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https://www.readbyqxmd.com/read/28445746/crosstalk-and-the-dynamical-modularity-of%C3%A2-feed-forward-loops-in-transcriptional-regulatory-networks
#1
Michael A Rowland, Ahmed Abdelzaher, Preetam Ghosh, Michael L Mayo
Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (≈20% for one crosstalk interaction) and remain dynamically modular...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445611/equivalence-of-complex-drug-products-advances-in-and-challenges-for-current-regulatory-frameworks
#2
Leonie Hussaarts, Stefan Mühlebach, Vinod P Shah, Scott McNeil, Gerrit Borchard, Beat Flühmann, Vera Weinstein, Sesha Neervannan, Elwyn Griffiths, Wenlei Jiang, Elena Wolff-Holz, Daan J A Crommelin, Jon S B de Vlieger
Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U...
April 26, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28445502/role-of-kif15-and-its-novel-mitotic-partner-kbp-in-k-fiber-dynamics-and-chromosome-alignment
#3
Nathalie Brouwers, Nuria Mallol Martinez, Isabelle Vernos
Faithful segregation of the genetic material during the cell cycle is key for the continuation of life. Central to this process is the assembly of a bipolar spindle that aligns the chromosomes and segregates them to the two daughter cells. Spindle bipolarity is strongly dependent on the activity of the homotetrameric kinesin Eg5. However, another kinesin, Kif15, also provides forces needed to separate the spindle poles during prometaphase and to maintain spindle bipolarity at metaphase. Here we identify KBP as a specific interaction partner of Kif15 in mitosis...
2017: PloS One
https://www.readbyqxmd.com/read/28445471/a-randomized-trial-comparing-concise-and-standard-consent-forms-in-the-start-trial
#4
Christine Grady, Giota Touloumi, A Sarah Walker, Mary Smolskis, Shweta Sharma, Abdel G Babiker, Nikos Pantazis, Jorge Tavel, Eric Florence, Adriana Sanchez, Fleur Hudson, Antonios Papadopoulos, Ezekiel Emanuel, Megan Clewett, David Munroe, Eileen Denning
BACKGROUND: Improving the effectiveness and efficiency of research informed consent is a high priority. Some express concern about longer, more complex, written consent forms creating barriers to participant understanding. A recent meta-analysis concluded that randomized comparisons were needed. METHODS: We conducted a cluster-randomized non-inferiority comparison of a standard versus concise consent form within a multinational trial studying the timing of starting antiretroviral therapy in HIV+ adults (START)...
2017: PloS One
https://www.readbyqxmd.com/read/28445088/predicting-the-need-for-third-line-antiretroviral-therapy-by-identifying-patients-at-high-risk-for-failing-second-line-antiretroviral-therapy-in-south-africa
#5
Dorina Onoya, Cornelius Nattey, Eric Budgell, Liudmyla van den Berg, Mhairi Maskew, Denise Evans, Kamban Hirasen, Lawrence C Long, Matthew P Fox
Although third-line antiretroviral therapy (ART) is available in South Africa's public sector, its cost is substantially higher than first and second line. Identifying risk factors for failure on second-line treatment remains crucial to reduce the need for third-line drugs. We conducted a case-control study including 194 adult patients (≥18 years; 70 cases and 124 controls) who initiated second-line ART in Johannesburg, South Africa. Unconditional logistic regression was used to assess predictors of virologic failure (defined as 2 consecutive viral load measures ≥1000 copies/mL, ≥3 months after switching to second line)...
April 26, 2017: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/28445008/prevalence-of-complement-mediated-cell-lysis-like-gene-sicg-in-streptococcus-dysgalactiae-subsp-equisimilis-isolates-from-japan-2014-2016
#6
Takashi Takahashi, Tomohiro Fujita, Akiyoshi Shibayama, Yuzo Tsuyuki, Haruno Yoshida
BACKGROUND: Streptococcus dysgalactiae subsp. equisimilis (SDSE; a β-hemolytic streptococcus of human or animal origin) infections are emerging worldwide. We evaluated the clonal distribution of complement-mediated cell lysis-like gene (sicG) among SDSE isolates from three central prefectures of Japan. METHODS: Group G/C β-hemolytic streptococci were collected from three institutions from April 2014 to March 2016. Fifty-five strains (52 from humans and three from animals) were identified as SDSE on the basis of 16S rRNA sequencing data...
July 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28444285/preeclampsia-screening-evidence-report-and-systematic-review-for-the-us-preventive-services-task-force
#7
Jillian T Henderson, Jamie H Thompson, Brittany U Burda, Amy Cantor
Importance: Preeclampsia is a complex disease of pregnancy with sometimes serious effects on maternal and infant morbidity and mortality. It is defined by hypertension after 20 weeks' gestation and proteinuria or other evidence of multisystem involvement. Objective: To systematically review the benefits and harms of preeclampsia screening and risk assessment for the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases from 1990 through September 1, 2015...
April 25, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28444218/current-dilemmas-in-defining-the-boundaries-of-disease
#8
Jenny Doust, Mary Jean Walker, Wendy A Rogers
Boorse's biostatistical theory states that diseases should be defined in ways that reflect disturbances of biological function and that are objective and value free. We use three examples from contemporary medicine that demonstrate the complex issues that arise when defining the boundaries of disease: polycystic ovary syndrome, chronic kidney disease, and myocardial infarction. We argue that the biostatistical theory fails to provide sufficient guidance on where the boundaries of disease should be drawn, contains ambiguities relating to choice of reference class, and is out of step with medical processes for identifying disease boundaries...
April 21, 2017: Journal of Medicine and Philosophy
https://www.readbyqxmd.com/read/28444192/from-reproducibility-to-translation-in-neurodegenerative-disease
#9
Caroline J Zeiss
Despite tremendous investment and preclinical success in neurodegenerative disease, effective disease-altering treatments for patients have remained elusive. One highly cited reason for this discrepancy is flawed animal study design and reporting. If this can be broadly remedied, reproducibility of preclinical studies will improve. However, without concurrent efforts to improve generalizability, these improvements may not translate effectively from animal experiments to more complex human neurodegenerative diseases...
April 21, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28444032/thoughts-on-the-development-of-active-regional-public-health-systems
#10
Ademar Arthur Chioro Dos Reis, Ana Paula Menezes Sóter, Lumena Almeida Castro Furtado, Silvana Souza da Silva Pereira
Decentralization and regionalization are strategic themes for reforms in the health system. This paper analyzes the complex process of health regionalization being developed in Brazil. This paper identifies that the normative framework from the Brazilian National Health System, SUS has made advances with respect to its institutionalization and overcoming the initial centrality involved in municipalization. This has strengthened the development of regionalization and the intergovernmental agreement on health but the evidence points to the need to promote a revision...
April 2017: Ciência & Saúde Coletiva
https://www.readbyqxmd.com/read/28444019/non-surgical-treatment-of-transverse-deficiency-in-adults-using-microimplant-assisted-rapid-palatal-expansion-marpe
#11
Daniel Paludo Brunetto, Eduardo Franzzotti Sant'Anna, Andre Wilson Machado, Won Moon
INTRODUCTION: Maxillary transverse deficiency is a highly prevalent malocclusion present in all age groups, from primary to permanent dentition. If not treated on time, it can aggravate and evolve to a more complex malocclusion, hindering facial growth and development. Aside from the occlusal consequences, the deficiency can bring about serious respiratory problems as well, due to the consequent nasal constriction usually associated. In growing patients, this condition can be easily handled with a conventional rapid palatal expansion...
February 2017: Dental Press Journal of Orthodontics
https://www.readbyqxmd.com/read/28444016/frictionless-segmented-mechanics-for-controlled-space-closure
#12
Ildeu Andrade
Extraction spaces may be needed to achieve specific orthodontic goals of positioning the dentition in harmony with the craniofacial complex. However, the fundamental reality that determines the occlusion final position is the control exerted by the orthodontist while closing the extraction spaces. A specific treatment objective may require the posterior teeth to remain in a constant position anteroposteriorly as well as vertically, while the anterior teeth occupy the entire extraction site. Another treatment objective may require the opposite, or any number of intentional alternatives of extraction site closure...
February 2017: Dental Press Journal of Orthodontics
https://www.readbyqxmd.com/read/28443330/mechanisms-by-which-salt-concentration-moderates-the-dynamics-of-human-serum-transferrin
#13
Haleh Abdizadeh, Ali Rana Atilgan, Canan Atilgan
The dynamical and thermodynamic behavior of human transferrin (hTf) protein in saline aqueous solution of various concentrations is studied. hTf is an essential transport protein circulating iron in the blood and delivering it to tissues. It displays highly pH dependent cooperativity between the two lobes each carrying an iron, and forms a tight complex with the receptor during endocytosis, eventually recycled to the serum after iron release. Molecular dynamics simulations are used to investigate the effects of the amount of salt on protein conformation and dynamics to analyze the structure-function relationship in free hTf at serum pH...
April 26, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28443274/the-guatemala-penn-partners-an-innovative-inter-institutional-model-for-scientific-capacity-building-healthcare-education-and-public-health
#14
Maria Alejandra Paniagua-Avila, Elizabeth Messenger, Caroline A Nelson, Erwin Calgua, Frances K Barg, Kent W Bream, Charlene Compher, Anthony J Dean, Sergio Martinez-Siekavizza, Victor Puac-Polanco, Therese S Richmond, Rudolf R Roth, Charles C Branas
Population health outcomes are directly related to robust public health programs, access to basic health services, and a well-trained health-care workforce. Effective health services need to systematically identify solutions, scientifically test these solutions, and share generated knowledge. The World Health Organization (WHO)'s Global Healthcare Workforce Alliance states that the capacity to perform research is an essential factor for well-functioning public health systems. Low- and middle-income countries have greater health-care worker shortages and lower research capacity than higher-income countries...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28443269/epidemiology-and-risk-assessment-of-pediatric-venous-thromboembolism
#15
REVIEW
Arash Mahajerin, Stacy E Croteau
The incidence of diagnosed venous thromboembolism (VTE) has been increasing concurrent with advances in technology and medical care that enhance our ability to treat pediatric patients with critical illness or complex multiorgan system dysfunction. Although the overall incidence of VTE is estimated at 0.07-0.49 per 10,000 children, higher rates are observed in specific populations including hospitalized children, those with central venous catheters (CVCs) or patients convalescing from a major surgery. While the absolute number of pediatric VTE events may seem trivial compared to adults, the increasing incidence, associated with increased mortality and morbidity, the availability of novel therapies, and the impact on the cost of care have made investigation of VTE risk factors and prevention strategies a high priority...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28443088/utilizing-anaerobic-fungi-for-two-stage-sugar-extraction-and-biofuel-production-from-lignocellulosic-biomass
#16
Abhaya Ranganathan, Olivia P Smith, Noha H Youssef, Christopher G Struchtemeyer, Hasan K Atiyeh, Mostafa S Elshahed
Lignocellulosic biomass is a vast and underutilized resource for the production of sugars and biofuels. However, the structural complexity of lignocellulosic biomass and the need for multiple pretreatment and enzymatic steps for sugar release renders this process economically challenging. Here, we report a novel approach for direct, single container, exogenous enzyme-free conversion of lignocellulosic biomass to sugars and biofuels using the anaerobic fungal isolate strain C1A. This approach utilizes simple physiological manipulations for timely inhibition and uncoupling of saccharolytic and fermentative capabilities of strain C1A, leading to the accumulation of sugar monomers (glucose and xylose) in the culture medium...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28443051/social-behavior-of-pet-dogs-is-associated-with-peripheral-oxtr-methylation
#17
Giulia Cimarelli, Zsófia Virányi, Borbála Turcsán, Zsolt Rónai, Mária Sasvári-Székely, Zsófia Bánlaki
Oxytocin is a key modulator of emotional processing and social cognitive function. In line with this, polymorphisms of genes involved in oxytocin signaling, like the oxytocin receptor (OXTR) gene, are known to influence social behavior in various species. However, to date, no study has investigated environmental factors possibly influencing the epigenetic variation of the OXTR gene and its behavioral effects in dogs. Pet dogs form individualized and strong relationships with their owners who are central figures in the social environment of their dogs and therefore might influence the methylation levels of their OXTR gene...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28442998/glial-cell-line-derived-neurotrophic-factor-gene-delivery-in-parkinson-s-disease-a-delicate-balance-between-neuroprotection-trophic-effects-and-unwanted-compensatory-mechanisms
#18
REVIEW
Liliane Tenenbaum, Marie Humbert-Claude
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a receptor complex consisting of a member of the GDNF family receptor (GFR)-α and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal dopaminergic neurons and reduce motor symptoms when applied terminally in toxin-induced Parkinson's disease (PD) models. However, clinical trials based on intraputaminal GDNF protein administration or recombinant adeno-associated virus (rAAV)-mediated NRTN gene delivery have been disappointing...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28442935/new-developments-in-the-treatment-of-hypoactive-sexual-desire-disorder-a-focus-on-flibanserin
#19
REVIEW
Christopher J Jayne, Michael J Heard, Sarah Zubair, Dustie L Johnson
The objective of the authors is to highlight the historical complexities for the diagnosis and treatment of hypoactive sexual desire disorder (HSDD) with a focus on Flibanserin. A systematic review of the medical literature published in PubMed using the search terms HSDD and Flibanserin was conducted. Each author reviewed the results of the systematic review for articles to include in this study. HSDD is defined as a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity causing marked distress or interpersonal difficulty that is not better accounted for by another diagnosis...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28442898/medication-regimen-complexity-in-ambulatory-older-adults-with-heart-failure
#20
Michael R Cobretti, Robert L Page, Sunny A Linnebur, Kimberly M Deininger, Amrut V Ambardekar, JoAnn Lindenfeld, Christina L Aquilante
PURPOSE: Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population. We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI) tool in "young-old" (60-74 years) versus "old-old" (75-89 years) patients with heart failure. We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM) versus nonischemic cardiomyopathy (NISCM). PATIENTS AND METHODS: Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60-89 years with heart failure...
2017: Clinical Interventions in Aging
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