bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Roles of the Hemagglutinin Segment-Specific Noncoding Nucleotides in the Extended Duplex Region of the Influenza A Virus RNA Promoter
Authors: Wang Jingfeng , Li Jinghua , Zhao Lili , Cao Mengmeng , Deng Tao 
Published: October 2016

ABSTRACT

We recently reported that the segment-specific noncoding regions (NCRs) of the hemagglutinin (HA) and neuraminidase (NA) segments are subtype specific, varying significantly in sequence and length at both the 3′ and 5′ ends. Interestingly, we found that nucleotides CC at positions 13 and 14 at the 3′ end and GUG at positions 14 to 16 at the 5′ end (termed 14′ and 16′ to distinguish them from 3′ positions) are absolutely conserved among all HA subtype-specific NCRs. These HA segment-specific NCR nucleotides are located in the extended duplex region of the viral RNA promoter. In order to understand the significance of these highly conserved HA segment-specific NCR nucleotides in the virus life cycle, we performed extensive mutagenesis on the HA segment-specific NCR nucleotides and studied their functional significance in regulating influenza A virus replication in the context of the HA segment with both RNP reconstitution and virus infection systems. We found that the base pairing of the 3′-end 13 position with the 5′-end 14′ position (
3′
13-
5′
14′) position is critical for RNA promoter activity while the identity of the base pair is critical in determining HA segment packaging. Moreover, the identity of the residue at the 3′-end 14 position is functionally more important in regulating virus genome packaging than in regulating viral RNA synthesis. Taken together, these results demonstrated that the HA segment-specific NCR nucleotides in the extended duplex region of the promoter not only form part of the promoter but also play a key role in controlling virus selective genome packaging.

IMPORTANCE
The segment-specific complementary nucleotides (13 to 15 in the 3′ end and 14′ to 16′ in the 5′ end) in the extended duplex region of the influenza virus RNA promoter vary significantly among different segments and have rarely been studied. Here, we performed mutagenesis analysis of the highly conserved HA segment-specific nucleotides in the extended duplex region and examined their effects on virus replication in the context of the influenza A/WSN/33 (WSN) virus infection. We found that these HA segment-specific nucleotides not only act as a part of the RNA promoter but also play a critical role in HA segment packaging. Therefore, we showed experimentally, for the first time, the requirement of the nucleotides in the extended duplex region for the RNA promoter and also identified specific noncoding residues in regulating HA segment packaging. This work has implications for the development of attenuated vaccine strains and for elucidation the mechanisms of the virus genome packaging.
Evolution of
Mycobacterium tuberculosis
: New Insights into Pathogenicity and Drug Resistance
Authors: Boritsch Eva C. , Brosch Roland 
Published: October 2016

ABSTRACT

The tuberculosis agent
Mycobacterium tuberculosis
has undergone a long and selective evolution toward human infection and represents one of the most widely spread pathogens due to its efficient aerosol-mediated human-to-human transmission. With the availability of more and more genome sequences, the evolutionary trajectory of this obligate pathogen becomes visible, which provides us with new insights into the molecular events governing evolution of the bacterium and its ability to accumulate drug-resistance mutations. In this review, we summarize recent developments in mycobacterial research related to this matter that are important for a better understanding of the current situation and future trends and developments in the global epidemiology of tuberculosis, as well as for possible public health intervention possibilities.
Lower limb immobilisation and venous thromboembolism risk: combined case–control studies
Authors: Braithwaite Irene , Healy Bridget , Cameron Laird , Weatherall Mark , Beasley Richard 
Published: October 2016

ABSTRACTBackgroundEvidence from randomised controlled trials shows that low-molecular-weight heparin is effective in reducing the risk of venous thromboembolism (VTE) in the clinical setting of temporary lower limb immobilisation. Despite this, international guidelines are non-committal in advocating the use of anticoagulation in this clinical scenario. We determined the risk of VTE associated with lower limb immobilisation and the proportion of VTE events associated with lower limb immobilisation by undertaking a secondary analysis of two case–control studies that had used a similar methodology.MethodsWe undertook logistic regression analysis to investigate the association of risk factors with VTE with the OR and 95% CIs for association between lower limb immobilisation and VTE the primary outcome variable. The proportion of VTE patients with lower limb immobilisation was also calculated.ResultsCases comprised 396 patients aged 18–65 years with radiologically confirmed deep vein thrombosis or pulmonary embolism attending outpatient VTE clinics. Controls, also aged 18–65 years, comprised 197 inpatients in the coronary care unit and 200 outpatients treated for upper limb injuries in the fracture clinic. The OR for association between VTE and lower limb immobilisation was 73.1 (95% CI 10.1 to 530, p&lt;0.001). In 62/396 (16%) cases, patients had undergone lower limb immobilisation within four weeks of their presentation with VTE, representing the most common potentially preventable cause of VTE in this sample.ConclusionsLower limb immobilisation is associated with a markedly increased risk of VTE and represents the most common potentially preventable cause in the 18–65-year age group, being present in one in seven cases treated for VTE. Consideration should be given to pharmacological prophylaxis in patients with lower limb immobilisation to reduce the substantial burden of preventable VTE.
Analysis of Policy-Based Systems with AGILE Policies Using Petri Nets
Authors: Pelc Mariusz 
Published: October 2016

Autonomic and self-* systems of all kinds are expected to operate in a stable and predictable way. This in a natural way implies the need for pre-deployment design-time verification of the decision making logic, meant by a process of proving that the logic deployed into the autonomic service/software component meets all requirements and will not lead to any unpredicted or unwanted behavior. There is actually no simple way that can be used for verification of the decision making logic used self-* and autonomic systems as only methods that use some kind of formalism can in an objective way verify the logic correctness. There is one problem, however, with this kind of approach — the formalism may vary depending on the way the decision making logic is expressed (for example, it may be in the form of a policy). In this paper, an approach to verification of policy decision making logic is based on its transformation into the corresponding Petri net using the proposed methodology. Consequently, the resulting Petri net can then be verified using Petri nets formalism and these verification results can be used to assess policy correctness. Two policies were used to illustrate the approach: ACSPolicy controlling the basic operation of an Air Conditioning System (ACS) in a car and ACSFullPolicy being its more sophisticated version allowing the controlled ACS to work in three pre-defined modes. The second policy shows how easily the proposed methodology scales up allowing the analysis policies of any complexity level.
Effect of sodium nitrite on local control of contracting skeletal muscle microvascular oxygen pressure in healthy rats
Authors: Colburn Trenton D. , Ferguson Scott K. , Holdsworth Clark T. , Craig Jesse C. , Musch Timothy I. , Poole David C. 
Published: October 2016

Exercise intolerance characteristic of diseases such as chronic heart failure (CHF) and diabetes is associated with reduced nitric oxide (NO) bioavailability from nitric oxide synthase (NOS), resulting in an impaired microvascular O2 driving pressure (Po2 mv; O2 delivery/O2 utilization) and metabolic control. Infusions of the potent NO donor sodium nitroprusside augment NO bioavailability yet decrease mean arterial pressure (MAP) thereby reducing its potential efficacy for patient populations. To eliminate or reduce hypotensive sequelae, [Formula: see text] was superfused onto the spinotrapezius muscle. It was hypothesized that local [Formula: see text] administration would elevate resting Po2 mv and slow Po2 mv kinetics [increased time constant (τ) and mean response time (MRT)] following the onset of muscle contractions without decreasing MAP. In 12 anesthetized male Sprague-Dawley rats, Po2 mv of the circulation-intact spinotrapezius muscle was measured by phosphorescence quenching during 180 s of electrically induced twitch contractions (1 Hz) before and after superfusion of sodium nitrite (NaNO2 30 mM). [Formula: see text] superfusion elevated resting Po2 mv (control: 28.4 ± 1.1 vs. [Formula: see text]: 31.6 ± 1.2 mmHg; P ≤ 0.05), τ (control: 12.3 ± 1.2 vs. [Formula: see text]: 19.7 ± 2.2 s; P ≤ 0.05), and MRT (control: 19.3 ± 1.9 vs. [Formula: see text]: 25.6 ± 3.3 s; P ≤ 0.05). Importantly, these effects occurred in the absence of any reduction in MAP (103 ± 4 vs. 105 ± 4 mmHg, pre- and postsuperfusion respectively; P > 0.05). These results indicate that [Formula: see text] supplementation delivered to the muscle directly through [Formula: see text] superfusion enhances the blood-myocyte oxygen driving pressure without compromising MAP at rest and following the onset of muscle contraction. This strategy has substantial clinical utility for a range of ischemic conditions. NEW & NOTEWORTHY Ischemic conditions as diverse as chronic heart failure (CHF) and frostbite inflict tissue damage via inadequate O2 delivery. Herein we demonstrate that direct application of sodium nitrite enhances the O2 supply-O2 demand relationship, raising microvascular O2 pressure in healthy skeletal muscle. This therapeutic action of nitrite-derived nitric oxide occurred without inducing systemic hypotension and has the potential to relieve focal ischemia and preserve tissue vitality by enhancing O2 delivery.
Referent control and motor equivalence of reaching from standing
Authors: Tomita Yosuke , Feldman Anatol G. , Levin Mindy F. 
Published: October 2016

Motor actions may result from central changes in the referent body configuration, defined as the body posture at which muscles begin to be activated or deactivated. The actual body configuration deviates from the referent configuration, particularly because of body inertia and environmental forces. Within these constraints, the system tends to minimize the difference between these configurations. For pointing movement, this strategy can be expressed as the tendency to minimize the difference between the referent trajectory (RT) and actual trajectory (QT) of the effector (hand). This process may underlie motor equivalent behavior that maintains the pointing trajectory regardless of the number of body segments involved. We tested the hypothesis that the minimization process is used to produce pointing in standing subjects. With eyes closed, 10 subjects reached from a standing position to a remembered target located beyond arm length. In randomly chosen trials, hip flexion was unexpectedly prevented, forcing subjects to take a step during pointing to prevent falling. The task was repeated when subjects were instructed to intentionally take a step during pointing. In most cases, reaching accuracy and trajectory curvature were preserved due to adaptive condition-specific changes in interjoint coordination. Results suggest that referent control and the minimization process associated with it may underlie motor equivalence in pointing.NEW & NOTEWORTHY Motor actions may result from minimization of the deflection of the actual body configuration from the centrally specified referent body configuration, in the limits of neuromuscular and environmental constraints. The minimization process may maintain reaching trajectory and accuracy regardless of the number of body segments involved (motor equivalence), as confirmed in this study of reaching from standing in young healthy individuals. Results suggest that the referent control process may underlie motor equivalence in reaching.
The relationship between ERP components and EEG spatial complexity in a visual Go/Nogo task
Authors: Jia Huibin , Li Huayun , Yu Dongchuan 
Published: October 2016

The ERP components and variations of spatial complexity or functional connectivity are two distinct dimensions of neurophysiological events in the visual Go/Nogo task. Extensive studies have been conducted on these two distinct dimensions; however, no study has investigated whether these two neurophysiological events are linked to each other in the visual Go/Nogo task. The relationship between spatial complexity of electroencephalographic (EEG) data, quantified by the measure omega complexity, and event-related potential (ERP) components in a visual Go/Nogo task was studied. We found that with the increase of spatial complexity level, the latencies of N1 and N2 component were shortened and the amplitudes of N1, N2, and P3 components were decreased. The anterior Go/Nogo N2 effect and the Go/Nogo P3 effect were also found to be decreased with the increase of EEG spatial complexity. In addition, the reaction times in high spatial complexity trials were significantly shorter than those of medium and low spatial complexity trials when the time interval used to estimate the EEG spatial complexity was extended to 0∼1,000 ms after stimulus onset. These results suggest that high spatial complexity may be associated with faster cognitive processing and smaller postsynaptic potentials that occur simultaneously in large numbers of cortical pyramidal cells of certain brain regions. The EEG spatial complexity is closely related with demands of certain cognitive processes and the neural processing efficiency of human brain.NEW & NOTEWORTHY The reaction times, the latencies/amplitudes of event-related potential (ERP) components, the Go/Nogo N2 effect, and the Go/Nogo P3 effect are linked to the electroencephalographic (EEG) spatial complexity level. The EEG spatial complexity is closely related to demands of certain cognitive processes and could reflect the neural processing efficiency of human brain. Obtaining the single-trial ERP features through single-trial spatial complexity may be a more efficient approach than traditional methods.
Evidence of common and separate eye and hand accumulators underlying flexible eye-hand coordination
Authors: Jana Sumitash , Gopal Atul , Murthy Aditya 
Published: October 2016

Eye and hand movements are initiated by anatomically separate regions in the brain, and yet these movements can be flexibly coupled and decoupled, depending on the need. The computational architecture that enables this flexible coupling of independent effectors is not understood. Here, we studied the computational architecture that enables flexible eye-hand coordination using a drift diffusion framework, which predicts that the variability of the reaction time (RT) distribution scales with its mean. We show that a common stochastic accumulator to threshold, followed by a noisy effector-dependent delay, explains eye-hand RT distributions and their correlation in a visual search task that required decision-making, while an interactive eye and hand accumulator model did not. In contrast, in an eye-hand dual task, an interactive model better predicted the observed correlations and RT distributions than a common accumulator model. Notably, these two models could only be distinguished on the basis of the variability and not the means of the predicted RT distributions. Additionally, signatures of separate initiation signals were also observed in a small fraction of trials in the visual search task, implying that these distinct computational architectures were not a manifestation of the task design per se. Taken together, our results suggest two unique computational architectures for eye-hand coordination, with task context biasing the brain toward instantiating one of the two architectures.NEW & NOTEWORTHY Previous studies on eye-hand coordination have considered mainly the means of eye and hand reaction time (RT) distributions. Here, we leverage the approximately linear relationship between the mean and standard deviation of RT distributions, as predicted by the drift-diffusion model, to propose the existence of two distinct computational architectures underlying coordinated eye-hand movements. These architectures, for the first time, provide a computational basis for the flexible coupling between eye and hand movements.
Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer: Results from the Finnish Maternity Cohort
Authors: Fortner Renée T. , Schock Helena , Kaaks Rudolf , Lehtinen Matti , Pukkala Eero , Lakso Hans-Åke , Tanner Minna , Kallio Raija , Joensuu Heikki , Korpela Jaana , Toriola Adetunji T. , Hallmans Göran , Grankvist Kjell , Zeleniuch-Jacquotte Anne , Toniolo Paolo , Lundin Eva , Surcel Heljä-Marja 
Published: October 2016

Abstract
Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case–control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case–control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (&lt;140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41 years). hCG was measured using a solid-phase competitive chemiluminescence assay. Odds ratios (OR) were calculated using conditional logistic regression. We observed no association between hCG and breast cancer risk, overall [Quartile 4 vs. 1, OR, 1.14; 95% confidence interval (CI), 0.94–1.39], by estrogen and progesterone receptor status, or by ages at first-term birth or diagnosis. Associations did not differ by time between pregnancy and diagnosis (e.g., &lt;5 years, ORQ4 vs. Q1, 1.10; 95% CI, 0.64–1.89; ≥15 years, ORQ4 vs. Q1, 1.36; 95% CI, 0.86–2.13; pheterogeneity = 0.62). This large prospective study does not support an inverse relationship between early pregnancy serum hCG concentrations and breast cancer risk. Cancer Res; 77(1); 134–41. ©2016 AACR.
Real-life treatment of venous thromboembolism with direct oral anticoagulants: The influence of recommended dosing and regimens
Authors: Trujillo-Santos Javier , Micco Pierpaolo Di , Dentali Francesco , Douketis James , Díaz-Peromingo José Antonio , Núñez Manuel Jesús , Cañas Inmaculada , Mastroiacovo Daniela , De Sousa Marta Saraiva , Monreal Manuel ,   RIETE Investigators
Published: October 2016

SummaryIn patients with venous thromboembolism (VTE), the influence on outcome of using direct oral anticoagulants (DOACs) at non-recommended doses or regimens (once vs twice daily) has not been investigated yet. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the outcomes in patients with VTE receiving DOACs according to the recommendations of the product label versus in those receiving non-recommended doses and/or regimens. The major outcomes were the rate of VTE recurrences, major bleeding and death during the course of therapy. As of March 2016, 1635 VTE patients had received DOACs for initial therapy and 1725 for long-term therapy. For initial therapy, 287 of 1591 patients (18 %) on rivaroxaban and 22 of 44 (50 %) on apixaban did not receive the recommended therapy. For long-term therapy, 217 of 1611 patients (14 %) on rivaroxaban, 29 of 81 (36 %) on apixaban and 15 of 33 (46 %) on dabigatran did not receive the recommended therapy. During the course of therapy with DOACs, eight patients developed VTE recurrences, 14 had major bleeding and 13 died. Patients receiving DOACs at non-recommended doses and/or regimens experienced a higher rate of VTE recurrences (adjusted HR: 10.5; 95 %CI: 1.28–85.9) and a similar rate of major bleeding (adjusted HR: 1.04; 95 %CI: 0.36–3.03) or death (adjusted HR: 1.41; 95 %CI: 0.46–4.29) than those receiving the recommended doses and regimens. In our cohort, a non-negligible proportion of VTE patients received non-recommended doses and/or regimens of DOACs. This use may be associated with worse outcomes.
The Hippo pathway regulates human megakaryocytic differentiation
Authors: Lorthongpanich Chanchao , Jiamvoraphong Nittaya , Supraditaporn Kantpitchar , Klaihmon Phatchanat , U-pratya Yaowalak , Issaragrisil Surapol 
Published: October 2016

SummaryThe Hippo pathway is involved in several biological processes in both flies and mammals. Recent studies have shown that the Hippo pathway regulates Drosophila’s haematopoiesis; however, understanding of its role in mammalian haematopoiesis is still limited. In flies, deletion of the Hippo component gene, Warts, affects crystal cell differentiation. We explored the role of the Hippo pathway in human haemato-poiesis focusing on megakaryopoiesis. To investigate the role of LATS1/2 (a mammalian homolog of Warts) in human megakaryo -blastic cell differentiation and platelet formation, megakaryoblastic cell (MEG-01) line was used as a model to gain insight into mechan-ism of the Hippo pathway in mammalian megakaryopoiesis. Effect of LATS1/2 on megakaryoblastic cell differentiation and platelet production were determined by functional changes. We found that depletion of LATS1/2 resulted in an increase of CD41+ megakaryocytes with impaired platelet biogenesis. Our study shows that the Hippo signalling pathway plays a crucial role in human megakaryoblastic cell differentiation and thrombopoiesis.Supplementary Material to this article is available online at www.thrombosis-online.com.
JUDICIALIZAÇÃO DA SAÚDE E DIÁLOGO INSTITUCIONAL: A EXPERIÊNCIA DE LAGES (SC)
Authors: Asensi Felipe , Pinheiro Roseni 
Published: October 2016

A judicialização do direito à saúde tende a ser pensada sob o prisma da propositura de ações judiciais, mas existe uma série de estratégias extrajudiciais que podem ser desenvolvidas com a presença do Judiciário. O objetivo deste artigo consiste em analisar a interação entre o Judiciário, os profissionais de saúde e a gestão na efetivação do direito à saúde. Para tal, foi realizada uma pesquisa em parceria com o Conselho Nacional de Justiça em 2013 e 2014 no município de Lages (SC), que buscou analisar as estratégias locais desenvolvidas. A experiência de Lages versou sobre o Núcleo de Conciliação de Medicamentos ou que, a partir da interação com o Consórcio Intermunicipal e com os atores políticos e jurídicos, passou a ser ferramenta de diálogo institucional. Esses arranjos permitiram uma atuação predominantemente extrajudicial e fomentaram o diálogo entre os diversos atores locais. O resultado foi a redução da litigiosidade e a ampliação de arranjos institucionais dialógicos.