Evolution of AANAT: expansion of the gene family in the cephalochordate amphioxus

<p>Abstract</p> <p>Background</p> <p>The arylalkylamine <it>N</it>-acetyltransferase (AANAT) family is divided into structurally distinct vertebrate and non-vertebrate groups. Expression of vertebrate AANATs is limited primarily to the pineal gland and retina, where it plays a role in controlling the circadian rhythm in melatonin synthesis. Based on the role melatonin plays in biological timing, AANAT has been given the moniker "the Timezyme". Non-vertebrate AANATs, which occur in fungi and protists, are thought to play a role in detoxification and are not known to be associated with a specific tissue.</p> <p>Results</p> <p>We have found that the amphioxus genome contains seven <it>AANAT</it>s, all having non-vertebrate type features. This and the absence of <it>AANATs </it>from the genomes of Hemichordates and Urochordates support the view that a major transition in the evolution of the <it>AANATs </it>may have occurred at the onset of vertebrate evolution. Analysis of the expression pattern of the two most structurally divergent <it>AANAT</it>s in <it>Branchiostoma lanceolatum </it>(<it>bl</it>) revealed that they are expressed early in development and also in the adult at low levels throughout the body, possibly associated with the neural tube. Expression is clearly not exclusively associated with the proposed analogs of the pineal gland and retina. blAANAT activity is influenced by environmental lighting, but light/dark differences do not persist under constant light or constant dark conditions, indicating they are not circadian in nature. bfAANATα and bfAANATδ' have unusually alkaline (> 9.0) optimal pH, more than two pH units higher than that of vertebrate AANATs.</p> <p>Conclusions</p> <p>The substrate selectivity profiles of bfAANATα and δ' are relatively broad, including alkylamines, arylalkylamines and diamines, in contrast to vertebrate forms, which selectively acetylate serotonin and other arylalkylamines. Based on these features, it appears that amphioxus AANATs could play several roles, including detoxification and biogenic amine inactivation. The presence of seven AANATs in amphioxus genome supports the view that arylalkylamine and polyamine acetylation is important to the biology of this organism and that these genes evolved in response to specific pressures related to requirements for amine acetylation.</p

What factors promote student resilience on a level 1 distance learning module?

Resilience is understood to be the ability to adapt positively in the face of adversity. In relation to new students on a distance learning module, this can mean how they adapt and make sense of the demands of their chosen study to enable them to persist in their studies. This article reports a small-scale study involving semistructured telephone interviews with students on a level 1 distance learning module at the UK Open University. Students identified the challenges they experienced such as carving out time to study alongside other commitments, as well as developing their academic writing. Students also identified factors that enabled them to adapt to these challenges and be successful in continuing to study. Students rated highly the support they received from tutors in the form of tailored, detailed feedback on their assignments. Other factors that enabled students to persist in their studies were time management, self-belief and motivation

Testing the running of the cosmological constant with Type Ia Supernovae at high z

Within the Quantum Field Theory context the idea of a "cosmological constant" (CC) evolving with time looks quite natural as it just reflects the change of the vacuum energy with the typical energy of the universe. In the particular frame of Ref.[30], a "running CC" at low energies may arise from generic quantum effects near the Planck scale, M_P, provided there is a smooth decoupling of all massive particles below M_P. In this work we further develop the cosmological consequences of a "running CC" by addressing the accelerated evolution of the universe within that model. The rate of change of the CC stays slow, without fine-tuning, and is comparable to H^2 M_P^2. It can be described by a single parameter, \nu, that can be determined from already planned experiments using SNe Ia at high z. The range of allowed values for \nu follow mainly from nucleosynthesis restrictions. Present samples of SNe Ia can not yet distinguish between a "constant" CC or a "running" one. The numerical simulations presented in this work show that SNAP can probe the predicted variation of the CC either ruling out this idea or confirming the evolution hereafter expected.Comment: LaTeX, 51 pages, 13 figures, 1 table, references added, typos corrected, version accepted in JCA

GEA 3162, a peroxynitrite donor, induces Bcl-2-sensitive, p53-independent apoptosis in murine bone marrow cells

AbstractApoptosis may be regulated by oxidants such as peroxynitrite (ONOO−). The tumour suppressor, p53, has been reported to play a crucial role in apoptosis induced by oxidants, therefore we assessed the ability of a ONOO− donor, GEA 3162, to activate caspases and induce mitochondrial permeability in a p53-deficient murine bone marrow cell line, Jaws II. Furthermore, these cells were stably transfected with Bcl-2, in order to investigate the impact of this survival protein on ONOO−-induced apoptosis. GEA 3162 activated caspases and induced loss of mitochondrial membrane potential in Jaws II cells. In particular, caspases 3 and 2 were activated, alongside minor activation of caspases 8 and 9, and apoptosis was partially dependent upon p38 MAP kinase activation, with little or no role for JNK. Overexpression of Bcl-2 abolished activation of all caspases and reduced the change in mitochondrial membrane potential. Thus, we have demonstrated that the ONOO− donor, GEA 3162, induces apoptosis in Jaws II murine myeloid cells despite lacking functional p53, via a pathway that principally involves caspases 2 and 3 and mitochondrial changes. This is blocked by overexpression of Bcl-2 via a mechanism that does not appear to merely reflect stabilisation of the mitochondrial membrane

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205

The nocturnal increase in circulating melatonin in vertebrates is regulated by the activity of arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the melatonin pathway (serotonin → N-acetylserotonin → melatonin). Large changes in activity are linked to cyclic AMP-dependent protein kinase-mediated phosphorylation of AANAT T31. Phosphorylation of T31 promotes binding of AANAT to the dimeric 14-3-3 protein, which activates AANAT by increasing arylalkylamine affinity. In the current study, a putative second AANAT cyclic AMP-dependent protein kinase phosphorylation site, S205, was found to be ≈55% phosphorylated at night, when T31 is ≈40% phosphorylated. These findings indicate that ovine AANAT is dual-phosphorylated. Moreover, light exposure at night decreases T31 and S205 phosphorylation, consistent with a regulatory role of both sites. AANAT peptides containing either T31 or S205 associate with 14-3-3ζ in a phosphorylation-dependent manner; binding through phosphorylated (p)T31 is stronger than that through pS205, consistent with the location of only pT31 in a mode I binding motif, one of two recognized high-affinity 14-3-3-binding motifs AANAT protein binds to 14-3-3ζ through pT31 or pS205. Two-site binding lowers the K(m) for arylalkylamine substrate to ≈30 μM. In contrast, single-site pS205 binding increases the K(m) to ≈1,200 μM. Accordingly, the switch from dual to single pS205 binding of AANAT to 14-3-3 changes the K(m) for substrates by ≈40-fold. pS205 seems to be part of a previously unrecognized 14-3-3-binding motif-pS/pT (X(1–2))-COOH, referred to here as mode III