203 research outputs found
Branch Mode Selection during Early Lung Development
Many organs of higher organisms, such as the vascular system, lung, kidney,
pancreas, liver and glands, are heavily branched structures. The branching
process during lung development has been studied in great detail and is
remarkably stereotyped. The branched tree is generated by the sequential,
non-random use of three geometrically simple modes of branching (domain
branching, planar and orthogonal bifurcation). While many regulatory components
and local interactions have been defined an integrated understanding of the
regulatory network that controls the branching process is lacking. We have
developed a deterministic, spatio-temporal differential-equation based model of
the core signaling network that governs lung branching morphogenesis. The model
focuses on the two key signaling factors that have been identified in
experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well
as the SHH receptor patched (Ptc). We show that the reported biochemical
interactions give rise to a Schnakenberg-type Turing patterning mechanisms that
allows us to reproduce experimental observations in wildtype and mutant mice.
The kinetic parameters as well as the domain shape are based on experimental
data where available. The developed model is robust to small absolute and large
relative changes in the parameter values. At the same time there is a strong
regulatory potential in that the switching between branching modes can be
achieved by targeted changes in the parameter values. We note that the sequence
of different branching events may also be the result of different growth
speeds: fast growth triggers lateral branching while slow growth favours
bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is
sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio
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Novel European free-living, non-diazotrophic Bradyrhizobium isolates from contrasting soils that lack nodulation and nitrogen fixation genes - a genome comparison
The slow-growing genus Bradyrhizobium is biologically important in soils, with different representatives
found to perform a range of biochemical functions including photosynthesis, induction of root nodules
and symbiotic nitrogen fixation and denitrification. Consequently, the role of the genus in soil ecology
and biogeochemical transformations is of agricultural and environmental significance. Some isolates of
Bradyrhizobium have been shown to be non-symbiotic and do not possess the ability to form nodules.
Here we present the genome and gene annotations of two such free-living Bradyrhizobium isolates,
named G22 and BF49, from soils with differing long-term management regimes (grassland and bare
fallow respectively) in addition to carbon metabolism analysis. These Bradyrhizobium isolates are
the first to be isolated and sequenced from European soil and are the first free-living Bradyrhizobium
isolates, lacking both nodulation and nitrogen fixation genes, to have their genomes sequenced and
assembled from cultured samples. The G22 and BF49 genomes are distinctly different with respect
to size and number of genes; the grassland isolate also contains a plasmid. There are also a number
of functional differences between these isolates and other published genomes, suggesting that this
ubiquitous genus is extremely heterogeneous and has roles within the community not including
symbiotic nitrogen fixation
A randomized controlled multicenter trial of post-suicide attempt case management for the prevention of further attempts in Japan (ACTION-J)
<p>Abstract</p> <p>Background</p> <p>A previous suicide attempt is a potent risk factor for suicide later on. Crisis intervention, psychiatric and psychosocial evaluation at emergency medical facilities, and follow-up care for suicide attempters are considered important components for suicide prevention. The Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) includes a randomized, controlled, multicenter trial of post-suicide attempt case management for the prevention of further attempts (ACTION-J) to address the continuing increase in suicides in Japan. The primary aim of ACTION-J is to examine the effectiveness of an extensive intervention for suicide attempters in prevention of recurrent suicidal behavior, as compared with standard intervention. This paper describes the rationale and protocol of the ACTION-J trial.</p> <p>Methods/Design</p> <p>In this clinical trial, case management intervention will be provided at 19 emergency medical facilities in Japan. After crisis intervention including psychiatric evaluation, psychosocial assessment, and psychological education, subjects will be randomly assigned to either a group receiving continuous case management or a control group receiving standard care. Suicidal ideation, depressive symptoms, and general health condition will be evaluated as secondary measures. The intervention was initiated in July 2006. By December, 2009, 842 subjects will be randomized. Subject follow-up will continue for 1.5 to 5 years.</p> <p>Discussion</p> <p>Suicide is a complex phenomenon that encompasses multiple factors. Case management by multi-sector collaboration is needed. ACTION-J may provide valuable information on suicide attempters and may develop effective case management to reduce future risk for suicide attempters.</p> <p>Trial registration</p> <p>UMIN Clinical Trials Registry number, UMIN000000444. ClinicalTrials.gov number, NCT00736918.</p
The prevalence of hypertension, obesity and dyslipidemia in individuals of over 30 years of age belonging to minorities from the pasture area of Xinjiang
<p>Abstract</p> <p>Background</p> <p>The prevalence of population-wide hypertension, obesity and dyslipidemia has not been well studied in the pasture area of Xinjiang. The present epidemiological study was performed to determine the prevalence of hypertension, obesity and dyslipidemia in minority populations from the pasture area of Xinjiang and to discuss the potential risk factors for hypertension.</p> <p>Methods</p> <p>A population-based, cross-sectional study in the Xinjiang pasture area was performed which included 2251 participants aged over 30 years (90.33% participation rate) of whom 71.26% were Kazaks. Several risk factors were considered: hypertension (defined as systolic or diastolic blood pressure or both of at least 140/90 mmHg measured on one occasion or treatment for hypertension) overweight/obesity (body mass index β₯ 25 kg/m<sup>2</sup>) alcohol intake, smoking/tobacco use and dyslipidemia. Outcomes were prevalence of hypertension, obesity and dyslipidemia and the associated risk factors of hypertension detected by multivariate logistic regression analysis taking into account various metabolic and lifestyle characteristics.</p> <p>Results</p> <p>The prevalence of hypertension, overweight/obesity and dyslipidemia in all participants from the pasture area of Xinjiang was 51.9%, 47.9% and 49.2% respectively. Independently, the prevalence and awareness of hypertension was 52.6% and 15.3% among Kazaks (n = 1604), 54.6% and 14.1% among Uygurs (n = 418), 39.5% and 16.1% among Mongolians (n = 81) and 43.9% and 18.2% among non-Xinjiang-born Han immigrants (n = 148). The prevalence of overweight/obesity in Kazaks, Uygurs, Mongolians and Han immigrants was 46.7%, 48.9%, 62.5% and 50.3%, respectively. The prevalence of dyslipidemia in the four ethnic groups mentioned was 53.5%, 34.8%, 49.3% and 47.3%, respectively. The mean blood pressure in all participants was 136/86 mmHg (pre-hypertensive), the mean BMI was 24.7 kg/m<sup>2</sup>. Based on multiple logistic regression analysis, the significant risk factors for hypertension were age [1.07(1.06-1.09), P < 0.0001], overweight/obesity [overweight: 1.61(1.22-2.13), p = 0.0007; obesity: 1.95 (1.33-2.87), p = 0.0007], hypercholesterolemia [1.30(1.15-1.47), p < 0.0001] and an alcohol intake of over 30 g/day [2.22(1.43-3.45), p = 0.0004].</p> <p>Conclusions</p> <p>The considerably high prevalence of hypertension, overweight/obesity and dyslipidemia among the minority population aged over 30 from the pasture area of Xinjiang calls for effective preventive measures. Age, increased body mass index, hypercholesterolemia and β₯30 g/d alcohol intake can be counted as risk factors for hypertension, but further genetic or environmental clarification would be desirable to explain the unusually high prevalence of the conditions mentioned above.</p
Comparative Analysis of Expressed Sequence Tag (EST) Libraries in the Seagrass Zostera marina Subjected to Temperature Stress
Global warming is associated with increasing stress and mortality on temperate seagrass beds, in particular during periods of high sea surface temperatures during summer months, adding to existing anthropogenic impacts, such as eutrophication and habitat destruction. We compare several expressed sequence tag (EST) in the ecologically important seagrass Zostera marina (eelgrass) to elucidate the molecular genetic basis of adaptation to environmental extremes. We compared the tentative unigene (TUG) frequencies of libraries derived from leaf and meristematic tissue from a control situation with two experimentally imposed temperature stress conditions and found that TUG composition is markedly different among these conditions (all Pβ<β0.0001). Under heat stress, we find that 63 TUGs are differentially expressed (d.e.) at 25Β°C compared with lower, no-stress condition temperatures (4Β°C and 17Β°C). Approximately one-third of d.e. eelgrass genes were characteristic for the stress response of the terrestrial plant model Arabidopsis thaliana. The changes in gene expression suggest complex photosynthetic adjustments among light-harvesting complexes, reaction center subunits of photosystem I and II, and components of the dark reaction. Heat shock encoding proteins and reactive oxygen scavengers also were identified, but their overall frequency was too low to perform statistical tests. In all conditions, the most abundant transcript (3β15%) was a putative metallothionein gene with unknown function. We also find evidence that heat stress may translate to enhanced infection by protists. A total of 210 TUGs contain one or more microsatellites as potential candidates for gene-linked genetic markers. Data are publicly available in a user-friendly database at http://www.uni-muenster.de/Evolution/ebb/Services/zostera
Regulation of GSK-3 Activity as A Shared Mechanism in Psychiatric Disorders
Serin/Treonin kinaz ailesinin ΓΌyelerinden bir kinaz olarak ilk kez glikojen sentazβΔ± inhibe ettiΔi keΕfedilen glikojen sentaz kinaz-3 (GSK-3), gΓΌnΓΌmΓΌzde bilinen 50βden fazla substratΔ± ile birΓ§ok hΓΌcre iΓ§i dΓΌzenleyici mekanizmada gΓΆrev alan geniΕ etki spektrumlu bir enzim olarak kabul edilmektedir. GSK-3βΓΌn memelilerde GSK-3Ξ± ve GSK-3Ξ² olmak ΓΌzere yapΔ±sal olarak yΓΌksek homoloji gΓΆsteren iki izoformu bulunmaktadΔ±r. Her iki izoform birΓ§ok dokuda yaygΔ±n daΔΔ±lΔ±m gΓΆstermekle beraber, en yΓΌksek oranda beyinde bulunmakta ve genellikle benzer fonksiyonlar gΓΆstermektedirler. DiΔer protein kinazlarΔ±n aksine GSK-3 uyarΔ±lmamΔ±Ε hΓΌcrede yapΔ±sal olarak aktif yani defosforile halde bulur. Protein kinaz A (PKA), protein kinaz B (PKB;AKT) ve protein kinaz C (PKC) gibi diΔer protein kinazlarla fosforilasyona uΔrayarak olarak inaktive edilir. GΓΌnΓΌmΓΌzde artmΔ±Ε GSK-3 aktivitesinin major depresyon, bipolar bozukluk, hiperaktivite bozukluklarΔ± gibi hastalΔ±klar ve Εizofreni oluΕumunda rol oynayabileceΔine iliΕkin ΓΆnemli bulgular mevcuttur. Bu nedenle sΓΆz konusu psikiyatrik hastalΔ±klarda arttΔ±ΔΔ± gΓΆsterilen GSK-3 aktivitesinin azaltΔ±lmasΔ±nΔ±n tedavide umut verici bir yaklaΕΔ±m olabileceΔi kabul edilebilir. Bu gΓΆzden geΓ§irme Γ§alΔ±ΕmasΔ±nda yukarΔ±da sΓΆzΓΌ edilen psikiyatrik hastalΔ±klarΔ±n oluΕmasΔ±nda gΓΆrev alan GSK-3 aracΔ±lΔ± mekanizmalara kΔ±saca deΔinilerek GSK-3βΓΌn aktivitesinin dΓΌzenlenmesinde rol oynadΔ±ΔΔ± gΓΆsterilen klinikte kullanΔ±lan ilaΓ§lara yer verilmiΕtir. Anahtar sΓΆzcΓΌkler: GSK-3, depresyon, bipolar bozukluk, Εizofren
Evaluation of an Antimicrobial L-Amino Acid Oxidase and Peptide Derivatives from Bothropoides mattogrosensis Pitviper Venom
Healthcare-associated infections (HAIs) are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO) is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO) was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3) were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms
Molecular psychiatry of zebrafish
Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research
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