On Iron Metabolism and Its Regulation Vogt, Anne-Cathrine S; Arsiwala, Tasneem; Mohsen, Mona ...
International journal of molecular sciences,
04/2021, Letnik:
22, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Iron is a critical metal for several vital biological processes. Most of the body's iron is bound to hemoglobin in erythrocytes. Iron from senescent red blood cells is recycled by macrophages in the ...spleen, liver and bone marrow. Dietary iron is taken up by the divalent metal transporter 1 (DMT1) in enterocytes and transported to portal blood via ferroportin (FPN), where it is bound to transferrin and taken up by hepatocytes, macrophages and bone marrow cells via transferrin receptor 1 (TfR1). While most of the physiologically active iron is bound hemoglobin, the major storage of most iron occurs in the liver in a ferritin-bound fashion. In response to an increased iron load, hepatocytes secrete the peptide hormone hepcidin, which binds to and induces internalization and degradation of the iron transporter FPN, thus controlling the amount of iron released from the cells into the blood. This review summarizes the key mechanisms and players involved in cellular and systemic iron regulation.
Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs
, it is the closest single star to the Sun; only the ...three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known
and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging
, astrometry
and direct imaging
, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.
Although perceived discrimination (especially due to race-ethnicity) decreases mental health, the influence ofperceived discrimination due to other reasons on mental health needs to be explored. This ...study examines the relationship between perceived age discrimination and mental health and determines whether psychosocial resources explain or buffer (i.e., reduce the strength of) this relationship. Using a nationally-representative sample of persons aged 25–74 from the Midlife Development in the United States survey, this study finds that perceived age discrimination is associated with higher psychological distress and lower positive well-being. Perceived age discrimination is more negatively associated with women's mental health than men's. Although sense of control buffers the relationship between perceived age discrimination and psychological distress, perceived age discrimination decreases sense of control and social support.
Background
SARS‐CoV‐2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock‐downs, wearing masks, and increased hygiene, the ...virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or adenoviruses, has greatly added to our ability to keep the virus at bay; again, however, in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long‐term control of SARS‐CoV‐2 would be inexpensive production at large scale, ability to make multiple booster injections, and long‐term stability at 4℃.
Methods
Here, we describe such a vaccine candidate, consisting of the SARS‐CoV‐2 receptor‐binding motif (RBM) grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMVTT‐RBM.
Results
Using bacterial fermentation and continuous flow centrifugation for purification, the yield of the production process is estimated to be >2.5 million doses per 1000‐litre fermenter run. We demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera. The induced antibodies are more cross‐reactive to mutant RBDs of variants of concern (VoC). Furthermore, antibody responses are neutralizing and long‐lived. In addition, the vaccine candidate was stable for at least 14 months at 4℃.
Conclusion
Thus, the here presented VLP‐based vaccine may be a good candidate for use as conventional vaccine in the long term.
In this study, we describe a novel conventional COVID‐19 vaccine that consists of the RBM of SARS‐CoV‐2 genetically grafted onto the surface of our optimized cucumber‐mosaic virus‐like particles. We demonstrate that the vaccine candidate (mCuMVTT‐RBM) is highly immunogenic in mice and rabbits, can efficiently neutralize SARS‐CoV‐2, and is stable and highly scalable. The induced antibodies show cross‐reactivity with VoC. Abbreviations: COVID‐19, coronavirus disease 2019; CuMVTT‐VLPs, cucumber‐mosaic virus‐like particles; RBD, receptor‐binding domain; RBM, receptor‐binding motif; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; VOCs, variant of concerns.
Exoplanets of a few Earth masses can be now detected around nearby low-mass stars using Doppler spectroscopy. In this Letter, we investigate the radial velocity variations of Kapteyn's star, which is ...both a sub-dwarf M-star and the nearest halo object to the Sun. The observations comprise archival and new HARPS (High Accuracy Radial velocity Planet Searcher), High Resolution Echelle Spectrometer (HIRES) and Planet Finder Spectrograph (PFS) Doppler measurements. Two Doppler signals are detected at periods of 48 and 120 d using likelihood periodograms and a Bayesian analysis of the data. Using the same techniques, the activity indices and archival All Sky Automated Survey (ASAS-3) photometry show evidence for low-level activity periodicities of the order of several hundred days. However, there are no significant correlations with the radial velocity variations on the same time-scales. The inclusion of planetary Keplerian signals in the model results in levels of correlated and excess white noise that are remarkably low compared to younger G, K and M dwarfs. We conclude that Kapteyn's star is most probably orbited by two super-Earth mass planets, one of which is orbiting in its circumstellar habitable zone, becoming the oldest potentially habitable planet known to date. The presence and long-term survival of a planetary system seem a remarkable feat given the peculiar origin and kinematic history of Kapteyn's star. The detection of super-Earth mass planets around halo stars provides important insights into planet-formation processes in the early days of the Milky Way.
A nearby multiplanet system
Exoplanets can interact gravitationally with other objects orbiting the same star, affecting their evolution and stability. Studying these effects requires locating ...systems with multiple planets. Monitoring the nearby red dwarf star GJ 887, Jeffers
et al.
detected periodic radial velocity signals, indicating the presence of two planets on orbits with periods of about 9 and 22 days and a further candidate planet (see the Perspective by Davies). The inclinations of the orbits are unknown, so only minimum masses could be determined, but those were consistent with both planets being super-Earths—more massive than Earth but less than Neptune. This system is only 3.3 parsecs from the Sun, which should facilitate follow-up with other techniques.
Science
, this issue p.
1477
; see also p.
1432
Two super-Earth exoplanets orbit GJ 887, a red dwarf star located only 3.3 parsecs from the Sun.
The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.
In image-guided spine surgery, robust three-dimensional to two-dimensional (3D-2D) registration of preoperative computed tomography (CT) and intraoperative radiographs can be challenged by the image ...content mismatch associated with the presence of surgical instrumentation and implants as well as soft-tissue resection or deformation. This work investigates image similarity metrics in 3D-2D registration offering improved robustness against mismatch, thereby improving performance and reducing or eliminating the need for manual masking. The performance of four gradient-based image similarity metrics (gradient information (GI), gradient correlation (GC), gradient information with linear scaling (GS), and gradient orientation (GO)) with a multi-start optimization strategy was evaluated in an institutional review board-approved retrospective clinical study using 51 preoperative CT images and 115 intraoperative mobile radiographs. Registrations were tested with and without polygonal masks as a function of the number of multistarts employed during optimization. Registration accuracy was evaluated in terms of the projection distance error (PDE) and assessment of failure modes (PDE > 30 mm) that could impede reliable vertebral level localization. With manual polygonal masking and 200 multistarts, the GC and GO metrics exhibited robust performance with 0% gross failures and median PDE < 6.4 mm (±4.4 mm interquartile range (IQR)) and a median runtime of 84 s (plus upwards of 1-2 min for manual masking). Excluding manual polygonal masks and decreasing the number of multistarts to 50 caused the GC-based registration to fail at a rate of >14%; however, GO maintained robustness with a 0% gross failure rate. Overall, the GI, GC, and GS metrics were susceptible to registration errors associated with content mismatch, but GO provided robust registration (median PDE = 5.5 mm, 2.6 mm IQR) without manual masking and with an improved runtime (29.3 s). The GO metric improved the registration accuracy and robustness in the presence of strong image content mismatch. This capability could offer valuable assistance and decision support in spine level localization in a manner consistent with clinical workflow.
Alzheimer's disease (AD) is the most common form of dementia and may contribute to 60-70% of cases. Worldwide, around 50 million people suffer from dementia and the prediction is that the number will ...more than triple by 2050, as the population ages. Extracellular protein aggregation and plaque deposition as well as accumulation of intracellular neurofibrillary tangles, all leading to neurodegeneration, are the hallmarks of brains with Alzheimer's disease. Therapeutic strategies including active and passive immunizations have been widely explored in the last two decades. Several compounds have shown promising results in many AD animal models. To date, only symptomatic treatments are available and because of the alarming epidemiological data, novel therapeutic strategies to prevent, mitigate, or delay the onset of AD are required. In this mini-review, we focus on our understanding of AD pathobiology and discuss current active and passive immunomodulating therapies targeting amyloid-β protein.
Introduction
The pathology of a mucoid degeneration of the anterior cruciate ligament (MDACL) has been mentioned in several publications but due to its rare incidence it is not a well-known ...pathology. Partial or complete resection of the ACL is the option of choice after failed non-surgical treatment. However, the success rate of both surgical techniques and the subsequent risk of an ACL instability is not known. The purpose of this study was to compare the clinical and radiological outcome between partial resection and complete resection of the ACL in patients with MDACL.
Materials and methods
Patients with MDACL verified by MRI and persistent knee pain were treated by partial (Group I) or complete resection (Group II) of the ACL and were included in a controlled clinical trial after unsuccessful conservative treatment for at least 6 months. Demographic, clinical and radiological data including the thickness of ACL, ACL/intercondylar ratio, patient’s age at the time of surgery, the presenting symptoms, range of motion and ligament stability assessed by the ACL ligament score (Lachman test) were collected. In addition, Tegner activity score and Lysholm score were evaluated preoperatively and at final follow-up after a minimum of 12 months.
Results
At final follow-up with a mean of 16.8 ± 8.8 months (range 12–41; Group I: 18.3 ± 9.7 vs. Group II: 15.3 ± 8.0; ns), all patients were pain free. Postoperatively, positive Lachman tests were noted in all patients (100%) in Group II (
n
= 5 patients with grade II and
n
= 5 patients with grade III). In Group I, 8 patients (80%) showed a negative Lachman test (grade I) and 2 patients (20%) a slightly elongated Lachman test with a firm stop (grade II). The mean knee flexion at follow-up examination was 132° ± 7° (range 120°–140°; Group I: 129° ± 9° vs. Group II: 135° ± 4°; ns). In pairwise comparison, flexion angle increased significantly in both groups (Group I:
p
= 0.0124 and Group II:
p
< 0.001). Pairwise comparison of thickness of the ACL and ACL/intercondylar ratio prior to and post-surgery in Group I showed non-significant differences.
Conclusion
Both arthroscopic debridement and complete resection of the ACL lead to improvement of clinical and radiological findings in isolated MDACL. However, complete resection of the ACL will result in higher instability. Therefore, partial resection might be the better treatment option, especially in young patients with MDACL.
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