754 research outputs found
Behavioral metabolution: the adaptive and evolutionary potential of metabolism-based chemotaxis
We use a minimal model of metabolism-based chemotaxis to show how a coupling between metabolism and behavior can affect evolutionary dynamics in a process we refer to as behavioral metabolution. This mutual influence can function as an in-the-moment, intrinsic evaluation of the adaptive value of a novel situation, such as an encounter with a compound that activates new metabolic pathways. Our model demonstrates how changes to metabolic pathways can lead to improvement of behavioral strategies, and conversely, how behavior can contribute to the exploration and fixation of new metabolic pathways. These examples indicate the potentially important role that the interplay between behavior and metabolism could have played in shaping adaptive evolution in early life and protolife. We argue that the processes illustrated by these models can be interpreted as an unorthodox instantiation of the principles of evolution by random variation and selective retention. We then discuss how the interaction between metabolism and behavior can facilitate evolution through (i) increasing exposure to environmental variation, (ii) making more likely the fixation of some beneficial metabolic pathways, (iii) providing a mechanism for in-the-moment adaptation to changes in the environment and to changes in the organization of the organism itself, and (iv) generating conditions that are conducive to speciatio
The results of using a tendon autograft as a new rotator cable for patients with a massive rotator cuff tear:a technical note and comparative outcome analysis
Background: Several surgical reconstructive options are available to treat massive rotator cuff tears (MRCTs). The rotator cable has an important function and we evaluated the clinical result after arthroscopic reconstruction of the rotator cable with an autograft tendon. Methods: A prospective pilot study was performed with inclusion of four patients, average age of 64 years, with an irreparable MRCT. The patients underwent an arthroscopic reconstruction of the rotator cable with the use of the long head of biceps tendon autograft, except for one which was reconstructed with a hamstring tendon. Pre- and postsurgically, the Constant-Murley Score (CMS), Western Ontario Rotator Cuff Index (WORC), Simple Shoulder Test (SST), visual analog scale (VAS) scores, and an MRI was performed. Clinical results of the study group were compared with clinical results of comparable cohort of patients with a MRCT, treated non-operatively with physiotherapy. Results: The CMS score increased after surgery in three of the four patients. The improvement of CMS score was comparable to the improvement of the CMS score encountered in a comparable cohort. The MRI at 12 months follow-up showed that the reconstructed rotator cable was disintegrated in all patients and the rotator cuff was detached and retracted. Conclusions: In our pilot study, arthroscopic reconstruction of the rotator cable using a tendon autograft failed over time and showed no clinical benefit in comparison to the non-operative treatment with physiotherapy. Trial registration: The regional Medical Ethical Committee (Zwolle) gave approval at 14th of October 2016 and assigned no. 16.06100
Arthroscopic isolated long head of biceps tenotomy in patients with degenerative rotator cuff tears:mid-term clinical results and prognostic factors
INTRODUCTION: The long head of biceps tendon is frequently involved in degenerative rotator cuff tears. Therefore, this study explored the clinical results of an isolated biceps tenotomy and identified prognostic factors for improvement in pain and function. MATERIALS AND METHODS: Between 2008 and 2017, an arthroscopic isolated biceps tenotomy was performed on 64 patients with a degenerative rotator cuff tear (> 65 years). Primary outcome was patient-perceived improvement in pain and function. Potential prognostic factors for improvement in pain and function were identified. RESULTS: A perceived improvement in pain was reported in 78% of the patients at three months after surgery and in 75% at a mean follow-up of 4.2 years (1-7 years; n = 55). A perceived improvement in function was observed in 49% of patients at three months and in 76% of patients at follow-up. Patients with a preoperatively normal acromiohumeral distance (> 10 mm) reported an improvement in pain and function significantly more often. Retraction of the supraspinatus tendon Patte 3 was significantly associated with worse functional outcome. CONCLUSIONS: A biceps tenotomy can be a reliable treatment option for patients with symptomatic degenerative cuff tears who fail conservative treatment and have a normal acromiohumeral distance (> 10 mm)
Unsafe testosterone-based dosing regimen of androgen deprivation therapy in patients with locally advanced or metastatic prostate cancer:a prematurely ended randomized controlled trial (MIDAS-trial)
Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone
AbstractThe meiotic cell cycle of mammalian oocytes starts during embryogenesis and then pauses until luteinizing hormone (LH) acts on the granulosa cells of the follicle surrounding the oocyte to restart the cell cycle. An essential event in this process is a decrease in cyclic GMP in the granulosa cells, and part of the cGMP decrease results from dephosphorylation and inactivation of the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase, also known as guanylyl cyclase B. However, it is unknown whether NPR2 dephosphorylation is essential for LH-induced meiotic resumption. Here, we prevented NPR2 dephosphorylation by generating a mouse line in which the seven regulatory serines and threonines of NPR2 were changed to the phosphomimetic amino acid glutamate (Npr2–7E). Npr2–7E/7E follicles failed to show a decrease in enzyme activity in response to LH, and the cGMP decrease was attenuated; correspondingly, LH-induced meiotic resumption was delayed. Meiotic resumption in response to EGF receptor activation was likewise delayed, indicating that NPR2 dephosphorylation is a component of the pathway by which EGF receptor activation mediates LH signaling. We also found that most of the NPR2 protein in the follicle was present in the mural granulosa cells. These findings indicate that NPR2 dephosphorylation in the mural granulosa cells is essential for the normal progression of meiosis in response to LH and EGF receptor activation. In addition, these studies provide the first demonstration that a change in phosphorylation of a transmembrane guanylyl cyclase regulates a physiological process, a mechanism that may also control other developmental events
Extracellular Matrix Stiffness and Composition Regulate the Myofibroblast Differentiation of Vaginal Fibroblasts
Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has different extracellular matrix (ECM) composition than healthy vaginal tissues. In this study, we employed a series of matrices with known stiffnesses, as well as vaginal ECMs, in combination with vaginal fibroblasts from POP and healthy tissues to investigate how matrix stiffness and composition regulate myofibroblast differentiation in vaginal fibroblasts. Stiffness was positively correlated to production of α-smooth muscle actin (α-SMA). Vaginal ECMs induced myofibroblast differentiation as both α-SMA and collagen gene expressions were increased. This differentiation was more pronounced in cells seeded on POP-ECMs that were stiffer than those derived from healthy tissues and had higher collagen and elastin protein content. We showed that stiffness and ECM content regulate vaginal myofibroblast differentiation. We provide preliminary evidence that vaginal fibroblasts might recognize POP-ECMs as scar tissues that need to be remodeled. This is fundamentally important for tissue repair, and provides a rational basis for POP disease modelling and therapeutic innovations in vaginal reconstruction
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Neutron-Absorbing Coatings for Safe Storage of Fissile Materials with Enhanced Shielding & Criticality Safety
Neutron-absorbing Fe-based amorphous-metal coatings have been developed that are more corrosion resistant than other criticality-control materials, including Al-B{sub 4}C composites, borated stainless steels, and Ni-Cr-Mo-Gd alloys. The presence of relatively high concentration of boron in these coatings not only enhances its neutron-absorption capability, but also enables these coatings to exist in the amorphous state. Exceptional corrosion resistance has been achieved with these Fe-based amorphous-metal alloys through additions of chromium, molybdenum, and tungsten. The addition of rare earth elements such as yttrium has lowered the critical cooling rate of these materials, thereby rendering them more easily processed. Containers used for the storage of nuclear materials, and protected from corrosion through the application of amorphous metal coatings, would have greatly enhanced service lives, and would therefore provide greater long-term safety. Amorphous alloy powders have been successfully produced in multi-ton quantities with gas atomization, and applied to several half-scale spent fuel storage containers and criticality control structures with the high-velocity oxy-fuel (HVOF) thermal spray process. Salt fog testing and neutron radiography of these prototypes indicates that such an approach is viable for the production of large-scale industrial-scale facilities and containers. The use of these durable neutron-absorbing materials to coat stainless steel containers and storage racks, as well as vaults, hot-cell facilities and glove boxes could substantially reduce the risk of criticality in the event of an accident. These materials are particularly attractive for shielding applications since they are fire proof. Additionally, layers of other cold and thermal sprayed materials that include carbon and/or carbides can be used in conjunction with the high-boron amorphous metal coatings for the purpose of moderation. For example, various carbides, including boron, tungsten, and chromium carbide, as well as graphite particles can be co-deposited with a metallic binder phase with either thermal spray or cold spray technology. These moderator layers would also be fire resistant. By coating the vessels and piping used for spent fuel reprocessing, including slab and pencil tanks, enhanced criticality safety and substantially better corrosion resistance can be achieved simultaneously. Since these alloys are Fe-based, any substitution of these for high-performance Ni-based alloys is expected to result in a cost savings. Ultimately, the cost of these materials should comparable to that of stainless steels
Characteristics of Interstitial Fibrosis and Inflammatory Cell Infiltration in Right Ventricles of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension
Objective. Systemic sclerosis-associated pulmonary arterial hypertension (SScPAH) has a disturbed function of the right ventricle (RV) when compared to idiopathic PAH (IPAH). Systemic sclerosis may also affect the heart. We hypothesize that RV differences may occur at the level of interstitial inflammation and—fibrosis and compared inflammatory cell infiltrate and fibrosis between the RV of SScPAH, IPAH, and healthy controls.
Methods. Paraffin-embedded tissue samples of RV and left ventricle (LV) from SScPAH (n = 5) and IPAH (n = 9) patients and controls (n = 4) were picrosirius red stained for detection of interstitial fibrosis, which was quantified semiautomatically. Neutrophilic granulocytes (MPO), macrophages (CD68), and lymphocytes (CD45) were immunohistochemically stained and only interstitial leukocytes were counted. Presence of epi- or endocardial inflammation, and of perivascular or intimal fibrosis of coronary arteries was assessed semiquantitatively (0–3: absent to extensive).
Results. RV's of SScPAH showed significantly more inflammatory cells than of IPAH (cells/mm2, mean ± sd MPO 11 ± 3 versus 6 ± 1; CD68 11 ± 3 versus 6 ± 1; CD45 11 ± 1 versus 5 ± 1 , P < .05) and than of controls. RV interstitial fibrosis was similar in SScPAH and IPAH (4 ± 1 versus 5 ± 1%, P = .9), and did not differ from controls (5 ± 1%, P = .8). In 4 SScPAH and 5 IPAH RV's foci of replacement fibrosis were found. No differences were found on epi- or endocardial inflammation or on perivascular or intimal fibrosis of coronary arteries.
Conclusion. SScPAH RVs display denser inflammatory infiltrates than IPAH, while they do not differ with respect to interstitial fibrosis. Whether increased inflammatory status is a contributor to altered RV function in SScPAH warrants further research
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Diurnal/semidiurnal polar motion excited by oceanic tidal angular momentum
The axial component of the oceanic tidal angular momentum (OTAM) has been demonstrated to be responsible for most of the diurnal and semidiurnal variations in Earth's rotational rate. In this paper we study the equatorial components of OTAM and their corresponding effects on the orientation of Earth's rotational axis, or polar motion. Three ocean tide models derived from TOPEX/Poseidon satellite altimetry are employed to predict the polar motion excited by eight major diurnal/semidiurnal tides (Q₁,O₁,P₁, K₁, N₂, M₂, S₂, K₂). The predictions are compared with geodetic measurements of polar motion from both long‐term observations and during the intensive campaign Cont94. The prograde diurnal and prograde and retrograde semidiurnal periods are treated, whereas the retrograde diurnal polar motion is not treated (because it cannot be observed directly and uniquely.) The comparison shows generally good agreement, with discrepancies typically within 10–30 micro‐arc‐ seconds for the largest tides. The eight tides collectively explain nearly 60% of the total variance in subdaily polar motion during Cont94. This establishes the dominant role of OTAM in exciting the diurnal/semidiurnal polar motion and paves the way for detailed studies of short‐period nontidal polar motion. The present accuracy, however, is inadequate to shed light on the prograde diurnal polar libration
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