bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial Estrogen Receptor-α Does Not Protect Against Vascular Stiffness Induced by Western Diet in Female Mice
Authors: Manrique Camila , Lastra Guido , Ramirez-Perez Francisco I. , Haertling Dominic , DeMarco Vincent G. , Aroor Annayya R. , Jia Guanghong , Chen Dongqing , Barron Brady J. , Garro Mona , Padilla Jaume , Martinez-Lemus Luis A. , Sowers James R. 
Published: February 2016

AbstractConsumption of a diet high in fat and refined carbohydrates (Western diet [WD]) is associated with obesity and insulin resistance, both major risk factors for cardiovascular disease (CVD). In women, obesity and insulin resistance abrogate the protection against CVD likely afforded by estrogen signaling through estrogen receptor (ER)α. Indeed, WD in females results in increased vascular stiffness, which is independently associated with CVD. We tested the hypothesis that loss of ERα signaling in the endothelium exacerbates WD-induced vascular stiffening in female mice. We used a novel model of endothelial cell (EC)-specific ERα knockout (EC-ERαKO), obtained after sequential crossing of the ERα double floxed mice and VE-Cadherin Cre-recombinase mice. Ten-week-old females, EC-ERαKO and aged-matched genopairs were fed either a regular chow diet (control diet) or WD for 8 weeks. Vascular stiffness was measured in vivo by pulse wave velocity and ex vivo in aortic explants by atomic force microscopy. In addition, vascular reactivity was assessed in isolated aortic rings. Initial characterization of the model fed a control diet did not reveal changes in whole-body insulin sensitivity, aortic vasoreactivity, or vascular stiffness in the EC-ERαKO mice. Interestingly, ablation of ERα in ECs reduced WD-induced vascular stiffness and improved endothelial-dependent dilation. In the setting of a WD, endothelial ERα signaling contributes to vascular stiffening in females. The precise mechanisms underlying the detrimental effects of endothelial ERα in the setting of a WD remain to be elucidated.
Comparative Assessment of Female Mouse Model of Graves' Orbitopathy Under Different Environments, Accompanied by Proinflammatory Cytokine and T-Cell Responses to Thyrotropin Hormone Receptor Antigen
Authors: Berchner-Pfannschmidt Utta , Moshkelgosha Sajad , Diaz-Cano Salvador , Edelmann Bärbel , Görtz Gina-Eva , Horstmann Mareike , Noble Alistair , Hansen Wiebke , Eckstein Anja , Banga J. Paul 
Published: February 2016

Abstract
We recently described a preclinical model of Graves' orbitopathy (GO), induced by genetic immunization of eukaryotic expression plasmid encoding human TSH receptor (TSHR) A-subunit by muscle electroporation in female BALB/c mice. The onset of orbital pathology is characterized by muscle inflammation, adipogenesis, and fibrosis. Animal models of autoimmunity are influenced by their environmental exposures. This follow-up study was undertaken to investigate the development of experimental GO in 2 different locations, run in parallel under comparable housing conditions. Functional antibodies to TSHR were induced in TSHR A-subunit plasmid-immunized animals, and antibodies to IGF-1 receptor α-subunit were also present, whereas control animals were negative in both locations. Splenic T cells from TSHR A-subunit primed animals undergoing GO in both locations showed proliferative responses to purified TSHR antigen and secreted interferon-γ, IL-10, IL-6, and TNF-α cytokines. Histopathological evaluation showed orbital tissue damage in mice undergoing GO, manifest by adipogenesis, fibrosis, and muscle damage with classic signs of myopathy. Although no inflammatory infiltrate was observed in orbital tissue in either location, the appearances were consistent with a “hit-and-run” immune-mediated inflammatory event. A statistically significant increase of cumulative incidence of orbital pathology when compared with control animals was shown for both locations, confirming onset of orbital dysimmune myopathy. Our findings confirm expansion of the model in different environments, accompanied with increased prevalence of T cell-derived proinflammatory cytokines, with relevance for pathogenesis. Wider availability of the model makes it suitable for mechanistic studies into pathogenesis and undertaking of novel therapeutic approaches.
The Parkinson's-disease-associated receptor GPR37 undergoes metalloproteinase-mediated N-terminal cleavage and ectodomain shedding
Authors: Mattila S. Orvokki , Tuusa Jussi T. , Petäjä-Repo Ulla E. 
Published: February 2016

ABSTRACT
The G-protein-coupled receptor 37 ( GPR37) has been implicated in the juvenile form of Parkinson's disease, in dopamine signalling and in the survival of dopaminergic cells in animal models. The structure and function of the receptor, however, have remained enigmatic. Here, we demonstrate that although GPR37 matures and is exported from the endoplasmic reticulum in a normal manner upon heterologous expression in HEK293 and SH-SY5Y cells, its long extracellular N-terminus is subject to metalloproteinase-mediated limited proteolysis between E167 and Q168. The proteolytic processing is a rapid and efficient process that occurs constitutively. Moreover, the GPR37 ectodomain is released from cells by shedding, a phenomenon rarely described for GPCRs. Immunofluorescence microscopy further established that although full-length receptors are present in the secretory pathway until the trans-Golgi network, GPR37 is expressed at the cell surface predominantly in the N-terminally truncated form. This notion was verified by flow cytometry and cell surface biotinylation assays. These new findings on the GPR37 N-terminal limited proteolysis may help us to understand the role of this GPCR in the pathophysiology of Parkinson's disease and in neuronal function in general.
CAPS1 effects on intragranular pH and regulation of BDNF release from secretory granules in hippocampal neurons
Authors: Eckenstaler Robert , Lessmann Volkmar , Brigadski Tanja 
Published: February 2016

ABSTRACT
The secretory protein brain-derived neurotrophic factor (BDNF) is assumed to be a key factor for the induction of synaptic plasticity processes in neurons. However, the molecular mechanisms for activity-dependent release of the protein largely remain elusive. Here, we demonstrate the relevance of the priming factor CAPS1 (also known as CADPS) for the maturation and exocytosis of BDNF-containing secretory granules, as well as for neurotransmitter release from synaptic vesicles. Using live-cell imaging and RNA silencing methods, we show that CAPS1 has a previously unrecognized function in regulating the intragranular pH of BDNF-containing secretory granules. Furthermore, our results demonstrate that acute single-cell knockdown of CAPS1 with unaltered expression in neighboring neurons leads to a strong reduction in the number of fusion-competent secretory granules and to a significant decrease of released BDNF following exocytosis in dendrites of CAPS1-deficient neurons. In addition, our results show a reduction in synaptic vesicle turnover after CAPS1 knockdown without affecting the density of active boutons in hippocampal neurons. Thus, our results reveal new functions of endogenous CAPS1 in the BDNF secretory granule life cycle, thereby representing a new mechanism of neuronal plasticity.
Suppression of microtubule assembly kinetics by the mitotic protein TPX2
Authors: Reid Taylor A. , Schuster Breanna M. , Mann Barbara J. , Balchand Sai Keshavan , Plooster Melissa , McClellan Mark , Coombes Courtney E. , Wadsworth Pat , Gardner Melissa K. 
Published: February 2016

ABSTRACT
TPX2 is a widely conserved microtubule-associated protein that is required for mitotic spindle formation and function. Previous studies have demonstrated that TPX2 is required for the nucleation of microtubules around chromosomes; however, the molecular mechanism by which TPX2 promotes microtubule nucleation remains a mystery. In this study, we found that TPX2 acts to suppress tubulin subunit off-rates during microtubule assembly and disassembly, thus allowing for the support of unprecedentedly slow rates of plus-end microtubule growth, and also leading to a dramatically reduced microtubule shortening rate. These changes in microtubule dynamics can be explained in computational simulations by a moderate increase in tubulin–tubulin bond strength upon TPX2 association with the microtubule lattice, which in turn acts to reduce the departure rate of tubulin subunits from the microtubule ends. Thus, the direct suppression of tubulin subunit off-rates by TPX2 during microtubule growth and shortening could provide a molecular mechanism to explain the nucleation of new microtubules in the presence of TPX2.
Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis
Authors: Takemoto Ai , Kawashima Shigehiro A. , Li Juan-Juan , Jeffery Linda , Yamatsugu Kenzo , Elemento Olivier , Nurse Paul 
Published: February 2016

ABSTRACT
Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation.
18F-FDG PET/CT imaging and PET-guided biopsy in evaluation and treatment decision in adrenal histoplasmosis
Authors: Kalathoorakath Renjith Radhakrishnan , Sharma Aman , Sood Ashwani , Nahar Uma , Gorla Arun Kumar Reddy , Mittal Bhagwant Rai 
Published: February 2016

Abstract
Histoplasmosis is a rare opportunistic fungal infection. It is commonly seen in immunocompromised individuals from endemic areas. Adrenal glands are frequently involved in the disseminated disease. Here, we present the case of a retropositive patient with constitutional symptoms, where whole-body positron emission tomography/CT scan revealed intense 18F-fludeoxyglucose uptake in bulky adrenal glands, and subsequent positron emission tomography-guided biopsy helped in establishing the diagnosis of adrenal histoplasmosis.
Understanding the nature of health: New perspectives for medicine and public health. Improved wellbeing at lower costs
Authors: Bircher Johannes , Hahn Eckhart G. 
Published: February 2016

Background: Current dilemmas of health care systems call for a new look at the nature of health. This is offered by the Meikirch model. We explore its hypothetical benefit for the future of medicine and public health.Meikirch model: It states: “Health is a dynamic state of wellbeing emergent from conducive interactions between individuals’ potentials, life’s demands, and social and environmental determinants.” “Throughout the life course health results when an individuals’ biologically given potential (BGP) and his or her personally acquired potential (PAP), interacting with social and environmental determinants, satisfactorily respond to the demands of life.”Methods: We explored the Meikirch model’s possible applications for personal and public health care.Results: The PAP of each individual is the most modifiable component of the model. It responds to constructive social interactions and to personal growth. If an individual’s PAP is nurtured to develop further, it likely will contribute much more to health than without fostering. It may also compensate for losses of the BGP. An ensuing new culture of health may markedly improve health in the society. The rising costs of health care presumably are due in part to the tragedy of the commons and to moral hazard. Health as a complex adaptive system offers new possibilities for patient care, particularly for general practitioners.Discussion: Analysis of health systems by the Meikirch model reveals that in many areas more can be done to improve people’s health and to reduce health care costs than is done today. The Meikirch model appears promising for individual and public health in low and high income countries. Emphasizing health instead of disease the Meikirch model reinforces article 12 of the International Covenant on Economic, Social and Cultural Rights of the United Nations – that abandons the WHO definition - and thereby may contribute to its reinterpretation.
Improving quality for maternal care - a case study from Kerala, India
Authors: Vlad Ioana , Paily VP , Sadanandan Rajeev , Cluzeau Françoise , Beena M , Nair Rajasekharan , Newbatt Emma , Ghosh Sujit , Sandeep K , Chalkidou Kalipso 
Published: February 2016

Background: The implementation of maternal health guidelines remains unsatisfactory, even for simple, well established interventions. In settings where most births occur in health facilities, as is the case in Kerala, India, preventing maternal mortality is linked to quality of care improvements. Context: Evidence-informed quality standards (QS), including quality statements and measurable structure and process indicators, are one innovative way of tackling the guideline implementation gap. Having adopted a zero tolerance policy to maternal deaths, the Government of Kerala worked in partnership with the Kerala Federation of Obstetricians & Gynaecologists (KFOG) and NICE International to select the clinical topic, develop and initiate implementation of the first clinical QS for reducing maternal mortality in the state. Description of practice: The NICE QS development framework was adapted to the Kerala context, with local ownership being a key principle. Locally generated evidence identified post-partum haemorrhage as the leading cause of maternal death, and as the key priority for the QS. A multidisciplinary group (including policy-makers, gynaecologists and obstetricians, nurses and administrators) was established. Multi-stakeholder workshops convened by the group ensured that the statements, derived from global and local guidelines, and their corresponding indicators were relevant and acceptable to clinicians and policy-makers in Kerala. Furthermore, it helped identify practical methods for implementing the standards and monitoring outcomes. Lessons learned: An independent evaluation of the project highlighted the equal importance of a strong evidence-base and an inclusive development process. There is no one-size-fits-all process for QS development; a principle-based approach might be a better guide for countries to adapt global evidence to their local context.
Mnemotropic and anxiolytic activity of mexidol and enoxifol
Authors: Трегубова  , Tregubova I. 
Published: February 2016

The article presents the research findings of influence of antioxidant compounds Enoxifol
(10 mg/kg) and Mexidol (100 mg/kg) on behavior, emotional sphere and ability for self-regulation of experimental
animals. The mechanism of Enoxifol and Mexidol action at high nervous functions was established on the
basis of tests allowing to connect behavior reactions with the main neuromediator systems. In the “open field”
test the emotional labality, stress resistance and research activity were evaluated in control rats and rats treated
for three days by antioxidants. The experiments revealed that Enoxifol diminished aggressiveness, step of domination
and degree of neurotic reactions of animals, increased the resistance to emotional load which was accomplished
by the more firm preservation of the memory track then in intact animals. These changes in high nervous
functions were caused by antiadrenergic, choline- and GABA-positive activity of Enoxifol. Mexidol in turn posessed
mnemotropic effect as well, but hasn’t affected the level of stress resistance in experimental rats. Mexidol
modulated acetilecholine, benzodiazepine and GABA receptors in a brain.
Mathematical modeling of immunological parameters for the prediction and diagnosis of chronic non-communicable diseases among health care workers
Authors: Рогалев  , Rogalev K. , Шишова  , Shishova A. , Мартынова  , Martynova N. , Басова  , Basova L. , Ермолина  , Ermolina Tatyana , Родионов  , Rodionov G. 
Published: February 2016

This article presents a mathematical method of interpretation of immunological parameters of
blood. The study used a comprehensive evaluation of the possibility of disease development, not only on the
basis of qualitative data, directly gender-related characteristics and professional activities (occupation, profile,
department, work with the equipment), but also quantitative data - age, work experience, immunological indicators
of the level of immune protection of the subject. The analysis of multidimensional data allowed to identifying
immunological symptoms as predictors of chronic non-communicable diseases. The risk of chronic noncommunicable
diseases among the health care workers is the largest extent dependent on exposure to occupational
factors. The proposed method is the mathematical interpretation of immunological indices of blood, it allowed
to reveal immunological symptoms as predictors of chronic non-communicable diseases. The immunologВЕСТНИК
НОВЫХ МЕДИЦИНСКИХ ТЕХНОЛОГИЙ – 2015 – N 4
Электронный журнал
Библиографическая ссылка:
Т.А. Ермолина, А.В. Шишова, К.К. Рогалев, Н.А. Мартынова, Л.А. Басова, Г.Г. Родионов Математическое модели-
рование иммунологических показателей для прогнозирования и диагностики хронических неинфекционных заболе-
ваний у медицинских работников // Вестник новых медицинских технологий. Электронное издание. 2015. №4. Пуб-
ликация 1-1. URL: http://www.medtsu.tula.ru/VNMT/Bulletin/E2015-4/5221.pdf (дата обращения: 27.11.2015). DOI:
10.12737/16163
ical detection of the symptom of a health worker at the health screening can be considered as a possible predisposition
or the presence of chronic non-communicable diseases and the subsequent development of complex
diagnostic and therapeutic measures. The health assessment can be carried out not at the stage of identifying already
clinically developed chronic non-communicable diseases, and at the initial stage of the disease. This approach
is feasible due to the fact that the initial reversible disorders. Complex timely preventive and therapeutic
measures can prevent the development of chronic non-communicable diseases.
Modern assessment methods of the effectiveness of chewing phases in orthopedic treatment (literature review)
Authors: Васильева  , Vasileva T. , Митин  , Mitin N. , Гришин  , Grishin M. 
Published: February 2016

In this literature review details the diversity of methods for determining the chewing efficiency,
currently existing in the dental practice. Chewing is one of the main functions of the dental system, determine its
condition. Chewing efficiency largely depends on the state of the entire dentition. Therefore, the quality of orthopedic
treatment at different stages of permissible assessed using various methods for determining the efficiency
of chewing. The article discusses in detail current methods of assessing the function of chewing phases of
orthopedic treatment. A brief description of the nature of each method definition chewing efficiency, according
to the classification is presented in the literature. A comparative characteristic of the positive and negative aspects
of the known methods is carried out. The authors assess their labor intensity, sensitivity, availability and
distribution, diversity and quality of the used test material. A special place is the consideration of modern methods,
based on an assessment of the effectiveness of chewing area of occlusal contact with the various techniques
of computerized data analysis. The authors do attempt to explore the possibilities of various systems of
computerized analysis of occlusion for the assessment of chewing efficiency, taking into account the accuracy of
individual features and occlusal relationship. They emphasize efficiency, high precision of the studied method
and the need for further development of this direction in the dental practice.
Immunological aspects of pathogenetic therapy of genital herpes by intravenous laser light of blood
Authors: Зиганшин  , Ziganshin O. , Москвин  , Moskvin S. , Гизингер  , Gizinger O. , Шеметова  , Shemetova M. 
Published: February 2016

Chronic recurrent herpes virus infection of the genitals caused by the herpes virus type 2 is an
inflammatory polyetiological disease, in the pathogenesis of which the reduction of non-specific resistance of the
organism, an imbalance of immune factors plays an important role. Treatment of genital herpes infection should
cover all the links of pathogenesis, including immunological. Clinical and immunological assessment of the effectiveness
of intravenous laser light of blood in the UV spectral range (wavelength 365 nm, the device &#34;Lasmik-
VLOK&#34;) was carried out. This study involved 79 women at the age of 29,9±0,2 years with clinical signs of
chronic recurrent genital herpes.
Etiotropic therapy was conducted with the use of the Aciclovir in a dose of 500 mg once a day for 6
months. The complex therapy included the use of laser ultrasonic irradiation of blood simultaneously with the
application of standard methods of treatment. The results of the study indicate the presence of positive clinical
dynamics and immune-modulating activity of laser ultrasonic spectrum, that allows to recommend this method
in complex therapy of chronic recurrent genital herpes.
Lipid peroxidation and antioxidant system in patients with acute мyocardial infarction and diabetes mellitus type 2
Authors: Загородняя  , Zagorodnyaya T. , Корниенко  , Kornienko E. , Иванов  , Ivanov D. 
Published: February 2016

Problems of the treatment of comorbid patients in routine clinical practice remain highly relevant.
One of the most common combinations – coronary heart disease and diabetes mellitus type 2. In this article,
the authors present their own experience of studying the effects of infusion of the drug &#34;Reamberin&#34; at the
stage of percutaneous coronary intervention on the dynamics of indicators of lipid peroxidation in patients with
myocardial infarction with diabetes mellitus type 2. This study consists of the examination and treatment analysis
of 54 patients, men aged 64,3 ± 6,8 years old with coronary heart disease and clinical manifestations of acute
myocardial infarction and concomitant diabetes mellitus type 2. The percutaneous intervention was made of this
group of patients. To determine the normal values of the studied parameters, the examination of 34 patients with
coronary heart disease without exacerbation (men aged 62,5 ± 4,2 years) with concomitant diabetes mellitus type
2, was carried out. It is found that the development of acute myocardial infarction in patients with diabetes type 2
is accompanied by activation of processes of lipid peroxidation and antioxidant system of blood with a predominance
of lipid peroxidation. It is proved that the use of succinic acid drug &#34;Reamberin&#34; at the stage of percutaneous
coronary intervention in these patients contributes to the decrease in the intensity of free radical processes
and increases the activity of enzymatic antioxidants.