Stimulation of the pituitary-adrenal axis with arginine vasopressin in patients with depression

The ACTH response to arginine vasopressin was the same in patients with depression while cortisol response was significantly greater in patients with depression when compared to the control population. These findings are consistent with the hypothesis that vasopressin corticotroph receptors are not downregulated in depression and that there is increased adrenal responsiveness in patients with depression to endogenous ACTH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26928/1/0000494.pd

Multiple steroid hormone levels in depressed patients and normal controls before and after exogenous ACTH

Forty depressed patients and 36 age- and sex-matched controls were given 250 [mu]g ACTH1-24 by bolus. Plasma steroid hormone levels were measured prior to and 60 min after ACTH administration. The depressed patients had significantly greater cortisol (F), 11-deoxycortisol (S), androstenedione (AD), and 17[alpha]-hydroxyprogesterone (17[alpha]-OHP) responses (delta; pp=0.091) than the controls. There was no significant difference in the corticosterone (B) response between the two groups.With the exception of 11[beta]-OHAD, all the steroid hormones were significantly negatively correlated with age in the controls, but only S and AD marginally demonstrated this relationship in the depressed patients. F, S, AD, 17[alpha]-OHP, and B, but not 11[beta]-OHAD, were significantly positively correlated with each other in the controls, but only F was significantly correlated with AD in the depressed patients. These data suggest that the hypercortisolemia found in some depressed patients involves increased precursor and metabolite levels both at baseline and in response to exogenous ACTH, compared to controls. Furthermore, variability in these precursors is greater in depressed patients, and their relationship to age is lost. These findings are consistent with the hypothesis that adrenal products other than cortisol also could be related to affective symptoms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29624/1/0000713.pd

Autoregulation of the Drosophila Noncoding roX1 RNA Gene

Most genes along the male single X chromosome in Drosophila are hypertranscribed about two-fold relative to each of the two female X chromosomes. This is accomplished by the MSL (male-specific lethal) complex that acetylates histone H4 at lysine 16. The MSL complex contains two large noncoding RNAs, roX1 (RNA on X) and roX2, that help target chromatin modifying enzymes to the X. The roX RNAs are functionally redundant but differ in size, sequence, and transcriptional control. We wanted to find out how roX1 production is regulated. Ectopic DC can be induced in wild-type (roX1+ roX2+) females if we provide a heterologous source of MSL2. However, in the absence of roX2, we found that roX1 expression failed to come on reliably. Using an in situ hybridization probe that is specific only to endogenous roX1, we found that expression was restored if we introduced either roX2 or a truncated but functional version of roX1. This shows that pre-existing roX RNA is required to positively autoregulate roX1 expression. We also observed massive cis spreading of the MSL complex from the site of roX1 transcription at its endogenous location on the X chromosome. We propose that retention of newly assembled MSL complex around the roX gene is needed to drive sustained transcription and that spreading into flanking chromatin contributes to the X chromosome targeting specificity. Finally, we found that the gene encoding the key male-limited protein subunit, msl2, is transcribed predominantly during DNA replication. This suggests that new MSL complex is made as the chromatin template doubles. We offer a model describing how the production of roX1 and msl2, two key components of the MSL complex, are coordinated to meet the dosage compensation demands of the male cell

Ancient DNA from European Early Neolithic Farmers Reveals Their Near Eastern Affinities

The first farmers from Central Europe reveal a genetic affinity to modern-day populations from the Near East and Anatolia, which suggests a significant demographic input from this area during the early Neolithic

A review of Monte Carlo simulations of polymers with PERM

In this review, we describe applications of the pruned-enriched Rosenbluth method (PERM), a sequential Monte Carlo algorithm with resampling, to various problems in polymer physics. PERM produces samples according to any given prescribed weight distribution, by growing configurations step by step with controlled bias, and correcting "bad" configurations by "population control". The latter is implemented, in contrast to other population based algorithms like e.g. genetic algorithms, by depth-first recursion which avoids storing all members of the population at the same time in computer memory. The problems we discuss all concern single polymers (with one exception), but under various conditions: Homopolymers in good solvents and at the $\Theta$ point, semi-stiff polymers, polymers in confining geometries, stretched polymers undergoing a forced globule-linear transition, star polymers, bottle brushes, lattice animals as a model for randomly branched polymers, DNA melting, and finally -- as the only system at low temperatures, lattice heteropolymers as simple models for protein folding. PERM is for some of these problems the method of choice, but it can also fail. We discuss how to recognize when a result is reliable, and we discuss also some types of bias that can be crucial in guiding the growth into the right directions.Comment: 29 pages, 26 figures, to be published in J. Stat. Phys. (2011

A new strategy for isolating genes controlling dosage compensation in Drosophila using a simple epigenetic mosaic eye phenotype

<p>Abstract</p> <p>Background</p> <p>The <it>Drosophila </it>Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and non-coding <it>roX </it>RNA. It paints the male X at hundreds of bands where it acetylates histone H4 at lysine 16. This epigenetic mark increases expression from the single male X chromosome approximately twofold above what gene-specific factors produce from each female X chromosome. This equalises X-linked gene expression between the sexes. Previous screens for components of dosage compensation relied on a distinctive male-specific lethal phenotype.</p> <p>Results</p> <p>Here, we report a new strategy relying upon an unusual male-specific mosaic eye pigmentation phenotype produced when the MSL complex acts upon autosomal <it>roX1 </it>transgenes. Screening the second chromosome identified at least five loci, two of which are previously described components of the MSL complex. We focused our analysis on the modifier alleles of MSL1 and MLE (for 'maleless'). The MSL1 lesions are not simple nulls, but rather alter the PEHE domain that recruits the MSL3 chromodomain and MOF ('males absent on first') histone acetyltransferase subunits to the complex. These mutants are compromised in their ability to recruit MSL3 and MOF, dosage compensate the X, and support long distance spreading from <it>roX1 </it>transgenes. Yet, paradoxically, they were isolated because they somehow increase MSL complex activity immediately around <it>roX1 </it>transgenes in combination with wild-type MSL1 subunits.</p> <p>Conclusions</p> <p>We propose that these diverse phenotypes arise from perturbations in assembly of MSL subunits onto nascent <it>roX </it>transcripts. This strategy is a promising alternative route for identifying previously unknown components of the dosage compensation pathway and novel alleles of known MSL proteins.</p

Elevated Serum Levels of Interferon-Regulated Chemokines Are Biomarkers for Active Human Systemic Lupus Erythematosus

BACKGROUND: Systemic lupus erythematosus (SLE) is a serious systemic autoimmune disorder that affects multiple organ systems and is characterized by unpredictable flares of disease. Recent evidence indicates a role for type I interferon (IFN) in SLE pathogenesis; however, the downstream effects of IFN pathway activation are not well understood. Here we test the hypothesis that type I IFN-regulated proteins are present in the serum of SLE patients and correlate with disease activity. METHODS AND FINDINGS: We performed a comprehensive survey of the serologic proteome in human SLE and identified dysregulated levels of 30 cytokines, chemokines, growth factors, and soluble receptors. Particularly striking was the highly coordinated up-regulation of 12 inflammatory and/or homeostatic chemokines, molecules that direct the movement of leukocytes in the body. Most of the identified chemokines were inducible by type I IFN, and their levels correlated strongly with clinical and laboratory measures of disease activity. CONCLUSIONS: These data suggest that severely disrupted chemokine gradients may contribute to the systemic autoimmunity observed in human SLE. Furthermore, the levels of serum chemokines may serve as convenient biomarkers for disease activity in lupus

Методические указания к выполнению индивидуальных заданий практикума по дисциплине «Энергетический потенциал природных возобновляемых энергоресурсов и эффективность его преобразования в электроэнергию»

В методических указаниях рассмотрены вопросы оценки энергетического потенциала природных возобновляемых энергоресурсов: ветра, солнечного излучения и потоков воды и эффективности их преобразования в электроэнергию. Пособие предназначено для студентов дневного обучения по направлению13.04.02 «Электроэнергетика и электротехника» по профилям магистерской подготовки «Возобновляемые источники энергии» и «Оптимизация развивающихся систем электроснабжения»

Urban Air Mobility Research at the DLR German Aerospace Center - Getting the HorizonUAM Project Started

Efficiency, safety, feasibility, sustainability and affordability are among the key characteristics of future urban mobility. The project “HorizonUAM - Urban Air Mobility Research at the German Aerospace Center (DLR)” provides first answers to this vision by pooling existing competencies of individual institutes within DLR. HorizonUAM combines research about urban air mobility (UAM) vehicles, the corresponding infrastructure, the operation of UAM services, as well as public acceptance and market development of future urban air transportation. Competencies and current research topics including propulsion technologies, flight system technologies, communication and navigation go along in conjunction with the findings of modern flight guidance and airport technology techniques. The project analyses possible UAM market scenarios up to the year 2050 and assesses economic aspects such as the degree of vehicle utilization or cost-benefit potential via an overall system model. Furthermore, the system design for future air taxis is carried out on the basis of vehicle family concepts, onboard systems, aspects of safety and security as well as the certification of autonomy functions. The analysis of flight guidance concepts and the sequencing of air taxis at vertidromes is another central part of the project. Selected concepts for flight guidance, communication and navigation technology will also be demonstrated with drones in a scaled urban scenario. This paper gives an overview of the topics covered in the HorizonUAM project, running from mid-2020 to mid-2023, as well as an early progress report

Chile's export diversification since 1960: A free market miracle or mirage?

Conventional wisdom has proclaimed Chile's recent economic development a 'free market miracle'. In an examination of Chile's export diversification experience, this article departs from that view. By analysing the dynamics underlying the emergence of the salmon, fruit, forestry and wine sectors in Chile's export basket since the 1960s, the study sheds light on the crucial role of industrial policy in the process of capability accumulation that shapes new industries. The article undertakes a qualitative historical analysis of the scope and nature of policy interventions in each of the four sectors and conducts a quantitative policy evaluation using the difference-in-difference method. It finds that public institutions are essential in overcoming market failures inhibiting the emergence of new industries. Specifically, it shows that the government has a key role to play as a catalyst of human capital accumulation, as a venture capitalist, in trade promotion, and in ensuring 'national' sector reputation through a strong regulatory and quality control role. By elaborating on the dynamic process of structural transformation and capability accumulation, this article contributes to theoretical debates on the role of vertical policies in the emergence of new competitive sectors, and debates relating to static versus dynamic approaches to comparative advantage