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Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26–28 weeks’ gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother–infant pairs from the Growing Up in Singapore Towards Healthy Outcomes cohort. Linear regressions adjusted for key confounders examined associations of maternal vitamin B12 with cognitive, receptive and expressive language, fine and gross motor subscales. Co-occurrence of maternal vitamin B12 with folate or vitamin B6 insufficiencies on child’s cognition was explored. Average maternal plasma vitamin B12 concentrations was 220·5 ± 80·5 pmol/l; 15 % and 41 % of mothers were vitamin B12 deficient (<148 pmol/l) and insufficient (148–220·9 pmol/l), respectively. Infants of mothers with vitamin B12 deficiency had 0·42 (95 % CI −0·70, −0·14) sd lower cognitive scores, compared with infants of mothers with sufficient vitamin B12. Co-occurrence of maternal vitamins B12 and B6 insufficiencies was associated with 0·37 (95 % CI −0·69, −0·06) sd lower cognitive scores in infants compared with infants of mothers sufficient in both vitamins. No significant associations were observed with other subscales. Study findings suggest the possible need to ensure adequate vitamin B12 during pregnancy. The impact of co-occurrence of maternal B-vitamins insufficiencies on early cognitive development warrants further investigation.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
The functional composition of plant communities in montane regions has been studied for decades, and most recent analyses find that environmentally favourable landscapes at lower altitudes tend to be dominated by species with resource-acquisitive traits, while more resource-conservative taxa dominate higher-altitude communities. However, it is unclear the extent to which this pattern is driven by co-gradient variation within clades or changes in clade representation across the gradient. To test for co-gradient variation, species composition, phylogenetic structure and functional traits were quantified for 97 species within the plant family Melastomataceae at five locations across a 2500-m altitudinal gradient along Volcán Barva in Costa Rica. Average melastome leaf force to punch, specific leaf area and leaf size vary with altitude, while four other functional traits do not. Taxonomic dissimilarity between communities was correlated with altitudinal difference, while phylogenetic dissimilarity was correlated with altitudinal dissimilarity only when measured with a metric that emphasizes shallow turnover of the tips of the phylogeny. These results highlight how species turnover may be more pronounced than functional or phylogenetic variation along altitudinal gradients. In addition, these results highlight the conservation value of lowland tropical forests, which here harbour a disproportionate amount of phylogenetic and functional diversity.
OBJECTIVES/SPECIFIC AIMS: Our long-term goal is to elucidate the molecular mechanisms and virulence factors that control the differential presentation of infection with Salmonella typhimurium and Salmonella typhi. The objectives of this study are to study the mechanisms that enable S. typhi to trigger a decreased inflammatory response in comparison with S. typhimurium and evade detection by the immune system, leading to the development of asymptomatic chronic carriage of S. typhi. METHODS/STUDY POPULATION: A loss of function eptB mutant S. typhimurium strain was generated. Lipopolysaccharide (LPS) was isolated from wild-type and eptB mutant S. typhimurium and wild-type S. typhi. Binding of LPS to recombinant intelectin was tested by dot blot and enzyme-linked immunosorbant assay (ELISA). C57BL/6 mice were infected with wild-type or eptB mutant S. typhimurium by oral gavage and inflammatory cytokines in the spleen, liver, and Peyer’s patches were measured by qPCR. RESULTS/ANTICIPATED RESULTS: LPS isolated from wild-type S. typhimurium is not bound by intelectin, a protein that has been proposed to function in innate immunity and that is known to be able to bind certain moieties within LPS. Conversely, LPS isolated from eptB mutant S. typhimurium and wild-type S. typhi, which lacks a functional eptB, is bound by intelectin. Mice infected with an eptB mutant S. typhimurium exhibit decreased expression of inflammatory cytokines in the spleen compared to mice infected with the wild type S. typhimurium, suggesting that loss of eptB function allows a nontyphoidal Salmonella serovar to mimic the stealth phenotype of typhoidal serovars. Together, these results suggest that loss of eptB function allows intelectin to bind to and detoxify Salmonella LPS, leading to decreased systemic inflammation during infection. DISCUSSION/SIGNIFICANCE OF IMPACT: These results have broad implications for how pathogens such as S. typhimurium induce systemic shock during infection and may also help to explain a mechanism for how S. typhi is able to evade immune detection and enhance dissemination to systemic sites, leading to development of the asymptomatic chronic carrier state. Further investigation of this novel virulence mechanism will mark a decisive step forward in understanding the mechanisms underlying the differential pathogenesis of S. typhimurium-induced gastroenteritis and S. typhi-induced typhoid fever. Additionally, these results contribute to our understanding of the interactions between host and pathogen in affecting disease presentation, which will have wide appeal among researchers interested in microbial pathogenesis and the contribution of host-pathogen interactions to health and disease.
Two types of diet – standard and atherogenic – were used to study the effect of wheat or wheat–rye breads supplemented with 20 % acid whey concentrate after ultrafiltration on the physiological response of growing rats. The acid whey concentrate after ultrafiltration used in rat diets caused reduced weight gain (for atherogenic diet with wheat bread); growth of caecum tissue and digesta weight; a decrease in the pH of caecum digesta (for atherogenic diet); reduced activity of bacterial glycolytic enzymes; and a significant increase in total SCFA for both types of diet with wheat–rye breads containing acid whey concentrate. For wheat bread with acid whey, in standard diet, a statistically significant increase was found in the population of bifidobacteria. The results showed that the acid whey concentrates could be used as a valuable food ingredient.
Faster eating rates are associated with increased energy intake, but little is known about the relationship between children’s eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children’s BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.
Frostbite is a common yet challenging injury to both diagnose and treat. McCauley’s frostbite treatment protocol consists of 12 treatments that might well represent the standard of care. However, its effectiveness in preventing operative intervention has yet to be examined. Our objectives were to characterize frostbite injuries in Eastern Ontario, identify risk factors for deep injuries, and assess the protocol’s efficacy in preventing operative outcomes.
This cohort study examined patients with frostbite over ten years at a tertiary care hospital. Demographics and predisposing factors were recorded. Frostbite severity was categorized into superficial or deep. Treatments were recorded, including adherence to protocol and operative outcome.
Of the 265 frostbite patients identified, deep frostbite accounted for 56 (21.1%, 95% CI: 16.2–26.1%), of whom 20 (35.7%) had an operative outcome. Amputation occurred in 16 (28.6%) of deep injuries and debridement in 5 (8.9%). Risk factors for deep frostbite were older age (p =0.002), smoking (p <0.001), male sex (p =0.056) and alcohol abuse (p =0.056). None of the patients with deep frostbite had all 12 treatments performed. Adherence to protocol ranged from 0.0% to 48.2% per treatment. The rate of operative intervention was 7.7% in patients with deep frostbite who did not have any McCauley’s frostbite treatments and ranged from 0.0% to 100.0% per treatment in those who did receive treatments.
The frostbite protocol was not regularly followed and therefore its efficacy in preventing operative intervention could not be determined. Further, none of the individual treatments in the protocol were associated with preventing operative intervention. We recommend that future research focus on identifying effective individual treatments.
Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable); and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair samples from 109 (74 female) subjects (age range 12–21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors — perceived stress, symptoms of depression, and neuroticism (r = 0.22–0.33) — but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47–0.60) in those subjects with HCC >11.36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger sample but raise the interesting question of the direction of causation between these variables.
We infer the absolute time dependence of kinematic gas temperature along a proposed orbit of molecular clouds in the Central Molecular Zone (CMZ) of the Galactic Center (GC). Ammonia gas temperature maps are one of the results of the “Survey of Water and Ammonia in the Galactic Center” (SWAG, PI: J. Ott); the dynamical model of molecular clouds in the CMZ was taken from Kruijssen et al. (2015). We find that gas temperatures increase as a function of time in both regimes before and after the cloud passes pericenter on its orbit in the GC potential. This is consistent with the recent proposal that pericenter passage triggers gravitational collapse. Other investigated quantities (line width, column density, opacity) show no strong sign of time dependence but are likely dominated by cloud-to-cloud variations.
X-ray data show that substantial quantities of hot gas are cooling near the centres of many clusters and groups of galaxies. The existence of such cooling flows has been challenged because of the lack of evidence for star formation from the cooled gas. Spectra of cooling flow galaxies show filling in of the continuum shortward of the break at 4000 Å relative to normal elliptical galaxies. This is consistent with some continuing star formation. Extended regions of line emission are commonly associated with cooling flows. If the initial-mass-function of the newly formed stars which affect the 4000 Å break is like that which applies in the solar neighbourhood, then these stars can also power the line emission. The strength of the 4000 Å break is shown to correlate with the Hβ flux in the manner expected when this is the case. This allows us to esimate the star formation rate from the line luminosity.
The rate of star formation required to account for the line emission still falls well short of the rate at which gas is inferred to be cooling. It is argued that, nevertheless, the cooling gas is probably forming into stars. The overall initial-mass-function must be different from that which applies in the solar neighbourhood, but this should not be surprising given the different ambient conditions in a cooling flow.
As part of the activities of the Collaborative Research Centre ‘SFB 350’, measurements of geodetic and geodynamic changes in the area of the Lower Rhine Embayment and the Rhenish Shield are being performed at different scales in space and time. Continuous borehole tilt measurements and repeated microgravimetric surveys yield information on the local stability of the ground and changes in horizontal gravity gradients that are both dominated by seasonal fluctuations. Results of more than seven years of regular GPS campaigns are discussed in terms of vertical and horizontal point motions. The most prominent motions are man-induced effects occurring in or near the browncoal mining areas, where groundwater withdrawal produces subsidence of up to 2.2 cm/y in the area under investigation. Horizontal and vertical motions at other GPS points are smaller by one order of magnitude and in most cases are only marginally detectable. The eastward motion of two points in the Bergisches Land and the westward motion of two points in the Eifel near the Belgian border may be interpreted as a result of the ongoing extension of the Cenozoic rift system in the western part of the Eurasian plate.
Age-related hearing impairment (ARHI) is a common condition with complex etiology but a recognized genetic component. Heritability estimates for pure tone audiogram-determined hearing ability lie in the range 26–75%. The speech-in-noise (SIN) auditory test, however, may be better at encapsulating ARHI symptoms, particularly the diminished ability to segregate environmental sounds into comprehendible auditory streams. As heritability of SIN has not previously been reported, we explored the genetic and environmental contributions to ARHI determined by SIN in 2,076 twins (87.8% female) aged 18–87 (mean age 54.4). SIN was found to be significantly heritable (A, unadjusted for age = 40%; 95% confidence intervals, CI = 32%–47%). With age adjustment, heritability fell (A = 25%; 95% CI = 16–33%), and a relatively strong influence of environmental exposure unshared within twin siblings was identified (E = 75%). To explore the environmental aspects further, we assessed the influence of diet (through the Food Frequency Questionnaire, FFQ), smoking (through self-report and cotinine metabolite levels) and alcohol intake (through the FFQ). A negative influence of high cholesterol diet was observed after adjustment (p = .037). A protective effect of raised serum high-density lipoprotein (HDL) cholesterol levels was observed after adjustment (p = .004). This study is the first assessment of the genetic and environmental influence on SIN perception. The findings suggest SIN is less heritable than pure tone audiogram (PTA) ability and highly influenced by the environment unique to each twin. Furthermore, a possible role of dietary fat in the etiology of ARHI is highlighted.
Shorter telomere length (TL) has found to be associated with lower birth weight and with lower cognitive ability and psychiatric disorders. However, the direction of causation of these associations and the extent to which they are genetically or environmentally mediated are unclear. Within-pair comparisons of monozygotic (MZ) and dizygotic (DZ) twins can throw light on these questions. We investigated correlations of within pair differences in telomere length, IQ, and anxiety/depression in an initial sample from Brisbane (242 MZ pairs, 245 DZ same sex (DZSS) pairs) and in replication samples from Amsterdam (514 MZ pairs, 233 DZSS pairs) and Melbourne (19 pairs selected for extreme high or low birth weight difference). Intra-pair differences of birth weight and telomere length were significantly correlated in MZ twins, but not in DZSS twins. Greater intra-pair differences of telomere length were observed in the 10% of MZ twins with the greatest difference in birth weight compared to the bottom 90% in both samples and also in the Melbourne sample. Intra-pair differences of telomere length and IQ, but not of TL and anxiety/depression, were correlated in MZ twins, and to a smaller extent in DZSS twins. Our findings suggest that the same prenatal effects that reduce birth weight also influence telomere length in MZ twins. The association between telomere length and IQ is partly driven by the same prenatal effects that decrease birth weight.
African great apes are susceptible to infections with several species of Plasmodium, including the predecessor of Plasmodium falciparum. Little is known about the ecology of these pathogens in gorillas. A total of 131 gorilla fecal samples were collected from Dzanga-Sangha Protected Areas to study the diversity and prevalence of Plasmodium species. The effects of sex and age as factors influencing levels of infection with Plasmodium in habituated gorilla groups were assessed. Ninety-five human blood samples from the same locality were also analysed to test for cross-transmission between humans and gorillas. According to a cytB PCR assay 32% of gorilla's fecal samples and 43·1% human individuals were infected with Plasmodium spp. All Laverania species, Plasmodium vivax, and for the first time Plasmodium ovale were identified from gorilla samples. Plasmodium praefalciparum was present only from habituated individuals and P. falciparum was detected from human samples. Although few P. vivax and P. ovale sequences were obtained from gorillas, the evidence for cross-species transmission between humans and gorillas requires more in depth analysis. No association was found between malaria infection and sex, however, younger individuals aged ≤6 years were more susceptible. Switching between two different Plasmodium spp. was observed in three individuals. Prolonged monitoring of Plasmodium infection during various seasons and recording behavioural data is necessary to draw a precise picture about the infection dynamics.
We report the first record of the sea anemone Bunodosoma californicum on the Pacific coast of Costa Rica, extending its southern distribution. Four specimens were collected from an artificial breakwater in Mata de Limón, Puntarenas. We present images of the live specimens and analyses of their cnidae composition.
Superbubbles and large scale expansion in galaxies are important indicators of activity in galaxies: they are formed in starbursts and around active nuclei. Superbubbles can be used to give information about the star-forming region which produced them. We present in-depth results of our study of kinematically detected superbubbles using a method based on Fabry-Perot spectroscopy, which allows us to map regions of expansion across the entire disk of a galaxy. Three objects have been selected for this poster based on the interest of the results they show: two interacting galaxies, the Antennae and Arp270, at different stages of galaxy interaction, and the more isolated galaxy M83. We present the kinematic expansion maps, as well as a census of detected superbubbles and a dynamical study of their properties.
Networks of protected areas are one of the main strategies used to address the biodiversity crisis. These should encompass as many species and ecosystems as possible, particularly in territories with high biological diversity, such as the Spanish arid zones. We produce a priority ranking of the arid zones of south-east Spain according to the rarity and richness of their characteristic flora and the level of endangerment. The resulting hierarchy shows that optimal zones for the preservation of the flora are located outside the network of protected areas. In particular, it is important to extend the network and encourage the creation of microreserves in the depression of the River Guadiana Menor (Granada), where there is least protection. This river valley is a particularly important arid site because of its unique flora and fauna, and palaeontological and archaeological findings.