436 research outputs found

    Primate proteomic composition of seminal plasma and prostate-specific transglutaminase activity in relation to sexual selection.

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    Humans (Homo sapiens), chimpanzees (Pan troglodytes), and gorillas (Gorilla gorilla) have diverse mating systems with varying levels of sperm competition. Several seminal plasma genes have been claimed to evolve under positive selection, while others are altered or lost. This study aims to identify biologically relevant differences among seminal plasma proteomes of primates in relation to mating systems and previous genomic studies. Seminal plasma from three individuals of each species were run in triplicate in shotgun liquid chromatography – tandem mass spectrometry (LC-MS/MS) and confirmed with Western blots. Over 7,000 peptides were identified across all individuals; 168 proteins were identified with high confidence, 70 seminal plasma proteins were identified for human, 64 proteins for chimpanzee, and 34 proteins for gorilla. The gorilla seminal plasma proteome has higher variation among individuals and many proteins involved in semen coagulation and liquefaction have been lost. Chimpanzees have approximately 7-fold higher prostate specific transglutaminase (TGM4) expression than humans. TGM4 was not detected in gorillas, supporting pseudogenization of this gene. The structural semenogelin proteins, SEMG1 and SEMG2, were detected in high abundance in only one of three gorilla individuals, and in all three human and chimpanzee individuals. Chimpanzees have significantly higher expression of SEMG1 (~2.5-fold) compared to human; whereas, they only produce a small amount of SEMG2; ~6.5 –fold less than humans. Chimpanzees have roughly 34-fold higher expression of a serine protease inhibitor, SERPINA3 (Serpin Family A Member 3), than humans. SERPINA3 paralogs, SERPINA1 and SERPINA5, also have increased expression (~2.5 –fold) compared to human, and only SERPINA1 was detected in gorilla. SERPINAs may delay protease dissolution of the copulatory plug in chimpanzees. Recombinant human TGM4 and the reconstructed ancestral TGM4 sequence of our last common ancestor (LCA) with chimpanzees (the human-chimpanzee ancestor) proteins were produced and incubated with casein and monodansylcaverdine to determine enzymatic activity. The human-chimpanzee ancestor TGM4 had higher activity compared to human TGM4. Considering the importance of TGM4 in semen coagulation and copulatory plug formation in chimpanzee, the increased activity of the human-chimpanzee ancestor TGM4 may be indicative of elevated female promiscuity of our LCA, perhaps similar to a chimp-like mating system

    Asthma und Allergien bei Kindern : Ursachen, Konsequenzen, Therapiestrategien

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    Die Häufigkeitsrate atopischer Erkrankungen bei Kindern, wie Heuschnupfen, Asthma, Neurodermitis (atopische Dermatitis), nimmt weltweit zu. Die Gründe sind vielschichtig. Gesichert ist der Zusammenhang zwischen der erblichen Überempfindlichkeit gegenüber natürlichen Substanzen (Atopie) und vermehrter Allergen- und Passivrauch-Exposition sowie Zunahme der Ein-Kind-Familien, Veränderung der mikrobiologischen Besiedlung des Darmes und Infektexposition. Besonders gut untersucht wurden diese Zusammenhänge von Erika von Mutius in einer Studie, in der sie von 1991 bis 1992 die Häufigkeit von Asthma in München (5030 Kinder) und Leipzig/Bitterfeld (2623 Kinder) verglichen hat

    Airway responses and inflammation in subjects with asthma after four days of repeated high-single-dose allergen challenge

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    Background: Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation. Methods: A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days. Pulmonary function and exhaled NO were measured at every visit. Induced sputum was analysed before and after the allergen challenges for cell counts, ECP, IL-5, INF-γ, IL-8, and the transcription factor Foxp3. Results: We found a significant decrease in pulmonary function, an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness, as well as a significant induction of eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the majority of patients. Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms. Conclusions: Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation. The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations. Trial registration: ClinicalTrials.govNCT0067720

    An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine

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    BACKGROUND: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron(R)) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, polio, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. METHODS: Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6--8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. RESULTS: In the intent-to-treat population, paracetamol reduced the incidence of fever >=38[degree sign]C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39[degree sign]C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39[degree sign]C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. CONCLUSIONS: Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis.Trial registration: NCT00294294

    Factorised Steady States in Mass Transport Models

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    We study a class of mass transport models where mass is transported in a preferred direction around a one-dimensional periodic lattice and is globally conserved. The model encompasses both discrete and continuous masses and parallel and random sequential dynamics and includes models such as the Zero-range process and Asymmetric random average process as special cases. We derive a necessary and sufficient condition for the steady state to factorise, which takes a rather simple form.Comment: 6 page

    Matrix product approach for the asymmetric random average process

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    We consider the asymmetric random average process which is a one-dimensional stochastic lattice model with nearest neighbour interaction but continuous and unbounded state variables. First, the explicit functional representations, so-called beta densities, of all local interactions leading to steady states of product measure form are rigorously derived. This also completes an outstanding proof given in a previous publication. Then, we present an alternative solution for the processes with factorized stationary states by using a matrix product ansatz. Due to continuous state variables we obtain a matrix algebra in form of a functional equation which can be solved exactly.Comment: 17 pages, 1 figur
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