonstrate a marked elevation of maternal serum homocysteine (hcy) concentrations during the initial phases of pregnancy in both rats and mice fed an LPD. Fetal growth and many of the circulating amino acids are similarly perturbed in both rats and mice fed the LPD during pregnancy, indicating that the response to the LPD diet is similar in rats and mice. These findings allow us to exploit the advantages of the mouse experimental system in future analyses aimed at understanding the molecular basis of fetal programming. Our present findings are discussed with particular reference to mechanisms which may initiate fetal programming, and to the feasibility of dietary interventions aimed at reducing early pregnancy loss and pre-eclampsia in man.