bluuebunny/crossref_metadata_2025_split huggingface dataset:
The deletion of M4 muscarinic receptors increases motor activity in females in the dark phase
Authors: Valuskova Paulina , Forczek Sandor T. , Farar Vladimir , Myslivecek Jaromir 
Published: July 2018

AbstractObjectivesM4 muscarinic receptors (MR) presumably play a role in motor coordination. Previous studies have shown different results depending on genetic background and number of backcrosses. However, no attention has been given to biorhythms.Material and MethodsWe therefore analyzed biorhythms under a light/dark cycle obtained telemetrically in intact animals (activity, body temperature) in M4KO mice growth on the C57Bl6 background using ChronosFit software. Studying pure effects of gene knockout in daily rhythms is especially important knowledge for pharmacological/behavioral studies in which drugs are usually tested in the morning.ResultsWe show that M4KO mice motor activity does not differ substantially from wild‐type mice during light period while in the dark phase (mice active part of the day), the M4KO mice reveal biorhythm changes in many parameters. Moreover, these differences are sex‐dependent and are evident in females only. Mesor, night–day difference, and night value were doubled or tripled when comparing female KO versus male KO. Our in vitro autoradiography demonstrates that M4MR proportion represents 24% in the motor cortex (MOCx), 30% in the somatosensory cortex, 50% in the striatum, 69% in the thalamus, and 48% in the intergeniculate leaflet (IGL). The M4MR densities were negligible in the subparaventricular zone, the posterior hypothalamic area, and in the suprachiasmatic nuclei.ConclusionsWe conclude that cholinergic signaling at M4MR in brain structures such as striatum, MOCx, and probably with the important participation of IGL significantly control motor activity biorhythm. Animal activity differs in the light and dark phases, which should be taken into consideration when interpreting the results.
A High‐Voltage Electrochemical Cell Operating with Two Aqueous Electrolytes of Different pH Values
Authors: Ratajczak Paula , Béguin François 
Published: July 2018

AbstractA concept of a carbon/carbon electrochemical cell using aqueous electrolytic solutions of potassium hydroxide and sodium sulfate as catholyte and anolyte, respectively, and a cation exchange membrane as separator is presented. Owing to the pH difference between the two electrolytes, the theoretical potential difference between water oxidation and reduction is enlarged. Experimentally, an optimized cell could be charged up to 1.5 V, while the operating potential range of the electrodes fitted in the thermodynamic stability limits of the electrolytes. The cell demonstrated a good life span, with constant capacitance and resistance values, when it was kept at imposed voltage of 1.5 V for a total number of 120 hours.
Mechanisms and Regulation of Intestinal Phosphate Absorption
Authors: Hernando Nati , Wagner Carsten A. 
Published: July 2018

ABSTRACTStates of hypo‐ and hyperphosphatemia have deleterious consequences including rickets/osteomalacia and renal/cardiovascular disease, respectively. Therefore, the maintenance of appropriate plasma levels of phosphate is an essential requirement for health. This control is executed by the collaborative action of intestine and kidney whose capacities to (re)absorb phosphate are regulated by a number of hormonal and metabolic factors, among them parathyroid hormone, fibroblast growth factor 23, 1,25(OH)2vitamin D3, and dietary phosphate. The molecular mechanisms responsible for the transepithelial transport of phosphate across enterocytes are only partially understood. Indeed, whereas renal reabsorption entirely relies on well‐characterized active transport mechanisms of phosphate across the renal proximal epithelia, intestinal absorption proceeds via active and passive mechanisms, with the molecular identity of the passive component still unknown. The active absorption of phosphate depends mostly on the activity and expression of the sodium‐dependent phosphate cotransporter NaPi‐IIb (SLC34A2), which is highly regulated by many of the factors, mentioned earlier. Physiologically, the contribution of NaPi‐IIb to the maintenance of phosphate balance appears to be mostly relevant during periods of low phosphate availability. Therefore, its role in individuals living in industrialized societies with high phosphate intake is probably less relevant. Importantly, small increases in plasma phosphate, even within normal range, associate with higher risk of cardiovascular disease. Therefore, therapeutic approaches to treat hyperphosphatemia, including dietary phosphate restriction and phosphate binders, aim at reducing intestinal absorption. Here we review the current state of research in the field. © 2017 American Physiological Society.Compr Physiol8:1065‐1090, 2018.
Platelet‐Activation Mechanisms and Vascular Remodeling
Authors: Rubenstein David A. , Yin Wei 
Published: July 2018

ABSTRACTThis overview article for theComprehensive Physiologycollection is focused on detailing platelets, how platelets respond to various stimuli, how platelets interact with their external biochemical environment, and the role of platelets in physiological and pathological processes. Specifically, we will discuss the four major functions of platelets: activation, adhesion, aggregation, and inflammation. We will extend this discussion to include various mechanisms that can induce these functional changes and a discussion of some of the salient receptors that are responsible for platelets interacting with their external environment. We will finish with a discussion of how platelets interact with their vascular environment, with a special focus on interactions with the extracellular matrix and endothelial cells, and finally how platelets can aid and possibly initiate the progression of various vascular diseases. Throughout this overview, we will highlight both the historical investigations into the role of platelets in health and disease as well as some of the more current work. Overall, the authors aim for the readers to gain an appreciation for the complexity of platelet functions and the multifaceted role of platelets in the vascular system. © 2017 American Physiological Society.Compr Physiol8:1117‐1156, 2018.
Role of Short Chain Fatty Acid Receptors in Intestinal Physiology and Pathophysiology
Authors: Priyadarshini Medha , Kotlo Kumar U. , Dudeja Pradeep K. , Layden Brian T. 
Published: July 2018

ABSTRACTNutrient sensing is a mechanism for organisms to sense their environment. In larger animals, including humans, the intestinal tract is a major site of nutrient sensing for the body, not surprisingly, as this is the central location where nutrients are absorbed. In the gut, bacterial fermentation results in generation of short chain fatty acids (SCFAs), a class of nutrients, which are sensed by specific membrane bound receptors, FFA2, FFA3, GPR109a, and Olfr78. These receptors are expressed uniquely throughout the gut and signal through distinct mechanisms. To date, the emerging data suggests a role of these receptors in normal and pathological conditions. The overall function of these receptors is to regulate aspects of intestinal motility, hormone secretion, maintenance of the epithelial barrier, and immune cell function. Besides in intestinal health, a prominent role of these receptors has emerged in modulation of inflammatory and immune responses during pathological conditions. Moreover, these receptors are being revealed to interact with the gut microbiota. This review article updates the current body of knowledge on SCFA sensing receptors in the gut and their roles in intestinal health and disease as well as in whole body energy homeostasis. © 2017 American Physiological Society.Compr Physiol8:1091‐1115, 2018.
Demonstration of viability and fertility and development of a molecular tool to identify YY supermales in a fish with both genotypic and environmental sex determination
Authors: Hattori Ricardo Shohei , Tashiro Seiya , Zhang Yan , Kakuta Naoya , Yokota Masashi , Strüssmann Carlos Augusto , Yamamoto Yoji 
Published: July 2018

AbstractThe pejerrey possesses a genotypic sex determination system driven by the amhy gene and yet shows marked temperature‐dependent sex determination. Sex‐reversed XY females have been found in a naturally breeding population established in Lake Kasumigaura, Japan. These females could mate with normal XY males and generate YY “supermale” individuals that, if viable and fertile, would sire only genotypic male offspring. This study was conducted to verify the viability, gender, and fertility of YY pejerrey and to develop a molecular method for their identification. Production of YY fish was attempted by crossing a thermally sex‐reversed XY female and an XY male, and rearing the progeny until sexual maturation. To identify the presumable YY individuals, we first conducted a PCR analysis using amhy‐specific primers to screen only amhy‐positive (XY and YY) fish. This screening showed that 60.6% of the progeny was amhy‐positive, which suggested the presence of YY fish. We then conducted a second screening by qPCR in order to identify the individuals with two amhy copies in their genome. This screening revealed 13 individuals, all males, with values twice higher than the other 30 amhy‐positive fishes, suggesting they have a YY complement. This assumption as well as the viability, fertility, and “supermale” nature of these individuals was confirmed in progeny tests with XX females that yielded 100% amhy‐positive offspring. These results demonstrate that qPCR can obviate progeny test as a means to identify the genotypic sex and therefore may be useful for the survey of all three possible genotypes in wild populations.
The use of systematic reviews to justify anaesthesiology trials: A meta‐epidemiological study
Authors: Engelking A. , Cavar M. , Puljak L. 
Published: July 2018

AbstractAimsNew randomized clinical trials (RCTs) should be initiated if previous systematic reviews (SRs) indicate that new trials are needed. We analysed whether RCTs published in anaesthesiology journals mentioned previous SRs as a rationale for conducting trial and for discussing results.MethodsThis was a meta‐epidemiological, descriptive cross‐sectional study. We analysed RCTs published in the seven first‐quartile anaesthesiology journals between 2014 and 2016. We studied text and bibliography of the RCTs to assess whether the authors made a reference to previous SRs when justifying the need for their own clinical trial and discussing the results.ResultsIn the 622 studied RCTs 126 (20%) mentioned verbatim or cited one or more SRs as justification for conducting a trial, most commonly in introduction of a manuscript. Almost half of the included RCTs (44%) did not cite a single systematic review. There was no significant difference between the years in the number of explicitly mentioned SRs as justification for conducting a trial (F = 0.540, p = 0.583). Trials citing, mentioning or explicitly using SRs as a justification were published in journals with significantly higher impact factor and included significantly higher number of participants, while there was no difference in using SRs in trials in terms of funding type, type of intervention or positive versus negative results.ConclusionsTrialists should use evidence from existing SRs for planning a trial, while ethics committees, peer‐reviewers and editors should require authors to provide evidence that a new trial is indeed necessary.SignificanceSince less than a fifth of trials published in high‐impact journals in the field of anaesthesiology explicitly mention previous systematic review as a justification for conducting the trial, authors, ethics committees, editors and peer‐reviewers need to increase their awareness of the need for proper justification regarding the necessity for a new trial.
Nondental orofacial pain in dental practices – diagnosis, therapy and self‐assessment of German dentists and dental students
Authors: Ziegeler C. , Wasiljeff K. , May A. 
Published: July 2018

AbstractBackgroundPatients with non‐dental orofacial pain syndromes will often primarily consult general dentists and other dental specialists. Early and correct diagnosis and therapy is crucial to prevent chronification.MethodsWe assessed the experience of dentists (general dentists and dental specialists; n = 533) and knowledge level of dental students (n = 130) on the diagnosis and treatment of non‐dental orofacial pain. We used an anonymized survey containing 14 items with the four main themes (1) prescription patterns, (2) treatment strategies in non‐dental orofacial pain, (3) interdisciplinary cooperation, and (4) self‐assessment of knowledge as well as post‐graduate education.ResultsNinety‐two percent of dental students stated that they feel either ‘not at all’ (56%) or only ‘somewhat’ (36%) prepared for the diagnosis or treatment of non‐dental orofacial pain. Only 23% of the dentists reported ‘good’ or ‘very good’ confidence for the diagnosis of non‐dental orofacial pain. NSAID were the analgesics of choice when the pain is unspecific (25%) or even neuralgic (10%). Dentists referred patients with non‐dental orofacial pain mostly to ENT‐physicians (59%), oral and maxillofacial surgeons (54%) or TMD specialists (51%).ConclusionInterdisciplinary pain treatment seems to be well acknowledged, however, with a focus on referral within the community of dental specialists. Dental curricula and post‐graduate trainings need to implement the diagnosis and treatment options of non‐dental orofacial pain.
Temporal changes in characteristics and outcomes among pregnant women with pre‐gestational diabetes
Authors: Alessi Janine , Wiegand Daniela M. , Hirakata Vânia N. , Oppermann Maria L.R. , Reichelt Angela J. 
Published: July 2018

AbstractObjectiveTo evaluate pregnancy outcomes among women with pre‐gestational diabetes.MethodsRetrospective analysis of pregnant women with type 1 or type 2 diabetes attending a university hospital in Brazil. Maternal characteristics and pregnancy outcomes were compared among deliveries between May 1, 2005, and December 31, 2010, and between January 1, 2011, and December 31, 2015. Risks were calculated by Poisson regression.ResultsIn total 220 women were included. Type 1 diabetes was more frequent in 2005–2010 than in 2011–2015, and type 2 diabetes was more frequent in 2011–2015 (P=0.005). History of macrosomia (P=0.011), hypertensive disorders of pregnancy (P=0.015), and pre‐gestational excess weight (body mass index >25 kg/m2; P=0.003) was more frequent in 2011–2015. For women with type 1 diabetes, pre‐gestational weight (P=0.007) and glycated hemoglobin (P=0.026) were higher in 2011–2015. For women with type 2 diabetes, previous hypertensive disorders of pregnancy (P=0.032) were more prevalent and family history of diabetes (P<0.001) less prevalent in 2011–2015. Adverse pregnancy outcomes were similar for type 1 and type 2, and across both periods.ConclusionType 2 diabetes became more common over the two time periods and women with type 1 diabetes had higher pre‐gestational weight. Perinatal outcomes were similar.
Managing Awareness in a CURVE‐y World: Agile Systems Engineering for Autonomous Vehicles
Authors: Schindel Bill 
Published: July 2018

ABSTRACTAwareness is vital to agility. Based on an INCOSE agile systems engineering case study, this article illustrates different perspectives on enabling, exploiting, and balancing awareness, including issues of networks versus hierarchies, teaming and leadership, pattern exploitation, model uncertainty, and optimal estimation and control. The SPAWAR System Center Pacific (SSC‐Pac) in San Diego, US‐CA established capability to facilitate agile development of unmanned systems. As a case study in the INCOSE Agile Systems Engineering Life Cycle Model (ASELCM) Discovery Project, SSC‐Pac provided an example of agility challenges and issues of awareness in addressing them. The model‐based ASELCM Pattern helped us analyze this example beyond the context of agile software methods.
Integrating SysML and Agent‐Based Modeling for Rapid Architecture Evaluation
Authors: Maheshwari Apoorv , Raz Ali K. , DeLaurentis Daniel A. , Murphy Andrew , Kolawole Oluwatomi 
Published: July 2018

ABSTRACTIn the face of the changing operational requirements and demands for new capabilities, it often is necessary for systems architects to make substantial changes in a system's architecture. However, traditional systems engineering processes, where architects finalized architecture during the initial concept development stages and engineers develop system simulations during later lifecycle phases, do not support a rapid architecture evolution. In this article, we propose a model‐based systems engineering (MBSE) process to facilitate the rapid evaluation of changes in systems architecture and/or design artifacts for complex systems. This process specifies the minimum set of information that engineers need to include in systems architecture using SysML diagrams with traceability between the diagrams and the agent‐based simulation (ABS) models of a complex system. By integrating SysML and ABS models early in the development lifecycle, teams can readily trace any future evolution of systems architecture represented by the SysML diagrams to changes in an ABS model and hence can rapidly evaluate the impact of architectural evolution. We demonstrate the application of the proposed process using a NASA‐sponsored case study for developing ab initio architectures of the National Airspace System (NAS) where we achieved significant time savings in developing an ABS model of evolving NAS architecture based on SysML‐ABS integration.
Value of routine duodenal mucosal biopsies in the evaluation of anemia in a large Australian referral centre
Authors: Young Edward , Ooi Marie , Nguyen Nam Q 
Published: July 2018

Background and AimSmall bowel mucosal biopsies (SBBx) are routinely performed to investigate unexplained anemia; however, previous studies have demonstrated a low yield in diagnosing celiac disease. Our aim was to determine the yield of routine SBBx in a large cohort of patients who underwent gastroscopy for the investigation of anemia.MethodsData from consecutive patients who underwent gastroscopy for the investigation of anemia in a tertiary hospital, from January 2008–December 2011, were prospectively collected. Measured outcomes were the prevalence of celiac disease, the yield of duodenal biopsies, and the correlation between celiac serology and diagnosis.ResultsOver 4 years, 987 patients (385 M:602 F; 48.27 ± 15.89 years) underwent endoscopy for anemia, of which 534 (54.1%) had proven iron deficiency anemia (IDA). Abnormal SBBx consistent with celiac disease were found in 2% (22/987), with a higher prevalence in females (3.2%, n = 19 vs 0.8%, n = 3 in males) and in those with IDA (3.6%, n = 19 vs 0.7%, n = 3 in non‐IDA). Macroscopic endoscopic abnormalities were present in 86% (19/22) of patients with celiac disease. Of the 178 patients who had celiac serology, tissue transglutaminase antibody had the highest sensitivity (80%) and specificity (99%). Combined serology had a sensitivity of 85.7%.ConclusionOnly 2% of patients with unexplained anemia had abnormal SBBx consistent with celiac disease and even fewer patients in non‐IDA. Given the availability and high sensitivity of celiac serology and macroscopic changes on endoscopy, SBBx should not be routine during endoscopy but should be limited to those with positive celiac serology, abnormal endoscopic appearance, or females with IDA.
Effect of counterface on cartilage boundary lubricating ability by proteoglycan 4 and hyaluronan: Cartilage‐glass versus cartilage–cartilage
Authors: Abubacker Saleem , McPeak Allison , Dorosz Sam G. , Egberts Philip , Schmidt Tannin A. 
Published: July 2018

ABSTRACTThe objective of this study was to determine the effect of different sliding interface materials (counterface) on the cartilage lubricating ability of proteoglycan 4 (PRG4) and hyaluronan (HA) by measuring the kinetic coefficient of friction on cartilage‐glass and cartilage–cartilage interfaces over a wide range of sliding velocities. The lubrication properties of PRG4 and HA were assessed at cartilage‐glass and cartilage–cartilage interfaces using a previously described test setup with a stationary area of contact. Samples were articulated at varying effective sliding velocities of 10, 3, 1, 0.3, 0.1, and 0.01 mm/s. The response of PRG4 and HA as effective friction‐reducing cartilage boundary lubricants was varied and was dependent primarily on the test counterface. At a physiological cartilage–cartilage interface both HA and PRG4 effectively reduced friction compared to PBS at slower speeds while at higher speeds PRG4 was similar to PBS, and HA similar to SF. Conversely, at a cartilage‐glass interface HA demonstrated no friction reducing ability compared to PBS, and PRG4 appeared just as effective as SF. Cartilage‐glass friction coefficients were also significantly greater than cartilage–cartilage friction coefficients. These results indicate the in vitro friction coefficient of putative cartilage boundary lubricants can be affected by the test counterface and suggest that use of synthetic surfaces in studying cartilage boundary lubrication may not always be appropriate for all molecules of interest. As such, care should be taken when interpreting such data, specifically when comparing to in vitro data obtained at a cartilage–cartilage interface, and especially when extrapolating to in vivo situations. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2923–2931, 2018.
Expression of Francisella pathogenicity island protein intracellular growth locus E (IglE) in mammalian cells is involved in intracellular trafficking, possibly through microtubule organizing center
Authors: Shimizu Takashi , Otonari Shiho , Suzuki Jin , Uda Akihiko , Watanabe Kenta , Watarai Masahisa 
Published: July 2018

AbstractFrancisella tularensis is the causative agent of the infectious disease tularemia and is designated a category A bioterrorism agent. The type VI secretion system encoded by the Francisella pathogenicity island (FPI) is necessary for intracellular growth; however, the functions of FPI proteins are largely unknown. In this study, we found that the FPI protein intracellular growth locus E (IglE) showed a unique localization pattern compared to other FPI proteins. Deleting iglE from Francisella tularensis subsp. novicida (F. novicida) decreased intracellular growth. Immunoprecipitation and pull‐down assays revealed that IglE was associated with β‐tubulin. Additionally, GFP‐fused IglE colocalized with microtubule organizing centers (MTOCs) in 293T cells. The iglE deletion mutant was transferred with dynein toward MTOCs and packed into lysosome‐localizing areas. Conversely, the wild‐type F. novicida exhibited intracellular growth distant from MTOCs. In addition, IglE expressed in 293T cells colocalized with dynein. These results suggest that IglE helps to prevent dynein‐ and MTOC‐mediated intracellular trafficking in host cells to inhibit the transport of F. novicida toward lysosomes.