Differentiating cells tailor their metabolism to fulfill their specialized functions. We examined whether mitochondrial fusion is important for metabolic tailoring during spermatogenesis. Acutely ...after depletion of mitofusins
and
, spermatogenesis arrests due to failure to accomplish a metabolic shift during meiosis. This metabolic shift includes increased mitochondrial content, mitochondrial elongation, and upregulation of oxidative phosphorylation (OXPHOS). With long-term mitofusin loss, all differentiating germ cell types are depleted, but proliferation of stem-like undifferentiated spermatogonia remains unaffected. Thus, compared with undifferentiated spermatogonia, differentiating spermatogonia and meiotic spermatocytes have cell physiologies that require high levels of mitochondrial fusion. Proteomics in fibroblasts reveals that mitofusin-null cells downregulate respiratory chain complexes and mitochondrial ribosomal subunits. Similarly, mitofusin depletion in immortalized spermatocytes or germ cells in vivo results in reduced OXPHOS subunits and activity. We reveal that by promoting OXPHOS, mitofusins enable spermatogonial differentiation and a metabolic shift during meiosis.
Attributes and predictors of long COVID Sudre, Carole H; Murray, Benjamin; Varsavsky, Thomas ...
Nature Medicine,
04/2021, Letnik:
27, Številka:
4
Journal Article, Magazine Article
Recenzirano
Odprti dostop
Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a ...protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app
. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.
The development of GaN-on-diamond devices holds much promise for the creation of high-power density electronics. Inherent to the growth of these devices, a dielectric layer is placed between the GaN ...and diamond, which can contribute significantly to the overall thermal resistance of the structure. In this work, we explore the role of different interfaces in contributing to the thermal resistance of the interface of GaN/diamond layers, specifically using 5 nm layers of AlN, SiN, or no interlayer at all. Using time-domain thermoreflectance along with electron energy loss spectroscopy, we were able to determine that a SiN interfacial layer provided the lowest thermal boundary resistance (<10 m2K/GW) because of the formation of an Si–C–N layer at the interface. The AlN and no interlayer samples were observed to have TBRs greater than 20 m2K/GW as a result of a harsh growth environment that roughened the interface (enhancing phonon scattering) when the GaN was not properly protected.
The HR 8799 system uniquely harbors four young super-Jupiters whose orbits can provide insights into the system's dynamical history and constrain the masses of the planets themselves. Using the ...Gemini Planet Imager, we obtained down to one milliarcsecond precision on the astrometry of these planets. We assessed four-planet orbit models with different levels of constraints and found that assuming the planets are near 1:2:4:8 period commensurabilities, or are coplanar, does not worsen the fit. We added the prior that the planets must have been stable for the age of the system (40 Myr) by running orbit configurations from our posteriors through N-body simulations and varying the masses of the planets. We found that only assuming the planets are both coplanar and near 1:2:4:8 period commensurabilities produces dynamically stable orbits in large quantities. Our posterior of stable coplanar orbits tightly constrains the planets' orbits, and we discuss implications for the outermost planet b shaping the debris disk. A four-planet resonance lock is not necessary for stability up to now. However, planet pairs d and e, and c and d, are each likely locked in two-body resonances for stability if their component masses are above 6 MJup and 7 MJup, respectively. Combining the dynamical and luminosity constraints on the masses using hot-start evolutionary models and a system age of 42 5 Myr, we found the mass of planet b to be 5.8 0.5 MJup, and the masses of planets c, d, and e to be each.
In this phase 2 study, peginterferon-free regimens were effective in patients with hepatitis C virus genotype 1 infection.
Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, ...liver cancer, and end-stage liver disease.
1
The current standard of care for chronic HCV genotype 1 infection is pegylated interferon (peginterferon) and ribavirin, with a protease inhibitor (boceprevir or telaprevir).
2
Although the addition of a protease inhibitor has been associated with a significant increase in response rates, only approximately one third of patients who had not had a response to prior therapy with peginterferon and ribavirin had a sustained virologic response when re-treated with the addition of a protease inhibitor.
3
,
4
Furthermore, these therapies are associated with adverse . . .
The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant ...chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism.
Diarylborinic acids (Ar2BOH) catalyze the C3-selective ring opening of 3,4-epoxy alcohols with aniline, dialkylamine and arenethiol nucleophiles. The regiochemical outcome is consistent with a ...catalytic tethering mechanism in which the borinic acid interacts with both the electrophile and the nucleophile. The rate acceleration resulting from this induced intramolecularity effect is sufficient to overcome steric biases that would otherwise favor C4-selective opening of the substituted epoxy alcohols.
Because of their low bandwidth in the phase-encode (PE) direction, the susceptibility-induced off-resonance field causes distortions in echo planar imaging (EPI) images. It is therefore crucial to ...correct for susceptibility-induced distortions when performing diffusion studies using EPI. The susceptibility-induced field is caused by the object (head) disrupting the field and it is typically assumed that it remains constant within a framework defined by the object, (i.e. it follows the object as it moves in the scanner).
However, this is only approximately true. When a non-spherical object rotates around an axis other than that parallel with the magnetic flux (the z-axis) it changes the way it disrupts the field, leading to different distortions. Hence, if using a single field to correct for distortions there will be residual distortions in the volumes where the object orientation is substantially different to that when the field was measured.
In this paper we present a post-processing method for estimating the field as it changes with motion during the course of an experiment. It only requires a single measured field and knowledge of the orientation of the subject when that field was acquired. The volume-to-volume changes of the field as a consequence of subject movement are estimated directly from the diffusion data without the need for any additional or special acquisitions. It uses a generative model that predicts how each volume would look predicated on field change and inverts that model to yield an estimate of the field changes. It has been validated on both simulations and experimental data. The results show that we are able to track the field with high accuracy and that we are able to correct the data for the adverse effects of the changing field.
Chalcogen bonding is the noncovalent interaction between an electron-deficient, covalently bonded chalcogen (Te, Se, S) and a Lewis base. Although substantial evidence supports the existence of ...chalcogen bonding in the solid state, quantitative data regarding the strengths of the interactions in the solution phase are lacking. Herein, determinations of the association constants of benzotelluradiazoles with a variety of Lewis bases (Cl–, Br–, I–, NO3 – and quinuclidine, in organic solvent) are described. The participation of the benzotelluradiazoles in chalcogen bonding interactions was probed by UV–vis, 1H and 19F NMR spectroscopy as well as nano-ESI mass spectrometry. Trends in the free energy of chalcogen bonds upon variation of the donor, acceptor and solvent are evident from these data, including a linear free energy relationship between chalcogen bond donor ability and calculated electrostatic potential at the tellurium center. Calculations using the dispersion-corrected B97-D3 functional were found to give good agreement with the experimental free energies of chalcogen bonding.
In the presence of an arylboronic acid and a hydrogen atom transfer mediator under photoredox conditions, furanoside derivatives undergo site-selective redox isomerizations to ...2-keto-3-deoxyfuranosides. Experimental evidence and computational modeling suggest that the transformation takes place by abstraction of the hydrogen atom from the 2-position of the furanoside-derived arylboronic ester, followed by C3-O bond cleavage
via
spin-center shift. This mechanism is reminiscent of the currently accepted pathway for the formation of 3′-ketodeoxynucleotides by ribonucleotide reductase enzymes.
The combined action of boronic acid, photoredox catalyst and hydrogen atom transfer mediator enables the transformation of furanosides to 2-keto-3-deoxyfuranosides, a synthetic analog of the process catalyzed by the ribonucleotide reductase enzymes.
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