Nicotinamide adenine dinucleotide (NAD
) is an essential cofactor for redox enzymes, but also moonlights as a substrate for signaling enzymes. When used as a substrate by signaling enzymes, it is ...consumed, necessitating the recycling of NAD
consumption products (i.e., nicotinamide) via a salvage pathway in order to maintain NAD
homeostasis. A major family of NAD
consumers in mammalian cells are poly-ADP-ribose-polymerases (PARPs). PARPs comprise a family of 17 enzymes in humans, 16 of which catalyze the transfer of ADP-ribose from NAD
to macromolecular targets (namely, proteins, but also DNA and RNA). Because PARPs and the NAD
biosynthetic enzymes are subcellularly localized, an emerging concept is that the activity of PARPs and other NAD
consumers are regulated in a compartmentalized manner. In this review, I discuss NAD
metabolism, how different subcellular pools of NAD
are established and regulated, and how free NAD
levels can control signaling by PARPs and redox metabolism.
The optical properties of organic semiconductors are almost exclusively described using the Frenkel exciton picture. In this description, the strong Coulombic interaction between an excited electron ...and the charged vacancy it leaves behind (a hole) is automatically taken into account. If, in an optical microcavity, the exciton-photon interaction is strong compared to the excitonic and photonic decay rates, a second quasiparticle, the microcavity polariton, must be introduced to properly account for this coupling. Coherent, laser-like emission from polaritons has been predicted to occur when the ground-state occupancy of polaritons left angle bracketngs right angle bracket, reaches 1 (ref. 3). This process, known as polariton lasing, can occur at thresholds much lower than required for conventional lasing. Polaritons in organic semiconductors are highly stable at room temperature, but to our knowledge, there has as yet been no report of nonlinear emission from these structures. Here, we demonstrate polariton lasing at room temperature in an organic microcavity composed of a melt-grown anthracene single crystal sandwiched between two dielectric mirrors.
Under the right conditions, cavity polaritons form a macroscopic condensate in the ground state. The fascinating nonlinear behaviour of this condensate is largely dictated by the strength of ...polariton-polariton interactions. In inorganic semiconductors, these result principally from the Coulomb interaction between Wannier-Mott excitons. Such interactions are considerably weaker for the tightly bound Frenkel excitons characteristic of organic semiconductors and were notably absent in the first reported demonstration of organic polariton lasing. In this work, we demonstrate the realization of an organic polariton condensate, at room temperature, in a microcavity containing a thin film of 2,7-bis9,9-di(4-methylphenyl)-fluoren-2-yl-9,9-di(4-methylphenyl)fluorene. On reaching threshold, we observe the spontaneous formation of a linearly polarized condensate, which exhibits a superlinear power dependence, long-range order and a power-dependent blueshift: a clear signature of Frenkel polariton interactions.
Although many studies have reported on tests of the vestibular system a valid and reliable, evidence-based screening battery for easy clinical use remains elusive. Many screening tests attempt to ...assess the vestibulo-ocular reflex. Therefore, head shaking, the Dix-Hallpike maneuver, the supine roll test, and head impulse tests are discussed. Other tests address the spatial orientation functions of the vestibular system, such as the Bucket Test and the Fukuda Stepping test. Still, other tests are based on the known correlates with balance skills, both static and dynamic, such as tandem walking and the modern variation of the Romberg test, the modified Clinical Test of Sensory Interaction and Balance. This review provides a critical overview of the literature on some of these tests and their value for clinical use and in epidemiological studies.
How Viruses Invade Cells Cohen, Fredric S.
Biophysical journal,
03/2016, Letnik:
110, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Every so often news about a viral outbreak goes viral and catches widespread public attention in the media. Human immunodeficiency virus (HIV), West Nile virus, avian influenza (bird flu), Ebola, ...Middle East respiratory virus, and Zika virus have each become, in a flurry of headlines and broadcasts and interviews, the focus of the media's spotlight. And then, like other crises, they fade from view leaving the public with a new health concern to worry about but little knowledge of the actual factors involved in the problem.
Although only a handful of organic materials have shown polariton condensation, their study is rapidly becoming more accessible. The spontaneous appearance of long-range spatial coherence is often ...recognized as a defining feature of such condensates. In this Letter, we study the emergence of spatial coherence in an organic microcavity and demonstrate a number of unique features stemming from the peculiarities of this material set. Despite its disordered nature, we find that correlations extend over the entire spot size, and we measure g(1)(r,r') values of nearly unity at short distances and of 50% for points separated by nearly 10 μm . We show that for large spots, strong shot-to-shot fluctuations emerge as varying phase gradients and defects, including the spontaneous formation of vortices. These are consistent with the presence of modulation instabilities. Furthermore, we find that measurements with flat-top spots are significantly influenced by disorder and can, in some cases, lead to the formation of mutually incoherent localized condensates.
Combination prevention for COVID-19 Cohen, Myron S; Corey, Lawrence
Science (American Association for the Advancement of Science),
05/2020, Letnik:
368, Številka:
6491
Journal Article
Recenzirano
Odprti dostop
The coronavirus disease 2019 (COVID-19) pandemic has produced the fear and disorder inevitably provoked by emerging pathogens. As such, it should also inspire consideration of our experience with HIV ...over the past 40 years. As with HIV, the road to reducing infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19), and attendant morbidity and mortality, requires medical and nonmedical strategies. The most important lesson learned from tackling HIV is to use a combination of prevention strategies.
Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing ...the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.
Staphylococcus aureus USA300 strains cause a highly inflammatory necrotizing pneumonia. The virulence of this strain has been attributed to its expression of multiple toxins that have diverse targets ...including ADAM10, NLRP3 and CD11b. We demonstrate that induction of necroptosis through RIP1/RIP3/MLKL signaling is a major consequence of S. aureus toxin production. Cytotoxicity could be prevented by inhibiting either RIP1 or MLKL signaling and S. aureus mutants lacking agr, hla or Hla pore formation, lukAB or psms were deficient in inducing cell death in human and murine immune cells. Toxin-associated pore formation was essential, as cell death was blocked by exogenous K+ or dextran. MLKL inhibition also blocked caspase-1 and IL-1β production, suggesting a link to the inflammasome. Rip3(-/-) mice exhibited significantly improved staphylococcal clearance and retained an alveolar macrophage population with CD200R and CD206 markers in the setting of acute infection, suggesting increased susceptibility of these leukocytes to necroptosis. The importance of this anti-inflammatory signaling was indicated by the correlation between improved outcome and significantly decreased expression of KC, IL-6, TNF, IL-1α and IL-1β in infected mice. These findings indicate that toxin-induced necroptosis is a major cause of lung pathology in S. aureus pneumonia and suggest the possibility of targeting components of this signaling pathway as a therapeutic strategy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this paper, we propose a novel coupled dictionary training method for single-image super-resolution (SR) based on patchwise sparse recovery, where the learned couple dictionaries relate the low- ...and high-resolution (HR) image patch spaces via sparse representation. The learning process enforces that the sparse representation of a low-resolution (LR) image patch in terms of the LR dictionary can well reconstruct its underlying HR image patch with the dictionary in the high-resolution image patch space. We model the learning problem as a bilevel optimization problem, where the optimization includes an ℓ 1 -norm minimization problem in its constraints. Implicit differentiation is employed to calculate the desired gradient for stochastic gradient descent. We demonstrate that our coupled dictionary learning method can outperform the existing joint dictionary training method both quantitatively and qualitatively. Furthermore, for real applications, we speed up the algorithm approximately 10 times by learning a neural network model for fast sparse inference and selectively processing only those visually salient regions. Extensive experimental comparisons with state-of-the-art SR algorithms validate the effectiveness of our proposed approach.
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