Background: Studies show that high phosphotidylinositol 3,4,5-trisphosphate (PIP sub(3)) promotes cytoskeletal rearrangements and alters cell motility and chemotaxis, possibly through activation of ...protein kinase Bs (PKBs). However, chemotaxis can still occur in the absence of PIP sub(3), and the identities of the PIP sub(3)-independent pathways remain unknown. Results: Here, we outline a PIP sub(3)-independent pathway linking temporal and spatial activation of PKBs by Tor complex 2 (TorC2) to the chemotactic response. Within seconds of stimulating Dictyostelium cells with chemoattractant, two PKB homologs, PKBA and PKBR1, mediate transient phosphoryla-tion of at least eight proteins, including Talin, PI4P 5-kinase, two Ras GEFs, and a RhoGap. Surprisingly, all of the substrates are phosphorylated with normal kinetics in cells lacking PI 3-kinase activity. Cells deficient in TorC2 or PKB activity show reduced phosphorylation of the endogenous substrates and are impaired in chemotaxis. The PKBs are activated through phosphorylation of their hydrophobic motifs via TorC2 and subsequent phosphorylation of their activation loops. These chemoattractant-inducible events are restricted to the cell's leading edge even in the absence of PIP sub(3). Activation of TorC2 depends on heterotrimeric G protein function and intermediate G proteins, including Ras GTPases. Conclusions: The data lead to a model where cytosolic TorC2, encountering locally activated small G protein(s) at the leading edge of the cell, becomes activated and phosphorylates PKBs. These in turn phosphorylate a series of signaling and cytoskeletal proteins, thereby regulating directed migration.
Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to ...thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients.
We studied 16 patients (8 females, aged 29-68 years) with active acromegaly and 12 control subjects (7 females, 24-65 years). All participants were tested with TRH (400 microg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between -30 and 120 min for GH and PRL determinations, and between -30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis.
Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any significant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a significant (P<0.05) increase in PRL concentrations at 15-120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were significantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were significantly lower in patients than in controls. Infusion with rhEPO modified neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers.
Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modified by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.
This contribution reevaluates the circuit prototype of tunable diplexers based on the `dual-manifold' concept. The targeted application are diplexers whose channel center frequencies can be ...arbitrarily positioned, resulting in contiguous and non-contiguous channel spacing.
ABSTRACT This work aimed to describe the origin, distribution, and ramifications of the ischiadicus nerve in the giant anteater and to provide anatomical data which could explain not only the ...evolutionary aspects but also provide important information for other related works. For the present study, four specimens were used, prepared by perfusion of 10% formaldehyde solution via the femoral artery, for conservation and dissection. The origin of the right and left ischiadicus nerves in the giant anteater from the ventral ramification of the third lumbar (L3) and the first (S1), second (S2), and third (S3) sacral spinal nerves. These nerves were symmetrical in all animals studied. The distribution and ramification occurred to the superficial, middle, and deep gluteal, gemelli, piriform, quadratus femoris, tensor fasciae latae, caudal crural abductor, cranial and caudal parts of the biceps femoris, adductor, semitendinous, and cranial and caudal parts of the semimembranous muscles. Based on the origins of the ischiadicus nerves, there is a caudal migration in the nerve location in animals in a more recent position on the evolutionary scale due to reconfiguration of the lumbosacral plexus, resulting from the increase in a number of lumbar vertebrae. There is no complete homology of the muscle innervation.
RESUMO Objetivou-se descrever as origens, distribuições e ramificações dos nervos isquiáticos no tamanduá-bandeira, disponibilizando, assim, dados anatômicos que possam não só elucidar os aspectos evolutivos como também fornecer informações importantes para áreas afins. Foram utilizados quatro espécimes preparados por meio da perfusão de formaldeído 10% via artéria femoral, para conservação e dissecação. As origens dos nervos isquiáticos direito e esquerdo no tamanduá-bandeira foram provenientes dos ramos ventrais dos nervos espinhais lombares três e sacrais um, dois e três, sendo simétricos em todos os animais estudados. As distribuições e ramificações ocorreram nos músculos glúteos superficial, médio e profundo; gêmeo; piriforme; quadrado femoral; tensor da fáscia lata; abdutor crural caudal; bíceps femoral parte cranial; bíceps femoral parte caudal; adutor; semitendíneo; semimembranáceo parte cranial e semimembranáceo parte caudal. Notou-se que houve uma migração caudal na localização deste nervo nos animais mais recentes na escala evolutiva, devido a uma reconfiguração do plexo lombossacral decorrente do aumento no número de vértebras lombares, não havendo uma homologia total quanto à inervação dos músculos.
One of the most important concerns within the field of urban hydraulic engineers is the right management of water resources. When there is more than one water source, there is a question that must be ...answered: How much water should be provided by each water source according to the demand curve of the network? This work proposes a methodology that solves this question. It involves an energy analysis of the water network based on the concept of the setpoint curve. The setpoint curve gives, for every supplied flow, the minimum head needed to satisfy pressure requirements in the network. In this sense, the setpoint curve of every source relates two variables: supplied flow and minimum required head. Energy consumption in every source is evaluated by means of the product of these two variables. Then flow distribution among sources is optimized and minimum heads are obtained from the setpoint curve. The optimization process has been validated in two different ways. On one hand, a discrete method has been used, where a predefined combination of flow distributions are evaluated. On the other hand, the solution is found by means of Hooke-Jeeves and Nelder-Mead optimization algorithms. To apply these methods EPANET and its Toolkit has been applied to the mathematical model of the network. The optimization process can be applied to networks models with and without leakages. Finally, the methodology is applied to two cases, one academic network and real network where maximum flow limitations of every sources were also taken into account.
Examination of the internal genital apparatus of Apristurus longicephalus, a small, deep‐water bottom‐dwelling catshark (Scyliorhinidae) from the western Pacific and Indian Oceans has revealed that ...it is a hermaphroditic species. It possesses both the developed genital apparatus of one sex and the undeveloped genital apparatus of the opposite sex in the same individual. Apristurus longicephalus is the first case of normal hermaphroditism to be recorded in cartilaginous fishes and this has been further classified as rudimentary hermaphroditism.
Abstract
Background/Aims
Shared decision-making (SDM) is a joint process in which a person and healthcare professional work together to reach decisions about care. The Improving uptake of Fracture ...Prevention drug treatments (iFraP) study developed a prototype theoretically-informed intervention consisting of a computerised decision aid (DA) and Fracture Liaison Service (FLS) clinician training package to improve SDM about osteoporosis medicines. This abstract focuses on the early prototype iFraP in-practice testing phase that explored perceived acceptability of iFraP by those using it, barriers to, and facilitators of, implementation of the prototype iFraP in practice, and necessary changes required ahead of a full-scale randomised controlled trial (RCT).
Methods
In-practice testing was conducted at one FLS site. Participating FLS clinicians completed the prototype iFraP clinician training package, covering enhanced communication skills (e.g SDM, risk communication and health literacy techniques). Consenting patients with a recent fragility fracture referred for an FLS consultation were eligible to participate. Three cycles of iFraP in-practice testing were completed. Each cycle included observed iFraP consultations and post-consultation patient think-aloud interviews. After each complete cycle, the FLS clinician(s) was interviewed. Data were analysed using a framework approach. The Theoretical Framework of Acceptability and Theoretical Domains Framework facilitated understanding of iFraP acceptability and barriers to, and facilitators of, implementation.
Results
Four FLS clinicians (3 nurses, 1 allied health professional) completed the iFraP clinician training and delivered 10 iFraP consultations (8 face-to-face, 2 telephone) using the iFraP DA with participating patients (n = 3 cycle 1; n = 3 cycle 2; n = 4 cycle 3). In total, the four FLS clinicians completed 7 interviews, with all 10 patients completing a post-consultation interview. Findings demonstrate that patients and clinicians perceived the prototype iFraP DA as acceptable. Clinicians suggested that the iFraP DA supported them to elicit and address patient perceptions, increase patient involvement, and provide patients with sufficient and accessible information. Patients and clinicians expressed wanting to use iFraP in future FLS appointments, with some clinicians continuing to use the DA outside of iFraP in-practice testing. Identified barriers included: some clinicians questioned both the use of iFraP DA with patients not recommended first-line drug treatment; and, expressed concern that iFraP DA could extend the consultation length. Our findings demonstrated necessary updates to meet user needs and overcome identified barriers to iFraP intervention use, including presentation and structural changes to support integration of the iFraP DA into the consultation flow. Clinicians also provided feedback to improve the training package, including the need to demonstrate the DA in use, and increased allocated time to practice using the DA.
Conclusion
The iFraP intervention was perceived as acceptable, with the potential to support SDM about osteoporosis medicines. The iFraP RCT will now test our improved iFraP intervention across 3 FLS sites in England.
Disclosure
L. Bullock: None. N. Tyler: None. M. Thompson: None. S. Ryan: Grants/research support; the General Nursing Council for England and Wales Trust. J. Lefroy: None. S. Leyland: None. J. Fleming: None. E.M. Clark: None. S. Thomas: Other; owns Prescribing Decision Support Ltd that developed the iFraP decision aid. C. Gidlow: None. C.P. Iglesias-Urrutia: None. T.W. O'Neill: Grants/research support; supported by the NIHR Manchester Biomedical Research Centre. C.D. Mallen: Grants/research support; funded by the NIHR Applied Research Collaboration West Midlands, funded by the NIHR School for Primary Care Research. C. Jinks: Grants/research support; part funded by NIHR Applied Research Collaboration (ARC) West Midlands. Z. Paskins: Grants/research support; funded by the National Institute for Health Research (NIHR) Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy.
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