Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn ...from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions.
We present adaptive optics-assisted integral field spectroscopy around the Hα or Hβ lines of 12 gravitationally lensed galaxies obtained with VLT/SINFONI, Keck/OSIRIS and Gemini/NIFS. We combine ...these data with previous observations and investigate the dynamics and star formation properties of 17 lensed galaxies at 1 < z < 4. Thanks to gravitational magnification of 1.4–90 times by foreground clusters, effective spatial resolutions of 40–700 pc are achieved. The magnification also allows us to probe lower star formation rates (SFRs) and stellar masses than unlensed samples; our target galaxies feature dust-corrected SFRs derived from Hα or Hβ emission of ∼0.8–40 M⊙ yr−1, and stellar masses M
* ∼ 4 × 108–6 × 1010 M⊙. All of the galaxies show velocity gradients, with 59 per cent consistent with being rotating discs and a likely merger fraction of 29 per cent, with the remaining 12 per cent classed as ‘undetermined’. We extract 50 star-forming clumps with sizes in the range 60 pc–1 kpc from the Hα (or Hβ) maps, and find that their surface brightnesses, Σclump and their characteristic luminosities, L
0, evolve to higher luminosities with redshift. We show that this evolution can be described by fragmentation on larger scales in gas-rich discs, and is likely to be driven by evolving gas fractions.
Integrins are components of cell-matrix adhesions, and function as scaffolds for various signal transduction pathways. So far no lipid ligand for integrin has been reported. Here we show that a ...lipid, oxysterol 25-hydroxycholesterol (25HC), directly binds to α5β1 and αvβ3 integrins to activate integrin-focal adhesion kinase (FAK) signaling. Treatment of macrophages and epithelial cells with 25HC results in an increase in activated αvβ3 integrin in podosome and focal adhesion matrix adhesion sites. Moreover, activation of pattern recognition receptor on macrophages induces secretion of 25HC, triggering integrin signaling and the production of proinflammatory cytokines such as TNF and IL-6. Thus, the lipid molecule 25HC is a physiologically relevant activator of integrins and is involved in positively regulating proinflammatory responses. Our data suggest that extracellular 25HC links innate immune inflammatory response with integrin signaling.
The LHCb simulation application, Gauss, consists of two independent phases, the generation of the primary event and the tracking of particles produced in the experimental setup. For the LHCb ...experimental program it is particularly important to model B meson decays: the EvtGen code developed in CLEO and BABAR has been chosen and customized for non-coherent B production as occuring in pp collisions at the LHC. The initial proton-proton collision is provided by a different generator engine, currently PYTHIA 6 for massive production of signal and generic pp collisions events. Beam gas events, background events originating from proton halo, cosmics and calibration events for different detectors can be generated in addition to pp collisions. Different generator packages as available in the physics community or specifically developed in LHCb are used for the different purposes. Running conditions affecting the generated events such as the size of the luminous region, the number of collisions occuring in a bunch crossing and the number of spill-over events from neighbouring bunches are modeled via dedicated algorithms appropriately configured. The design of the generator phase of Gauss will be described: a modular structure with well defined interfaces specific to the various tasks, e.g. pp collisions, particle decays, selections, etc. has been chosen. Different implementations are available for the various tasks allowing selecting and combining them as most appropriate at run time as in the case of PYTHIA 6 for pp collisions or HIJING for beam gas. The advantages of such structure, allowing for example to adopt transparently new generators packages, will be discussed.
The coexistence of different mating strategies, whereby a species can reproduce both by selfing and outcrossing, is an evolutionary enigma. Theory predicts two predominant stable mating states: ...outcrossing with strong inbreeding depression or selfing with weak inbreeding depression. As these two mating strategies are subject to opposing selective forces, mixed breeding systems are thought to be a rare transitory state yet can persist even after multiple speciation events. We hypothesise that if each mating strategy plays a distinctive role during some part of the species life history, opposing selective pressures could be balanced, permitting the stable co-existence of selfing and outcrossing sexual morphs. In this scenario, we would expect each morph to be specialised in their respective roles. Here we show, using behavioural, physiological and gene expression studies, that the selfing (hermaphrodite) and outcrossing (female) sexual morphs of the trioecious nematode Auanema freiburgensis have distinct adaptations optimised for their different roles during the life cycle. A. freiburgensis hermaphrodites are known to be produced under stressful conditions and are specialised for dispersal to new habitat patches. Here we show that they exhibit metabolic and intestinal changes enabling them to meet the cost of dispersal and reproduction. In contrast, A. freiburgensis females are produced in favourable conditions and facilitate rapid population growth. We found that females compensate for the lack of reproductive assurance by reallocating resources from intestinal development to mate-finding behaviour. The specialisation of each mating system for its role in the life cycle could balance opposing selective forces allowing the stable maintenance of both mating systems in A. freiburgensis.
Laminins are structural components of basement membranes. In addition, they are key extracellular-matrix regulators of cell adhesion, migration, differentiation and proliferation. This Commentary ...focuses on a relatively understudied aspect of laminin biology: how is laminin deposited into the extracellular matrix? This topic has fascinated researchers for some time, particularly considering the diversity of patterns of laminin that can be visualized in the matrix of cultured cells. We discuss current ideas of how laminin matrices are assembled, the role of matrix receptors in this process and how laminin-associated proteins modulate matrix deposition. We speculate on the role of signaling pathways that are involved in laminin-matrix deposition and on how laminin patterns might play an important role in specifying cell behaviors, especially directed migration. We conclude with a description of new developments in the way that laminin deposition is being studied, including the use of tagged laminin subunits that should allow the visualization of laminin-matrix deposition and assembly by living cells.
Ultrawide‐bandgap (UWBG) semiconductors, with bandgaps significantly wider than the 3.4 eV of GaN, represent an exciting and challenging new area of research in semiconductor materials, physics, ...devices, and applications. Because many figures‐of‐merit for device performance scale nonlinearly with bandgap, these semiconductors have long been known to have compelling potential advantages over their narrower‐bandgap cousins in high‐power and RF electronics, as well as in deep‐UV optoelectronics, quantum information, and extreme‐environment applications. Only recently, however, have the UWBG semiconductor materials, such as high Al‐content AlGaN, diamond and Ga2O3, advanced in maturity to the point where realizing some of their tantalizing advantages is a relatively near‐term possibility. In this article, the materials, physics, device and application research opportunities and challenges for advancing their state of the art are surveyed.
Ultrawide‐bandgap (UWBG) semiconductors, with bandgaps significantly wider than the 3.4 eV of GaN, represent an exciting and challenging new area of research in semiconductor materials, physics, devices and applications. This article surveys and presents an enumerated list of the materials, physics, device and associated application research opportunities and challenges important for advancing the state of their science and technology.
ABSTRACT
Scaling laws of dust, H i gas, and metal mass with stellar mass, specific star formation rate, and metallicity are crucial to our understanding of the build-up of galaxies through their ...enrichment with metals and dust. In this work, we analyse how the dust and metal content varies with specific gas mass (MH i/M⋆) across a diverse sample of 423 nearby galaxies. The observed trends are interpreted with a set of Dust and Element evolUtion modelS (DEUS) – including stellar dust production, grain growth, and dust destruction – within a Bayesian framework to enable a rigorous search of the multidimensional parameter space. We find that these scaling laws for galaxies with −1.0 ≲ log MH i/M⋆ ≲ 0 can be reproduced using closed-box models with high fractions (37–89 ${{\ \rm per\ cent}}$) of supernova dust surviving a reverse shock, relatively low grain growth efficiencies (ϵ = 30–40), and long dust lifetimes (1–2 Gyr). The models have present-day dust masses with similar contributions from stellar sources (50–80 ${{\ \rm per\ cent}}$) and grain growth (20–50 ${{\ \rm per\ cent}}$). Over the entire lifetime of these galaxies, the contribution from stardust (>90 ${{\ \rm per\ cent}}$) outweighs the fraction of dust grown in the interstellar medium (<10 ${{\ \rm per\ cent}}$). Our results provide an alternative for the chemical evolution models that require extremely low supernova dust production efficiencies and short grain growth time-scales to reproduce local scaling laws, and could help solving the conundrum on whether or not grains can grow efficiently in the interstellar medium.
Potato virus Y (PVY) strain groups are based on host response and resistance gene interactions. The strain groups PVYO, PVYC and PVYN are well established for the isolates infecting potato in the ...field. A switch in the emphasis from host response to nucleotide sequence differences in the virus genomes, detection of isolates recombining sequences of different strains, and the need to recognize isolates that cause necrotic symptoms in potato tubers have led to the assignment of new acronyms, especially to isolates of the PVYN strain group. This discussion paper proposes that any newly found isolates should be described within the context of the original strain groups based on the original methods of distinguishing strains (i.e., tobacco and potato assays involving use of 'differential' potato cultivars). Additionally, sequence characterization of the complete genomes of isolates is highly recommended. However, it is acceptable to amend the names of PVY isolates with additional, specific codes to show that the isolate differs at the molecular, serological or phenotypic level from the typical strains within a strain group. The new isolates should preferably not be named using geographical, cultivar, or place-association designations. Since many new variants of PVY are being discovered, any new static classification system will be meaningless for the time being. A more systematic investigation and characterization of PVY from potato at the biological and molecular levels should eventually result in a biologically meaningful genetic strain concept.
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