Optical recording from respiratory pattern generator of foetal mouse brainstem reveals a distributed network

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Neuroscience 137 (2006): 1221-1227, doi:10.1016/j.neuroscience.2005.10.053.Unfailing respiration depends on neural mechanisms already present in mammals before birth. Experiments were made to determine how inspiratory and expiratory neurons are grouped in the brainstem of fetal mice. A further aim was to assess whether rhythmicity arises from a single pacemaker or is generated by multiple sites in the brainstem. To measure neuronal firing, a fluorescent calcium indicator dye was applied to embryonic central nervous systems isolated from mice. While respiratory commands were monitored electrically from third to fifth cervical ventral roots, activity was measured optically over areas containing groups of respiratory neurones, or single neurones, along the medulla from the facial nucleus to the pre-Bötzinger complex. Large optical signals allowed recordings to be made during individual respiratory cycles. Inspiratory and expiratory neurones were intermingled. A novel finding was that bursts of activity arose in a discrete area intermittently, occurring during some breaths, but failing in others. Raised CO2 partial pressure or lowered pH increased the frequency of respiration; neurons then fired reliably with every cycle. Movies of activity revealed patterns of activation of inspiratory and expiratory neurones during successive respiratory cycles; there was no evidence for waves spreading systematically from region to region. Our results suggest that firing of neurons in immature respiratory circuits is a stochastic process, and that the rhythm does not depend on a single pacemaker. Respiratory circuits in fetal mouse brainstem appear to possess a high safety factor for generating rhythmicity, which may or may not persist as development proceeds.Supported by grants from FONDECYT #1010242 and #7010242 to J.E., NIH DC05259 to L.C., the state of FL to K.M., and an Evelyn and Melvin Spiegel Foundation Award for a summer research fellowship at the MBL to J.E

Multi-phase High-Velocity Clouds toward HE 0226-4110 and PG 0953+414

We study the physical conditions, elemental abundances, and kinematics of the high-velocity clouds (HVCs) along the sight lines toward active galaxies HE0226-4110 and PG0953+414 using Hubble Space Telescope Imaging Spectrograph and Far Ultraviolet Spectroscopic Explorer data. Our observations reveal multiple components of HVC absorption in lines of HI, CII, CIII, CIV, OVI, SiII, SiIII, and SiIV in both directions. We investigate whether photoionization by the extragalactic background radiation or by escaping Milky Way radiation can explain the observed ionization pattern. We find that photoionization is a good explanation for the CII, CIII, SiII, and SiIII features, but not for the OVI or CIV associated with the HVCs, suggesting that two principal phases exist: a warm (T~10^4K), photoionized phase and a hotter (T=1-3x10^5K), collisionally-ionized phase. The warm HVCs toward HE0226-4110 have high levels of ionization (97-99%), and metallicities ([Z/H] between -0.9 and -0.4) close to those in the Magellanic Stream, which lies eleven degrees away on the sky at similar velocities. These HVCs have thermal pressures that would place them close to equilibrium in a fully ionized 10^6 K Galactic corona with n_H=4-9x10^{-5}cm^{-3} at 50 kpc. A mini-survey of the hot, collisionally ionized HVC components seen here and in five other sight lines finds that in 11/12 cases, the high ions have kinematics and ionic ratios that are consistent with an origin in conductive interfaces. However, the broad absorption wing on the OVI profile toward PG0953+414 is not completely explained by the interface scenario, and may be tracing the outflow of hot gas into the Milky Way halo as part of a Galactic fountain or wind.Comment: 27 pages, 12 figures (9 in color), accepted for publication in Ap

Control of tumor size and disease activity during cotreatment with octreotide and the growth hormone receptor antagonist pegvisomant in an acromegalic patient

We describe the case of an acromegalic subject, who was the first patient ever treated with the GH receptor antagonist pegvisomant. Furthermore, in this particular patient, progression in tumor size was encountered during treatment with pegvisomant. The patient described did benefit from cotreatment with pegvisomant and octreotide, including decreased GH levels, normalization of serum insulin-like growth factor I concentrations, and improvement of visual field defects

Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease:A Population-Based Cohort Study

Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self-reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self-reported alcohol consumption and EtG with CVD and all-cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study cohort, EtG was measured in 24-hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all-cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self-reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow-up times differed for CVD (8 years; 385 CVD events) and all-cause mortality (14 years; 724 deaths). For both self-reported alcohol consumption and EtG, nonsignificant trends were found toward J-shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1-4 units/month, 1.42; 95% CI, 1.02-1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1-4 units/month, 1.11; 95% CI, 0.68-1.84). Neither self-report nor EtG was associated with all-cause mortality. Conclusions Comparable associations with CVD events and all-cause mortality were found for self-report and EtG. This argues for the validity of self-reported alcohol consumption in epidemiologic research

The Lantern Vol. 6, No. 1, December 1937

• After Thinking Things Over • Ho! Ho! The Mistletoe! • Unrealized Dreams • Two Preeminent Victorians • The Thing • Progression • It Wasn\u27t in the Lines • He Was the Most Perfect Man • College (C)lasses • Robins and Roses • The Commuter • When the Rose is Dead • Truth in Print • Alias Mike Romanoff • Winslow Homer • When I Was Young • Maurice Evans, a Great Shakespearean • Among Our Contributors • Of Manx and Man • A Sanguinary Pirate • Conversation Has an Adventure • Ursinus\u27 Neediest Casehttps://digitalcommons.ursinus.edu/lantern/1016/thumbnail.jp

Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis.

Crohn disease (CD) and ulcerative colitis (UC) are increasingly common, chronic forms of inflammatory bowel disease. The behavior of these diseases varies unpredictably among patients. Identification of reliable prognostic biomarkers would enable treatment to be personalized so that patients destined to experience aggressive disease could receive appropriately potent therapies from diagnosis, while those who will experience more indolent disease are not exposed to the risks and side effects of unnecessary immunosuppression. Using transcriptional profiling of circulating T cells isolated from patients with CD and UC, we identified analogous CD8+ T cell transcriptional signatures that divided patients into 2 otherwise indistinguishable subgroups. In both UC and CD, patients in these subgroups subsequently experienced very different disease courses. A substantially higher incidence of frequently relapsing disease was experienced by those patients in the subgroup defined by elevated expression of genes involved in antigen-dependent T cell responses, including signaling initiated by both IL-7 and TCR ligation - pathways previously associated with prognosis in unrelated autoimmune diseases. No equivalent correlation was observed with CD4+ T cell gene expression. This suggests that the course of otherwise distinct autoimmune and inflammatory conditions may be influenced by common pathways and identifies what we believe to be the first biomarker that can predict prognosis in both UC and CD from diagnosis, a major step toward personalized therapy

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

Severe 2010 Cold-Water Event Caused Unprecedented Mortality to Corals of the Florida Reef Tract and Reversed Previous Survivorship Patterns

Background Coral reefs are facing increasing pressure from natural and anthropogenic stressors that have already caused significant worldwide declines. In January 2010, coral reefs of Florida, United States, were impacted by an extreme cold-water anomaly that exposed corals to temperatures well below their reported thresholds (16°C), causing rapid coral mortality unprecedented in spatial extent and severity. Methodology/Principal Findings Reef surveys were conducted from Martin County to the Lower Florida Keys within weeks of the anomaly. The impacts recorded were catastrophic and exceeded those of any previous disturbances in the region. Coral mortality patterns were directly correlated to in-situ and satellite-derived cold-temperature metrics. These impacts rival, in spatial extent and intensity, the impacts of the well-publicized warm-water bleaching events around the globe. The mean percent coral mortality recorded for all species and subregions was 11.5% in the 2010 winter, compared to 0.5% recorded in the previous five summers, including years like 2005 where warm-water bleaching was prevalent. Highest mean mortality (15%–39%) was documented for inshore habitats where temperatures were \u3c11°C for prolonged periods. Increases in mortality from previous years were significant for 21 of 25 coral species, and were 1–2 orders of magnitude higher for most species. Conclusions/Significance The cold-water anomaly of January 2010 caused the worst coral mortality on record for the Florida Reef Tract, highlighting the potential catastrophic impacts that unusual but extreme climatic events can have on the persistence of coral reefs. Moreover, habitats and species most severely affected were those found in high-coral cover, inshore, shallow reef habitats previously considered the “oases” of the region, having escaped declining patterns observed for more offshore habitats. Thus, the 2010 cold-water anomaly not only caused widespread coral mortality but also reversed prior resistance and resilience patterns that will take decades to recover

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system’s response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform