715 research outputs found
Mortality of federally endangered fishes induced by artificial breaching of the Santa Clara River lagoon, Ventura County, southern California
Fishes of southern California coastal streams and associated coastal lagoons live with a Mediterranean-style hydrological cycle. Winter rains open the lagoons to the ocean; subsequent dry season low flows and changes in sandy beach dynamics closes them for most of the year. Artificial breaching of barrier sand berms can disrupt fish populations and cause mortality. Such breaches have been rarely observed and then only after some time has passed. An artificial breaching at the mouth of the Santa Clara River, Ventura County, CA coincided with an extreme low tide on 17 September 2010. We observed the mortality of thousands of both native and non-native fishes and invasive frogs; including at least thousands of the federally endangered Tidewater Goby (Eucyclogobius newberryi) and seven smolts of the federally endangered southern Steelhead (Oncorhynchus mykiss). Despite the many anthropogenic, faunal, and non-faunally related reasons for breaching, our observations confirm such actions can be detrimental to conservation and recovery of threatened and endangered species as well as to other fauna and flora dependent on such habitats
Expansion of the non-native Mississippi Silverside, Menidia audens (Pisces, Atherinopsidae), into fresh and marine waters of coastal southern California
Abstract--Mississippi Silversides, Menidia audens, were first recorded in southern California reservoirs and nearby outflows in the late 1980s and early 1990s. In 1997-2000 they were taken in King Harbor, Redondo Beach,and in 2000 in the Santa Ana River. By 2005-2006 they were found in several other coastal drainages from the San Gabriel River in Orange and Los Angeles counties northward to Arroyo Burro, Santa Barbara County. Initial invasion was via the California Aqueduct in the late 1980s and early 1990s and more recently dispersal has taken place along the southern California coast. The records from King Harbor occurred for a relatively short period, mid-1997-mid-2000 (mostly 1997 and 1998) before they were established in coastal drainages. Their impact on native species is not known but on some occasions Mississippi Silversides have outnumbered native Topsmelt, Atherinops affinis, in small coastal lagoons estuaries. Mississippi Silversides are known to prey on eggs and larvae of other fishes and could be increasing predation on small native animals as well as serving as prey for larger piscivores like steelhead and terns.
Ultraviolet Signposts of Resonant Dynamics in the Starburst-Ringed Sab Galaxy, M94 (NGC 4736)
M94 (NGC 4736) is investigated using images from the Ultraviolet Imaging
Telescope (FUV-band), Hubble Space Telescope (NUV-band), Kitt Peak 0.9-m
telescope (H-alpha, R, and I bands), and Palomar 5-m telescope (B-band), along
with spectra from the International Ultraviolet Explorer and Lick 1-m
telescopes. The wide-field UIT image shows FUV emission from (a) an elongated
nucleus, (b) a diffuse inner disk, where H-alpha is observed in absorption, (c)
a bright inner ring of H II regions at the perimeter of the inner disk (R = 48
arcsec. = 1.1 kpc), and (d) two 500-pc size knots of hot stars exterior to the
ring on diametrically opposite sides of the nucleus (R= 130 arcsec. = 2.9 kpc).
The HST/FOC image resolves the NUV emission from the nuclear region into a
bright core and a faint 20 arcsec. long ``mini-bar'' at a position angle of 30
deg. Optical and IUE spectroscopy of the nucleus and diffuse inner disk
indicates an approximately 10^7 or 10^8 yr-old stellar population from
low-level starbirth activity blended with some LINER activity. Analysis of the
H-alpha, FUV, NUV, B, R, and I-band emission along with other observed tracers
of stars and gas in M94 indicates that most of the star formation is being
orchestrated via ring-bar dynamics involving the nuclear mini-bar, inner ring,
oval disk, and outer ring. The inner starburst ring and bi-symmetric knots at
intermediate radius, in particular, argue for bar-mediated resonances as the
primary drivers of evolution in M94 at the present epoch. Similar processes may
be governing the evolution of the ``core-dominated'' galaxies that have been
observed at high redshift. The gravitationally-lensed ``Pretzel Galaxy''
(0024+1654) at a redshift of approximately 1.5 provides an important precedent
in this regard.Comment: revised figure 1 (corrected coordinate labels on declination axis);
19 pages of text + 19 figures (jpg files); accepted for publication in A
Long-term qualitative changes in fish populations and aquatic habitat in San Mateo Creek Lagoon, northern San Diego County, southern California, USA.
Observations beginning in 1974 and later surveys of increasing intensity with small seines, traps, and dipnets (1991 to mid-2008) documented patterns of abundance, colonization, and extirpation of 15 species of native and non-native fishes as well as crayfishes, and amphibians in the lagoon at the mouth of San Mateo Creek, northern San Diego County, California. Fish populations varied with Mediterranean climate patterns of stream flow and breaching of the lagoon to the ocean through the barrier sand berm. Two near-record rainfall seasons occurred during this period; the 1997-1998 El Niño due to southern storms and the 2004-2005 winter wet season of more usual storms from the north and northwest. The lagoon stabilized as fresh to brackish in the dry season and for multiple years during successive dry winters. Closed conditions benefitted the native, federally endangered Southern Tidewater Goby, Eucyclogobius n. sp., but were unsuitable for other native estuarine species more common in wetter years. Wet year flows also brought down non-native freshwater species to the lagoon; some thrived and increased predation pressure on the tidewater goby. Historically these exotics were absent and two additional native species were present in the lagoon, Partially Armored Threespine Stickleback, Gasterosteus aculeatus, and the now federally endangered Southern Steelhead, Oncorhynchus mykiss. Restoring and maintaining a full suite of native species will require a combination of 1) habitat maintenance, 2) control or management of non-native species, and 3) reintroduction of some native fishes and amphibians to restore the faunal communities of remaining small coastal estuarine systems
Backbone and side chain NMR assignments for the intrinsically disordered cytoplasmic domain of human neuroligin-3
Neuroligins act as heterophilic adhesion molecules at neuronal synapses. Their cytoplasmic domains interact with synaptic scaffolding proteins, and have been shown to be intrinsically disordered. Here we report the backbone and side chain 1H, 13C and 15N resonance assignments for the cytoplasmic domain of human neuroligin 3
TGF-β-Mediated Sustained ERK1/2 Activity Promotes the Inhibition of Intracellular Growth of Mycobacterium avium in Epithelioid Cells Surrogates
Transforming growth factor beta (TGF-β) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-β production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine peritoneal macrophages through a process of differentiation induced by IL-4 overlap several features of epithelioid cells found in granulomas. In contrast to undifferentiated macrophages, ECs produce larger amounts of TGF-β and inhibit the intracellular growth of M. avium. Here we asked whether the levels of TGF-β produced by ECs are sufficient to induce a self-sustaining autocrine TGF-β signaling controlling mycobacterial replication in infected-cells. We showed that while exogenous addition of increased concentration of TGF-β to infected-macrophages counteracted M. avium replication, pharmacological blockage of TGF-β receptor kinase activity with SB-431542 augmented bacterial load in infected-ECs. Moreover, the levels of TGF-β produced by ECs correlated with high and sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126 increased M. avium replication in infected-cells, suggesting that modulation of intracellular bacterial growth is dependent on the activation of ERK1/2. Interestingly, blockage of TGF-β receptor kinase activity with SB-431542 in infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden and these effects were followed by a severe decrease in TGF-β production. In summary, our findings indicate that the amplitude of TGF-β signaling coordinates the strength and duration of ERK1/2 activity that is determinant for the control of intracellular mycobacterial growth
Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial
Background:
Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB.
Methods:
We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921).
Findings:
Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir.
Interpretation:
Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB
Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires
The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of , and is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 0.02 \mbox{fb}^{-1}. The bosons are reconstructed in the decays , where denotes muon or electron, while the and quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions
Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial
BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir
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