bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia‐inducible factors: coupling glucose metabolism and redox regulation with induction of the breast cancer stem cell phenotype
Authors: Semenza Gregg L 
Published: December 2016

AbstractReduced oxygen availability (hypoxia) leads to increased production of reactive oxygen species (ROS) by the electron transport chain. Here, I review recent work delineating mechanisms by which hypoxia‐inducible factor 1 (HIF‐1) mediates adaptive metabolic responses to hypoxia, including increased flux through the glycolytic pathway and decreased flux through the tricarboxylic acid cycle, in order to decrease mitochondrial ROS production. HIF‐1 also mediates increased flux through the serine synthesis pathway and mitochondrial one‐carbon (folate cycle) metabolism to increase mitochondrial antioxidant production (NADPH and glutathione). Dynamic maintenance of ROS homeostasis is required for induction of the breast cancer stem cell phenotype in response to hypoxia or cytotoxic chemotherapy. Consistently, inhibition of phosphoglycerate dehydrogenase, the first enzyme of the serine synthesis pathway, in breast cancer cells impairs tumor initiation, metastasis, and response to cytotoxic chemotherapy. I discuss how these findings have important implications for understanding the logic of the tumor microenvironment and for improving therapeutic responses in women with breast cancer.
Proteomics reveals the effects of sustained weight loss on the human plasma proteome
Authors: Geyer Philipp E , Wewer Albrechtsen Nicolai J , Tyanova Stefka , Grassl Niklas , Iepsen Eva W , Lundgren Julie , Madsbad Sten , Holst Jens J , Torekov Signe S , Mann Matthias 
Published: December 2016

AbstractSustained weight loss is a preferred intervention in a wide range of metabolic conditions, but the effects on an individual's health state remain ill‐defined. Here, we investigate the plasma proteomes of a cohort of 43 obese individuals that had undergone 8 weeks of 12% body weight loss followed by a year of weight maintenance. Using mass spectrometry‐based plasma proteome profiling, we measured 1,294 plasma proteomes. Longitudinal monitoring of the cohort revealed individual‐specific protein levels with wide‐ranging effects of losing weight on the plasma proteome reflected in 93 significantly affected proteins. The adipocyte‐secreted SERPINF1 and apolipoprotein APOF1 were most significantly regulated with fold changes of −16% and +37%, respectively (P < 10−13), and the entire apolipoprotein family showed characteristic differential regulation. Clinical laboratory parameters are reflected in the plasma proteome, and eight plasma proteins correlated better with insulin resistance than the known marker adiponectin. Nearly all study participants benefited from weight loss regarding a ten‐protein inflammation panel defined from the proteomics data. We conclude that plasma proteome profiling broadly evaluates and monitors intervention in metabolic diseases.
MANAGEMENT OF ENDOCRINE DISEASE: The impact of subclinical hypothyroidism on anthropometric characteristics, lipid, glucose and hormonal profile of PCOS patients: a systematic review and meta-analysis
Authors: Pergialiotis Vasilios , Konstantopoulos Panagiotis , Prodromidou Anastasia , Florou Venetia , Papantoniou Nikolaos , Perrea Despina N 
Published: December 2016

Objective
Subclinical hypothyroidism (SCH) is encountered in 10–25% of women with PCOS. To date, it remains unclear whether this coexistence influences the severity of metabolic and hormonal profile of these patients. The purpose of our systematic review is to investigate this potential relation.

Methods
We systematically searched Medline, Scopus, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases together with reference lists from included studies. All prospective and retrospective observational cohort studies that investigated the impact of subclinical hypothyroidism on hormonal and metabolic parameters of PCOS patients were included. The methodological quality of studies was assessed with the Ottawa–Newcastle criteria. Statistical meta-analysis was performed with the RevMan 5.3 software.

Results
Twelve studies were finally included in the present review, which enrolled 2341 PCOS patients. Among them, 577 had subclinical hypothyroidism, whereas the remaining 2077 were PCOS women with normal thyroid function. The presence of SCH significantly affected HDL (MD –3.92 mg/dL 95% CI: –6.56, –1.29) and triglycerides levels (26.91 mg/dL 95% CI: –3.79, 50.02). HOMA-IR was also affected (MD 0.82 95% CI: 0.15, 1.50). On the other hand, LDL, fasting glucose and 2-h OGTT were not influenced. Similarly, prolactin, FSH, LH, LH/FSH ratio and sex hormone-binding globulin remained unaffected.

Conclusion
Subclinical hypothyroidism does not influence the hormonal profile of women with PCOS. On the other hand, it results in mild metabolic abnormalities, which are not clinically important in a short-term setting.
Cabergoline for Cushing’s disease: a large retrospective multicenter study
Authors: Ferriere A , Cortet C , Chanson P , Delemer B , Caron P , Chabre O , Reznik Y , Bertherat J , Rohmer V , Briet C , Raingeard I , Castinetti F , Beckers A , Vroonen L , Maiter D , Cephise-Velayoudom F L , Nunes M L , Haissaguerre M , Tabarin A 
Published: December 2016

ObjectiveThe efficacy of cabergoline in Cushing’s disease (CD) is controversial. The aim of this study was to assess the efficacy and tolerability of cabergoline in a large contemporary cohort of patients with CD.DesignWe conducted a retrospective multicenter study from thirteen French and Belgian university hospitals.MethodsSixty-two patients with CD received cabergoline monotherapy or add-on therapy. Symptom score, biological markers of hypercortisolism and adverse effects were recorded.ResultsTwenty-one (40%) of 53 patients who received cabergoline monotherapy had normal urinary free cortisol (UFC) values within 12 months (complete responders), and five of these patients developed corticotropic insufficiency. The fall in UFC was associated with significant reductions in midnight cortisol and plasma ACTH, and with clinical improvement. Compared to other patients, complete responders had similar median baseline UFC (2.0 vs 2.5xULN) and plasma prolactin concentrations but received lower doses of cabergoline (1.5 vs 3.5 mg/week,P < 0.05). During long-term treatment (>12 months), cabergoline was withdrawn in 28% of complete responders because of treatment escape or intolerance. Overall, sustained control of hypercortisolism was obtained in 23% of patients for 32.5 months (19–105). Nine patients on steroidogenesis inhibitors received cabergoline add-on therapy for 19 months (1–240). Hypercortisolism was controlled in 56% of these patients during the first year of treatment with cabergoline at 1.0 mg/week (0.5–3.5).ConclusionsAbout 20–25% of CD patients are good responders to cabergoline therapy allowing long-term control of hypercortisolism at relatively low dosages and with acceptable tolerability. No single parameter, including the baseline UFC and prolactin levels, predicted the response to cabergoline.
General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization
Authors: Tate Jennifer J , Buford David , Rai Rajendra , Cooper Terrance G 
Published: December 2016

Abstract
Nitrogen catabolite repression (NCR), the ability of Saccharomyces cerevisiae to use good nitrogen sources in preference to poor ones, derives from nitrogen-responsive regulation of the GATA family transcription activators Gln3 and Gat1. In nitrogen-replete conditions, the GATA factors are cytoplasmic and NCR-sensitive transcription minimal. When only poor nitrogen sources are available, Gln3 is nuclear, dramatically increasing GATA factor-mediated transcription. This regulation was originally attributed to mechanistic Tor protein kinase complex 1 (mTorC1)-mediated control of Gln3. However, we recently showed that two regulatory systems act cumulatively to maintain cytoplasmic Gln3 sequestration, only one of which is mTorC1. Present experiments demonstrate that the other previously elusive component is uncharged transfer RNA-activated, Gcn2 protein kinase-mediated general amino acid control (GAAC). Gcn2 and Gcn4 are required for NCR-sensitive nuclear Gln3-Myc13 localization, and from epistasis experiments Gcn2 appears to function upstream of Ure2. Bmh1/2 are also required for nuclear Gln3-Myc13 localization and appear to function downstream of Ure2. Overall, Gln3 phosphorylation levels decrease upon loss of Gcn2, Gcn4, or Bmh1/2. Our results add a new dimension to nitrogen-responsive GATA-factor regulation and demonstrate the cumulative participation of the mTorC1 and GAAC pathways, which respond oppositely to nitrogen availability, in the nitrogen-responsive control of catabolic gene expression in yeast.
Spiraling Complexity: A Test of the Snowball Effect in a Computational Model of RNA Folding
Authors: Kalirad Ata , Azevedo Ricardo B R 
Published: December 2016

AbstractThe snowball hypothesis suggests that the number of genetic incompatibilities between two populations will accumulate faster than linearly as they diverge...Genetic incompatibilities can emerge as a byproduct of genetic divergence. According to Dobzhansky and Muller, an allele that fixes in one population may be incompatible with an allele at a different locus in another population when the two alleles are brought together in hybrids. Orr showed that the number of Dobzhansky-Muller incompatibilities (DMIs) should accumulate faster than linearly—i.e., snowball—as two lineages diverge. Several studies have attempted to test the snowball effect using data from natural populations. One limitation of these studies is that they have focused on predictions of the Orr model, but not on its underlying assumptions. Here, we use a computational model of RNA folding to test both predictions and assumptions of the Orr model. Two populations are allowed to evolve in allopatry on a holey fitness landscape. We find that the number of inviable introgressions (an indicator for the number of DMIs) snowballs, but does so more slowly than expected. We show that this pattern is explained, in part, by the fact that DMIs can disappear after they have arisen, contrary to the assumptions of the Orr model. This occurs because DMIs become progressively more complex (i.e., involve alleles at more loci) as a result of later substitutions. We also find that most DMIs involve &gt;2 loci, i.e., they are complex. Reproductive isolation does not snowball because DMIs do not act independently of each other. We conclude that the RNA model supports the central prediction of the Orr model that the number of DMIs snowballs, but challenges other predictions, as well as some of its underlying assumptions.
Evidence for Amino Acid Snorkeling from a High-Resolution,In VivoAnalysis of Fis1 Tail-Anchor Insertion at the Mitochondrial Outer Membrane
Authors: Keskin Abdurrahman , Akdoğan Emel , Dunn Cory D 
Published: December 2016

AbstractProteins localized to mitochondria by a carboxyl-terminal tail anchor (TA) play roles in apoptosis, mitochondrial dynamics, and mitochondrial protein import. To reveal characteristics of TAs that may be important for mitochondrial targeting, we focused our attention upon the TA of the Saccharomyces cerevisiae Fis1 protein. Specifically, we generated a library of Fis1p TA variants fused to the Gal4 transcription factor, then, using next-generation sequencing, revealed which Fis1p TA mutations inhibited membrane insertion and allowed Gal4p activity in the nucleus. Prompted by our global analysis, we subsequently analyzed the ability of individual Fis1p TA mutants to localize to mitochondria. Our findings suggest that the membrane-associated domain of the Fis1p TA may be bipartite in nature, and we encountered evidence that the positively charged patch at the carboxyl terminus of Fis1p is required for both membrane insertion and organelle specificity. Furthermore, lengthening or shortening of the Fis1p TA by up to three amino acids did not inhibit mitochondrial targeting, arguing against a model in which TA length directs insertion of TAs to distinct organelles. Most importantly, positively charged residues were more acceptable at several positions within the membrane-associated domain of the Fis1p TA than negatively charged residues. These findings, emerging from the first high-resolution analysis of an organelle targeting sequence by deep mutational scanning, provide strong, in vivo evidence that lysine and arginine can “snorkel,” or become stably incorporated within a lipid bilayer by placing terminal charges of their side chains at the membrane interface.
Feeding-Related Traits Are Affected by Dosage of theforagingGene inDrosophila melanogaster
Authors: Allen Aaron M , Anreiter Ina , Neville Megan C , Sokolowski Marla B 
Published: December 2016

AbstractNutrient acquisition and energy storage are critical parts of achieving metabolic homeostasis. The foraging gene in Drosophila melanogaster has previously been implicated in multiple feeding-related and metabolic traits. Before foraging’s functions can be further dissected, we need a precise genetic null mutant to definitively map its amorphic phenotypes. We used homologous recombination to precisely delete foraging, generating the for0 null allele, and used recombineering to reintegrate a full copy of the gene, generating the {forBAC} rescue allele. We show that a total loss of foraging expression in larvae results in reduced larval path length and food intake behavior, while conversely showing an increase in triglyceride levels. Furthermore, varying foraging gene dosage demonstrates a linear dose-response on these phenotypes in relation to foraging gene expression levels. These experiments have unequivocally proven a causal, dose-dependent relationship between the foraging gene and its pleiotropic influence on these feeding-related traits. Our analysis of foraging’s transcription start sites, termination sites, and splicing patterns using rapid amplification of cDNA ends (RACE) and full-length cDNA sequencing, revealed four independent promoters, pr1–4, that produce 21 transcripts with nine distinct open reading frames (ORFs). The use of alternative promoters and alternative splicing at the foraging locus creates diversity and flexibility in the regulation of gene expression, and ultimately function. Future studies will exploit these genetic tools to precisely dissect the isoform- and tissue-specific requirements of foraging’s functions and shed light on the genetic control of feeding-related traits involved in energy homeostasis.
Responsible Innovation in Children’s Surgical Care
Authors:   SECTION ON SURGERY,   COMMITTEE ON BIOETHICS,   AMERICAN PEDIATRIC SURGICAL ASSOCIATION NEW TECHNOLOGY COMMITTEE, Caty Michael G. , Besner Gail Ellen , Davidoff Andrew , Fallat Mary , Heiss Kurt F. , Meyers Rebecka L. , Moss R. Lawrence , Katz Aviva L. , Laventhal Naomi Tricot , Macauley Robert C. , Moon Margaret Rusha , Okun Alexander L. , Opel Douglas J. , Statter Mindy B. , Breuer Christopher K. , Skarsgard Erik D. , Barnett Sean J. , Dutta Sanjeev , Fairbanks Timothy J. , Jarboe Marcus , Scholz Stefan , Teich Steven , Woo Russell K. , Wall James K. 
Published: December 2016

This Policy Statement was reaffirmed September 12, 2023.
Advances in medical care may occur when a change in practice incorporates a new treatment or methodology. In surgery, this may involve the translation of a completely novel concept into a new procedure or device or the adaptation of existing treatment approaches or technology to a new clinical application. Regardless of the specifics, innovation should have, as its primary goal, the enhancement of care leading to improved outcomes from the patient’s perspective. This policy statement examines innovation as it pertains to surgical care, focusing on some of the definitions that help differentiate applied innovation or innovative therapy from research. The ethical challenges and the potential for conflict of interest for surgeons or institutions seeking to offer innovative surgical therapy are examined. The importance of engaging patients and families as “innovation partners” to ensure complete transparency of expectations from the patient’s and provider’s perspectives is also examined, with specific emphasis on cultural competence and mutually respectful approaches. A framework for identifying, evaluating, and safely implementing innovative surgical therapy in children is provided.
A postmodern mandala? Moving beyond methodological nationalism
Authors: Sutherland Claire 
Published: December 2016

The colonial translation of the “nation-state logic” to Southeast Asia is commonly understood to have superseded what O.W. Wolters called the pre-colonial mandala model, in which power was exerted by a sort of central “sun king” whose gravitational pull weakened with distance and was overlapped by other spheres of power in a complex system of tributary relationships. The historian David Biggs has argued that, in accepting the undeniable importance of national sovereignty in contemporary political analyses of Southeast Asia, there has been too definitive a break with pre-existing understandings of power relations, which may prove useful to explaining the particularities of politics today. In political science, the translation of nationalism and sovereignty to Southeast Asia is reflected in an entrenched “methodological nationalism,” whereby the nation-state is frequently taken for granted as the central unit of analysis. Paying attention to the “margins” of society still implicitly assumes a national centre, for example. Historians of Vietnam, including Keith Taylor and Li Tana, have made significant advances in loosening the “stranglehold” of nationalist historiography. Anthropologists and geographers of cosmopolitanism and migration have also long questioned the analytical usefulness of bordered nation-states. Building on these insights, the article calls for a paradigm shift in political enquiry and playfully proposes the “post-modern mandala” as an alternative to methodological nationalism applied to Southeast Asia.
ENERGY SAVING DURING OPERATION OF EQUIPMENT WITH NON-CONTROLLED ELECTRIC DRIVE IN LOCOMOTIVE DEPOT
Authors: Dubynets L. V. , Marenych O. L. , Baliichuk O. Yu. , Kortohus A. S. 
Published: December 2016

Purpose. To conduct research of electric motors in order to obtain the results that will assess the degree of energy saving due to electric loss reduction in the equipment with non-controlled electric drive. Methodology. The paper proposes an engineering method for determination of active power losses in the motors of the equipment with non-controlled electric drive in locomotive depot during load changes on the motor shaft. It is necessary to analyse the reduction of active power losses in the motor and the power supply network when an under-loaded motor is replaced with a motor having less power. Findings. After the calculations performed by the authors, it was found that for electric motors, in case of reducing the load factor from to active loss reduction after the motor replacement for the less powerful one ranges from 0.58 kW to 2.865 kW. Also, the calculations were carried out on the example of electric motors with a lower synchronous speed, the effect of under-loaded motor replacement increases in terms of active power loss reduction. The greatest effect is achieved when the load factor is . Originality. For the first time the paper outlines the issues of energy saving efficiency for the equipment with non-controlled electric drive in locomotive depot by replacing the under-loaded motors with the less powerful ones. As long as there is a significant amount of the considered electric drives, it may cause severe losses, taking into account the peculiarities of their operation. Practical value. The obtained research results allow us to solve the problem of replacement of under-loaded motors in locomotive depot equipment with the motors having less power as efficiently as possible in terms of reducing electric losses. For instance 90-kW motor of a washing machine can be replaced with 75-kW motor when the load factor is , this can significantly reduce the performance losses. This method can be applied not only in locomotive depot but also for all equipment with non-controlled electric drives that operates in under-load mode.
Collective Co-Production in Russian Schools
Authors: Suslova Svetlana 
Published: December 2016

The growing demand for quality education services, as well as financial constraints faced by educational institutions produce the need for active involvement of parents and other representatives of local communities in the educational process so as to provide schools with additional resources. As a form of such involvement, non-profit organizations (NPOs) can be established to support educational institutions. In this paper, we assess the level of collective co-production in Russian school education and look for orrelations between institutional characteristics of schools and their cooperation with NPOs. The data for research was obtained from the Unified State Register of Legal Entities (through the SPARK System), websites of municipal departments of education, and publicly available sources of information about activities of NPOs supporting schools. We reveal considerable cross-regional differences in the development of collective co-production in school education. The process is more active in provincial towns than in megalopolises: the proportion of schools supported by specifically founded NPOs is higher in many regional centers than in the capital cities. At the same time, a lot of regions have no such NPOs at all. As it turns out, NPOs are more likely to be created to support schools with a special status (gymnasiums, lyceums and specialized schools), where the parental demand for quality education services is higher. Meanwhile, we found no correlation between autonomous status of educational institutions and their participation in collective co-production. Thus, the increased degree of independence did not induce cooperation with NPOs for the purpose of raising extra-budgetary funds in this case.
Estudo de espólio cerâmico proveniente do interior de uma habitação almóada da alcáçova de Alcácer do Sal (Portugal)
Authors: Caetano Leitão Marta Isabel 
Published: December 2016

Dá-se a conhecer um conjunto de cerâmicas, datáveis entre a segunda metade do século XII e primeira metade do XIII, exumadas no interior de uma habitação, entre os anos de 1993-1997, no decorrer de intervenções arqueológicas realizadas no Convento de Nossa Senhora de Aracoeli (anterior alcáçova muçulmana) em Alcácer do Sal e que permitiram datar aquele espaço do Período Almóada.