A sensitivity of the circadian clock to light/dark cycles ensures that biological rhythms maintain optimal phase relationships with the external day. In animals, the circadian clock neuron network ...(CCNN) driving sleep/activity rhythms receives light input from multiple photoreceptors, but how these photoreceptors modulate CCNN components is not well understood. Here we show that the Hofbauer-Buchner eyelets differentially modulate two classes of ventral lateral neurons (LNvs) within the Drosophila CCNN. The eyelets antagonize Cryptochrome (CRY)- and compound-eye-based photoreception in the large LNvs while synergizing CRY-mediated photoreception in the small LNvs. Furthermore, we show that the large LNvs interact with subsets of "evening cells" to adjust the timing of the evening peak of activity in a day length-dependent manner. Our work identifies a peptidergic connection between the large LNvs and a group of evening cells that is critical for the seasonal adjustment of circadian rhythms.
In animals, circadian clocks have evolved to orchestrate the timing of behavior and metabolism. Consistent timing requires the entrainment these clocks to the solar day, a process that is critical for an organism's health. Light cycles are the most important external cue for the entrainment of circadian clocks, and the circadian system uses multiple photoreceptors to link timekeeping to the light/dark cycle. How light information from these photorecptors is integrated into the circadian clock neuron network to support entrainment is not understood. Our results establish that input from the HB eyelets differentially impacts the physiology of neuronal subgroups. This input pathway, together with input from the compound eyes, precisely times the activity of flies under long summer days. Our results provide a mechanistic model of light transduction and integration into the circadian system, identifying new and unexpected network motifs within the circadian clock neuron network.
Abstract
Extreme emission-line galaxies (EELGs) at redshift
z
= 1−2 provide a unique view of metal-poor, starburst sources that are the likely drivers of the cosmic reionization at
z
≥ 6. However, ...the molecular gas reservoirs of EELGs—the fuel for their intense star formation—remain beyond the reach of current facilities. We present ALMA C
ii
and PdBI CO(2–1) observations of the
z
= 1.8, strongly lensed EELG SL2S 0217, a bright Ly
α
emitter with a metallicity 0.05
Z
⊙
. We obtain a tentative (∼3
σ
–4
σ
) detection of the C
ii
line and set an upper limit on the C
ii
/SFR (star-forming rate) ratio of ≤1 × 10
6
L
⊙
/(
M
⊙
yr
−1
), based on the synthesized images and visibility-plane analysis. The CO(2–1) emission is not detected. Photoionization modeling indicates that up to 80% of the C
ii
emission originates from neutral or molecular gas, although we cannot rule out that the gas is fully ionized. The very faint C
ii
emission is in line with both nearby metal-poor dwarfs and high-redshift Ly
α
emitters, and predictions from hydrodynamical simulations. However, the C
ii
line is 30× fainter than predicted by the De Looze et al. C
ii
–SFR relation for local dwarfs, illustrating the danger of extrapolating locally calibrated relations to high-redshift, metal-poor galaxies.
We present a high-resolution radio survey of the Sloan Digital Sky Survey (SDSS) Southern Equatorial Stripe, a.k.a. Stripe 82. This 1.4 GHz survey was conducted with the Very Large Array primarily in ...the A-configuration, with supplemental B-configuration data to increase sensitivity to extended structure. The survey has an angular resolution of 18 and achieves a median rms noise of 52 mu Jy beam super(-1) over 92 deg super(2). This is the deepest 1.4 GHz survey to achieve this large of an area, filling a gap in the phase space between small, deep and large, shallow surveys. It also serves as a pilot project for a larger high-resolution survey with the Expanded Very Large Array. We discuss the technical design of the survey and details of the observations, and we outline our method for data reduction. We present a catalog of 17,969 isolated radio components, for an overall source density of similar to 195 sources deg-2. The astrometric accuracy of the data is excellent, with an internal check utilizing multiply observed sources yielding an rms scatter of 019 in both right ascension and declination. A comparison to the SDSS DR7 Quasar Catalog further confirms that the astrometry is well tied to the optical reference frame, with mean offsets of 002 plus or minus 001 in right ascension, and 001 plus or minus 002 in declination. A check of our photometry reveals a small, negative CLEAN-like bias on the level of 35 mu Jy. We report on the catalog completeness, finding that 97% of FIRST-detected quasars are recovered in the new Stripe 82 radio catalog, while faint, extended sources are more likely to be resolved out by the resolution bias. We conclude with a discussion of the optical counterparts to the catalog sources, including 76 newly detected radio quasars. The full catalog as well as a search page and cutout server are available online at http://third.ucllnl.org/cgi-bin/stripe82cutout.
Prolonged cellular activity may overload cell function, leading to high rates of protein synthesis and accumulation of misfolded or unassembled proteins, which cause endoplasmic reticulum (ER) stress ...and activate the unfolded protein response (UPR) to re-establish normal protein homeostasis. Previous molecular work has demonstrated that sleep deprivation (SD) leads to ER stress in neurons, with a number of ER-specific proteins being upregulated to maintain optimal cellular proteostasis. It is still not clear which cellular processes activated by sleep deprivation lead to ER- stress, but increased cellular metabolism, higher request for protein synthesis, and over production of oxygen radicals have been proposed as potential contributing factors. Here, we investigate the transcriptional and ultrastructural ER and mitochondrial modifications induced by sleep loss.
We used gene expression analysis in mouse forebrains to show that SD was associated with significant transcriptional modifications of genes involved in ER stress but also in ER-mitochondria interaction, calcium homeostasis, and mitochondrial respiratory activity. Using electron microscopy, we also showed that SD was associated with a general increase in the density of ER cisternae in pyramidal neurons of the motor cortex. Moreover, ER cisternae established new contact sites with mitochondria, the so-called mitochondria associated membranes (MAMs), important hubs for molecule shuttling, such as calcium and lipids, and for the modulation of ATP production and redox state. Finally, we demonstrated that Drosophila male mutant flies (elav > linker), in which the number of MAMs had been genetically increased, showed a reduction in the amount and consolidation of sleep without alterations in the homeostatic sleep response to SD.
We provide evidence that sleep loss induces ER stress characterized by increased crosstalk between ER and mitochondria. MAMs formation associated with SD could represent a key phenomenon for the modulation of multiple cellular processes that ensure appropriate responses to increased cell metabolism. In addition, MAMs establishment may play a role in the regulation of sleep under baseline conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Conspicuous coloration displayed by animals that express sexual colour dimorphism is generally explained as an adaptation to sexual selection, yet the interactions and relative effects of selective ...forces influencing colour dimorphism are largely unknown. Qualitatively, colour dimorphism appears more pronounced in marine fishes that live on coral reefs where traits associated with strong sexual selection are purportedly more common. Using phylogenetic comparative analysis, we show that wrasses and parrotfishes exclusive to coral reefs are the most colour dimorphic, but surprisingly, the effect of habitat is not influenced by traits associated with strong sexual selection. Rather, habitat-specific selective forces, including clear water and structural refuge, promote the evolution of pronounced colour dimorphism that manifests colours less likely to be displayed in other habitats. Our results demonstrate that environmental context ultimately determines the evolution of conspicuous coloration in colour-dimorphic labrid fishes, despite other influential selective forces.
The 2017 World Workshop Classification system for periodontal and peri-implant diseases and conditions was developed in order to accommodate advances in knowledge derived from both biological and ...clinical research, that have emerged since the 1999 International Classification of Periodontal Diseases. Importantly, it defines clinical health for the first time, and distinguishes an intact and a reduced periodontium throughout. The term 'aggressive periodontitis' was removed, creating a staging and grading system for periodontitis that is based primarily upon attachment and bone loss and classifies the disease into four stages based on severity (I, II, III or IV) and three grades based on disease susceptibility (A, B or C). The British Society of Periodontology (BSP) convened an implementation group to develop guidance on how the new classification system should be implemented in clinical practice. A particular focus was to describe how the new classification system integrates with established diagnostic parameters and pathways, such as the basic periodontal examination (BPE). This implementation plan focuses on clinical practice; for research, readers are advised to follow the international classification system. In this paper we describe a diagnostic pathway for plaque-induced periodontal diseases that is consistent with established guidance and accommodates the novel 2017 classification system, as recommended by the BSP implementation group. Subsequent case reports will provide examples of the application of this guidance in clinical practice.
ABSTRACT We present an analysis of a deep (1 = 13 Jy) cosmological 1.2 mm continuum map based on ASPECS, the ALMA Spectroscopic Survey in the Hubble Ultra Deep Field. In the 1 arcmin2 covered by ...ASPECS we detect nine sources at significance at 1.2 mm. Our ALMA-selected sample has a median redshift of , with only one galaxy detected at z > 2 within the survey area. This value is significantly lower than that found in millimeter samples selected at a higher flux density cutoff and similar frequencies. Most galaxies have specific star formation rates (SFRs) similar to that of main-sequence galaxies at the same epoch, and we find median values of stellar mass and SFRs of and yr−1, respectively. Using the dust emission as a tracer for the interstellar medium (ISM) mass, we derive depletion times that are typically longer than 300 Myr, and we find molecular gas fractions ranging from ∼0.1 to 1.0. As noted by previous studies, these values are lower than those using CO-based ISM estimates by a factor of ∼2. The 1 mm number counts (corrected for fidelity and completeness) are in agreement with previous studies that were typically restricted to brighter sources. With our individual detections only, we recover 55% 4% of the extragalactic background light (EBL) at 1.2 mm measured by the Planck satellite, and we recover 80% 7% of this EBL if we include the bright end of the number counts and additional detections from stacking. The stacked contribution is dominated by galaxies at , with stellar masses of (1-3) × 1010 M . For the first time, we are able to characterize the population of galaxies that dominate the EBL at 1.2 mm.
In chronic obstructive pulmonary disease (COPD) apoptotic bronchial epithelial cells are increased, and their phagocytosis by alveolar macrophages (AM) is decreased alongside bacterial phagocytosis. ...Epithelial cellular lipids, including those exposed on uncleared apoptotic bodies, can become oxidized, and may be recognized and presented as non-self by antigen presenting cells. CD1b is a lipid-presenting protein, previously only described in dendritic cells. We investigated whether CD1b is upregulated in COPD AM, and whether lipid oxidation products are found in the airways of cigarette smoke (CS) exposed mice. We also characterise CD1b for the first time in a range of macrophages and assess CD1b expression and phagocytic function in response to oxidised lipid. Bronchoalveolar lavage and exhaled breath condensate were collected from never-smoker, current-smoker, and COPD patients and AM CD1b expression and airway 8-isoprostane levels assessed. Malondialdehyde was measured in CS-exposed mouse airways by confocal/immunofluorescence. Oxidation of lipids produced from CS-exposed 16HBE14o- (HBE) bronchial epithelial cells was assessed by spectrophotometry and changes in lipid classes assessed by mass spectrometry. 16HBE cell toxicity was measured by flow cytometry as was phagocytosis, CD1b expression, HLA class I/II, and mannose receptor (MR) in monocyte derived macrophages (MDM). AM CD1b was significantly increased in COPD smokers (4.5 fold), COPD ex-smokers (4.3 fold), and smokers (3.9 fold), and AM CD1b significantly correlated with disease severity (FEV
) and smoking pack years. Airway 8-isoprostane also increased in smokers and COPD smokers and ex-smokers. Malondialdehyde was significantly increased in the bronchial epithelium of CS-exposed mice (MFI of 18.18 vs 23.50 for control). Oxidised lipid was produced from CS-exposed bronchial epithelial cells (9.8-fold of control) and showed a different overall lipid makeup to that of control total cellular lipid. This oxidised epithelial lipid significantly upregulated MDM CD1b, caused bronchial epithelial cell toxicity, and reduced MDM phagocytic capacity and MR in a dose dependent manner. Increased levels of oxidised lipids in the airways of COPD patients may be responsible for reduced phagocytosis and may become a self-antigen to be presented by CD1b on macrophages to perpetuate disease progression despite smoking cessation.
Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. ...Therefore, tofacitinib effects on synovial pathobiology were investigated.
A randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699).
Tofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p<0.05) and chemokines CCL2, CXCL10 and CXCL13 (p<0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p<0.002). Tofacitinib significantly decreased plasma CXCL10 (p<0.005) at Day 28 compared with placebo.
Tofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response.
NCT00976599.
We present an Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 0 survey of 126 submillimeter sources from the LABOCA ECDFS Submillimeter Survey (LESS). Our 870 mu m survey with ALMA (ALESS) ...has produced maps ~3x deeper and with a beam area ~200x smaller than the original LESS observations, doubling the current number of interferometrically-observed submillimeter sources. The high resolution of these maps allows us to resolve sources that were previously blended and accurately identify the origin of the submillimeter emission. We discuss the creation of the ALESS submillimeter galaxy (SMG) catalog, including the main sample of 99 SMGs and a supplementary sample of 32 SMGs. We find that at least 35% (possibly up to 50%) of the detected LABOCA sources have been resolved into multiple SMGs, and that the average number of SMGs per LESS source increases with LESS flux density. Using the (now precisely known) SMG positions, we empirically test the theoretical expectation for the uncertainty in the single-dish source positions. We also compare our catalog to the previously predicted radio/mid-infrared counterparts, finding that 45% of the ALESS SMGs were missed by this method. Our ~1".6 resolution allows us to measure a size of ~9 kpc x 5 kpc for the rest-frame ~300 mu m emission region in one resolved SMG, implying a star formation rate surface density of 80 M sub(middot in circle) yr super(-1) kpc super(-2), and we constrain the emission regions in the remaining SMGs to be < 10 kpc. As the first statistically reliable survey of SMGs, this will provide the basis for an unbiased multiwavelength study of SMG properties.
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![Ultrafaint [C ii] Emission ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0004-637X/small "Ultrafaint [C ii] Emission in a Redshift = 2 Gravitationally Lensed Metal-poor Dwarf Galaxy")
