Recent evidence indicates the number of dopaminergic neurons in the adult rodent hypothalamus and midbrain is regulated by environmental cues, including photoperiod, and that this occurs via up- or ...down-regulation of expression of genes and proteins that are important for dopamine (DA) synthesis in extant neurons ('DA neurotransmitter switching'). If the same occurs in humans, it may have implications for neurological symptoms associated with DA imbalances. Here we tested whether there are differences in the number of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) and DA transporter (DAT) immunoreactive neurons in the midbrain of people who died in summer (long-day photoperiod, n = 5) versus winter (short-day photoperiod, n = 5). TH and DAT immunoreactivity in neurons and their processes was qualitatively higher in summer compared with winter. The density of TH immunopositive (TH+) neurons was significantly (~6-fold) higher whereas the density of TH immunonegative (TH-) neurons was significantly (~2.5-fold) lower in summer compared with winter. The density of total neurons (TH+ and TH- combined) was not different. The density of DAT+ neurons was ~2-fold higher whereas the density of DAT- neurons was ~2-fold lower in summer compared with winter, although these differences were not statistically significant. In contrast, midbrain nuclear volume, the density of supposed glia (small TH- cells), and the amount of TUNEL staining were the same in summer compared with winter. This study provides the first evidence of an association between environmental stimuli (photoperiod) and the number of midbrain DA neurons in humans, and suggests DA neurotransmitter switching underlies this association.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present multiwavelength photometric monitoring of WD 1145+017, a white dwarf exhibiting periodic dimming events interpreted to be the transits of orbiting, disintegrating planetesimals. Our ...observations include the first set of near-infrared light curves for the object, obtained on multiple nights over the span of 1 month, and recorded multiple transit events with depths varying between ~20 and 50 per cent. Simultaneous near-infrared and optical observations of the deepest and longest duration transit event were obtained on two epochs with the Anglo-Australian Telescope and three optical facilities, over the wavelength range of 0.5-1.2 ...m. These observations revealed no measurable difference in transit depths for multiple photometric pass bands, allowing us to place a 2... lower limit of 0.8 ...m on the grain size in the putative transiting debris cloud. This conclusion is consistent with the spectral energy distribution of the system, which can be fit with an optically thin debris disc with minimum particle sizes of 10... ...m. (ProQuest: ... denotes formulae/symbols omitted.)
We investigate the performance of different methodologies that measure the time lag between broad-line and continuum variations in reverberation mapping data using simulated light curves that probe a ...range of cadence, time baseline, and signal-to-noise ratio in the flux measurements. We compare three widely adopted lag-measuring methods: the interpolated cross-correlation function (ICCF), the z-transformed discrete correlation function (ZDCF), and the Markov chain Monte Carlo code JAVELIN, for mock data with qualities typical of multiobject spectroscopic reverberation mapping (MOS-RM) surveys that simultaneously monitor hundreds of quasars. We quantify the overall lag-detection efficiency, the rate of false detections, and the quality of lag measurements for each of these methods and under different survey designs (e.g., observing cadence and depth) using mock quasar light curves. Overall JAVELIN and ICCF outperform ZDCF in essentially all tests performed. Compared with ICCF, JAVELIN produces higher quality lag measurements, is capable of measuring more lags with timescales shorter than the observing cadence, is less susceptible to seasonal gaps and signal-to-noise ratio degradation in the light curves, and produces more accurate lag uncertainties. We measure the Hβ broad-line region size-luminosity (R-L) relation with each method using the simulated light curves to assess the impact of selection effects of the design of MOS-RM surveys. The slope of the R-L relation measured by JAVELIN is the least biased among the three methods and is consistent across different survey designs. These results demonstrate a clear preference for JAVELIN over the other two nonparametric methods for MOS-RM programs, particularly in the regime of limited light-curve quality as expected from most MOS-RM programs.
The 'hot Jupiters' that abound in lists of known extrasolar planets are thought to have formed far from their host stars, but migrate inwards through interactions with the proto-planetary disk from ...which they were born, or by an alternative mechanism such as planet-planet scattering. The hot Jupiters closest to their parent stars, at orbital distances of only ∼0.02 astronomical units, have strong tidal interactions, and systems such as OGLE-TR-56 have been suggested as tests of tidal dissipation theory. Here we report the discovery of planet WASP-18b with an orbital period of 0.94 days and a mass of ten Jupiter masses (10 MJup), resulting in a tidal interaction an order of magnitude stronger than that of planet OGLE-TR-56b. Under the assumption that the tidal-dissipation parameter Q of the host star is of the order of 106, as measured for Solar System bodies and binary stars and as often applied to extrasolar planets, WASP-18b will be spiralling inwards on a timescale less than a thousandth that of the lifetime of its host star. Therefore either WASP-18 is in a rare, exceptionally short-lived state, or the tidal dissipation in this system (and possibly other hot-Jupiter systems) must be much weaker than in the Solar System.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims. Current and upcoming space missions may be able to detect moons of transiting extra-solar planets. In this context it is important to understand if exomoons are expected to exist and what their ...possible properties are. Methods. Using estimates for the stability of exomoon orbits from numerical studies, a list of 87 known transiting exoplanets is tested for the potential to host large exomoons. Results. For 92% of the sample, moons larger than Luna can be excluded on prograde orbits, unless the parent exoplanet's internal structure is very different from the gas-giants of the solar system. Only WASP-24b, OGLE2-TR-L9, CoRoT-3b and CoRoT-9b could have moons above 0.4 $m_\oplus$, which is within the likely detection capabilities of current observational facilities. Additionally, the range of possible orbital radii of exomoons of the known transiting exoplanets, with two exceptions, is below 8 Jupiter-radii and therefore rather small.
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FMFMET, NUK, UL, UM, UPUK
Attempts to repair the central nervous system damaged as a result of trauma or disease will depend on the ability to restore the appropriate neuronal connectivity. This will rely on establishing ...appropriate chemical and physical environments for supporting neural cells and their processes and in this regard, engineering of biomaterials is of increasing interest. It will be important to understand how cells behave on these biomaterials in vitro, prior to future in vivo application. We reveal that modification of 3-dimensional (3D) electrospun poly-epsilon-caprolactone (PCL) nanofiber scaffolds by fiber alignment and aminolysation is superior to classical 2-dimensional (2D) culture-ware in promoting in vitro proliferation and differentiation of cortical cells. Many studies have examined the importance of exogenous soluble factors to promote cell fate specification. Here, we demonstrate that tethering the neurotrophin, brain-derived neurotrophic factor (BDNF), onto modified nanofibers is superior to culturing in the presence of soluble BDNF. Functional immobilization of BDNF to polymer nanofibers enhances neural stem cell (NSC) proliferation and directs cell fate toward neuronal and oligodendrocyte specification, essential for neural tissue repair. These findings indicate that modified PCL nanofibrous 3D scaffolds are capable of supporting NSCs and their derivatives and may present a new avenue for encouraging neural repair in the future.
Abstract Iron deficiency is one of the most common disorders affecting humans, and iron-deficiency anemia continues to represent a major public health problem worldwide. It is especially common among ...women of childbearing age because of pregnancy and menstrual blood loss. Additional patient groups include those with other sources of blood loss, malnutrition, or gut malabsorption. Iron-deficiency anemia remains prevalent despite the widespread ability to diagnose the disease and availability of medicinal iron preparations. Therefore, new approaches are needed to effectively manage these patient populations. In this review, the diagnosis and treatment of iron-deficiency anemia are discussed with emphasis placed on consideration of patient-specific features. It is proposed that all patients participate in their own care by helping their physician to identify a tolerable daily iron dose, formulation, and schedule. Dosing cycles are recommended for iron replacement based on the tolerated daily dose and the total iron deficit. Each cycle consists of 5000 mg of oral elemental iron ingested over at least 1 month with appropriate follow-up. This approach should assist physicians and their patients with the implementation of individualized treatment strategies for patients with iron-deficiency anemia.
Bioenergetic abnormalities and metabolic dysfunctionoccur in amyotrophic lateral sclerosis (ALS) patients and genetic mouse models. However, whether metabolic dysfunction occurs earlyin ALS ...pathophysiology linked to different ALS genes remains unclear.Here, we investigatedAMP-activated protein kinase (AMPK) activation, which is a key enzyme induced by energy depletion and metabolic stress, inneuronal cells and mouse models expressing mutantsuperoxide dismutase 1 (SOD1)or TAR DNA binding protein 43 (TDP-43) linked to ALS.AMPKphosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice at disease onset and accumulated incytoplasmic granules in motor neurons, but not in pre-symptomatic mice. AMPK phosphorylation also occurred in peripheraltissues, liver and kidney, in SOD1G93A mice at disease onset, demonstrating that AMPK activation occurs late and is not restricted to motor neurons. Conversely, AMPK activity was drastically diminished in spinal cords and brains of presymptomatic and symptomatictransgenic TDP-43A315T mice and motor neuronal cells expressing different TDP-43 mutants. We show that mutant TDP-43 induction of the AMPK phosphatase,protein phosphatase 2A (PP2A), is associated with AMPK inactivation in these ALS models. Furthermore, PP2A inhibition by okadaic acid reversed AMPK inactivation by mutant TDP-43 in neuronal cells. Our results suggest that mutant SOD1 and TDP-43 exert contrasting effects on AMPK activation which may reflect key differences in energy metabolism and neurodegeneration in spinal cords of SOD1G93A and TDP-43A315T mice. While AMPK activation in motor neurons correlateswith progressionin mutant SOD1-mediated disease, AMPK inactivation mediated by PP2Ais associated withmutant TDP-43-linked ALS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cu/Zn‐superoxide dismutase is misfolded in familial and sporadic amyotrophic lateral sclerosis, but it is not clear how this triggers endoplasmic reticulum (ER) stress or other pathogenic processes. ...Here, we demonstrate that mutant SOD1 (mSOD1) is predominantly found in the cytoplasm in neuronal cells. Furthermore, we show that mSOD1 inhibits secretory protein transport from the ER to Golgi apparatus. ER‐Golgi transport is linked to ER stress, Golgi fragmentation and axonal transport and we also show that inhibition of ER‐Golgi trafficking preceded ER stress, Golgi fragmentation, protein aggregation and apoptosis in cells expressing mSOD1. Restoration of ER‐Golgi transport by over‐expression of coatomer coat protein II subunit Sar1 protected against inclusion formation and apoptosis, thus linking dysfunction in ER‐Golgi transport to cellular pathology. These findings thus link several cellular events in amyotrophic lateral sclerosis into a single mechanism occurring early in mSOD1 expressing cells.
Cu/Zn‐superoxide dismutase (SOD1) is misfolded in familial and sporadic Amyotrophic Lateral Sclerosis, but it is unclear how this triggers endoplasmic reticulum (ER) stress and other cellular events. Here, we show that mutant SOD1 inhibits protein transport from the ER to Golgi apparatus prior to ER stress, Golgi fragmentation and apoptosis, and restoration of transport prevents inclusion formation and apoptosis. COPII: coatomer coat protein II.
Cu/Zn‐superoxide dismutase (SOD1) is misfolded in familial and sporadic Amyotrophic Lateral Sclerosis, but it is unclear how this triggers endoplasmic reticulum (ER) stress and other cellular events. Here, we show that mutant SOD1 inhibits protein transport from the ER to Golgi apparatus prior to ER stress, Golgi fragmentation and apoptosis, and restoration of transport prevents inclusion formation and apoptosis. COPII: coatomer coat protein II.
Cover Image for this issue: doi: 10.1111/jnc.12549.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tidal turbines are one source of marine renewable energy but development of tidal power is hampered by uncertainties in fish-turbine interaction impacts. Current knowledge gaps exist in efforts to ...quantify risks, as empirical data and modeling studies have characterized components of fish approach and interaction with turbines, but a comprehensive model that quantifies conditional occurrence probabilities of fish approaching and then interacting with a turbine in sequential steps is lacking. We combined empirical acoustic density measurements of Pacific herring (
Clupea pallasii
) and when data limited, published probabilities in an impact probability model that includes approach, entrainment, interactions, and avoidance of fish with axial or cross-flow tidal turbines. Interaction impacts include fish collisions with stationary turbine components, blade strikes by rotating blades, and/or a collision followed by a blade strike. Impact probabilities for collision followed by a blade strike were lowest with estimates ranging from 0.0000242 to 0.0678, and highest for blade strike ranging from 0.000261 to 0.40. Maximum probabilities occurred for a cross-flow turbine at night with no active or passive avoidance. Estimates were lowest when probabilities were conditional on sequential events, and when active and passive avoidance was included for an axial-flow turbine during the day. As expected, conditional probabilities were typically lower than analogous independent events and literature values. Estimating impact probabilities for Pacific herring in Admiralty Inlet, Washington, United States for two device types illustrates utilization of existing data and simultaneously identifies data gaps needed to fully calculate empirical-based probabilities for any site-species combination.
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