A Dictyostelium chalone uses G proteins to regulate proliferation

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in <it>Dictyostelium</it>. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation.</p> <p>Results</p> <p>We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of <it>galpha8^-</it>, <it>galpha9^-</it>and <it>gbeta^-</it>cells are only weakly inhibited by recombinant AprA (rAprA). Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus), whereas Galpha9 inhibits both proliferation and growth. <it>galpha8^-</it>cells show normal cell-surface binding of rAprA, whereas <it>galpha9^-</it>and <it>gbeta^-</it>cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [³H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [³H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like <it>aprA^-</it>cells, <it>galpha8^-</it>cells have reduced spore viability.</p> <p>Conclusion</p> <p>This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in <it>Dictyostelium</it>, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.</p

Clinical Profile and Outcome of Bronchiolitis in Age Group of 1 – 24 Months

INTRODUCTION: Bronchiolitis remains one of the greatest clinical challenges in pediatric care. Bronchiolitis is a disease of lower respiratory tract that occurs in young children (below 2yrs) and caused by infection with seasonal virus such as RSV, influenza, Adenovirus, influenza and etc. It is a leading cause for the hospitalization of young children, associated with high degree of morbidity but low mortality (<1%). About 20% of infants in the United States get bronchiolitis each year and 2-3% of them require hospitalization. Children younger than one year of age are almost twice as likely to develop bronchiolitis. Currently there is no enough data to determine bronchiolitis rate in the developing and underdeveloped countries. Definition of bronchiolitis varies between the published studies. As per AAP guideline1 defined bronchiolitis as “a constellation of clinical symptoms and signs including upper respiratory prodrome followed by increased respiratory effort and wheezing in children less the two years of age. AIM OF THE STUDY: 1. To study the clinical profile and outcome (hospital stay) of bronchiolitis in age group of 1 – 24 months. 2. To analyze the identifiable risk factors for severity of bronchiolitis. DISCUSSION: Joseph L Mathew et al67, he mentioned that bronchiolitis is regarded as the most common LRTI among infants in developed countries. In our country too, it is a significant problem judging by the frequency of wheezing episode among young infants. Age distribution of bronchiolitis In our study, 58.6% were 1 -6mon age groups, 29.7% were 7– 12mon age groups, nearly 88.3% (196) were belonged to 1 – 12mon age groups which was similar to studies done by Caroline Breese Hall et al8 and Uyan et al26, in their studies 85% of children belonged to less than 12months. One study from U. K.68 63.6% was less than 6 months, 92.8% were less than 12 months, and this study was on populations under 2 years of age. In our study, 11.7% of children were 12 – 24 months of age which was similar to study from Greece69, found that only 10 % of study population were above 12 months of age. P. Flores et al63, 10.6% were belonged to 12 – 24 months of age. In our study, mean age was 6.4 months. In Uyan et al26, mean age was 6.9 months which was similar to our study. Other studies by Arif A et al27 and Iqbal et al25 reported the mean age was 5.43 months and 11.5 months respectively. A.G. Constantopoulos et al69, mean age was 5. 98 months. R.Y.T. Sungi et al6 was reported the mean age was 5 months. These findings are explained that bronchiolitis was most commonly presented by 5 to 7 months of age groups. CONCLUSION: In our study, we concluded that bronchiolitis occurred more commonly in 1-12months of age group with male predominance and most cases occurred in the winter and early spring. Mild and moderate severity was the common presentation in our study. 1-6months age group presented with severe form of bronchiolitis. Irritable cry, poor feeding and aspiration while feeding were more common presentation for the age group of 1-12months and these symptoms were significantly predicting the severity. Children with LBW, not exclusively breast feed, bottle feed, exposed to passive smoking and indoor allergens (wood burning stoves and mosquito repellents), children residing in joint family, increasing birth order and low Socio Economic Status were significantly associated with severity of the bronchiolitis. Sex and parental asthma were not significantly predicting the severity of the bronchiolitis

Dictyostelium cells bind a secreted autocrine factor that represses cell proliferation

<p>Abstract</p> <p>Background</p> <p><it>Dictyostelium </it>cells secrete the proteins AprA and CfaD. Cells lacking either AprA or CfaD proliferate faster than wild type, while AprA or CfaD overexpressor cells proliferate slowly, indicating that AprA and CfaD are autocrine factors that repress proliferation. CfaD interacts with AprA and requires the presence of AprA to slow proliferation. To determine if CfaD is necessary for the ability of AprA to slow proliferation, whether AprA binds to cells, and if so whether the binding requires the presence of CfaD, we examined the binding and effect on proliferation of recombinant AprA.</p> <p>Results</p> <p>We find that the extracellular accumulation of AprA increases with cell density and reaches a concentration of 0.3 μg/ml near a stationary cell density. When added to wild-type or <it>aprA</it>^-cells, recombinant AprA (rAprA) significantly slows proliferation at 0.1 μg/ml and higher concentrations. From 4 to 64 μg/ml, the effect of rAprA is at a plateau, slowing but not stopping proliferation. The proliferation-inhibiting activity of rAprA is roughly the same as that of native AprA in conditioned growth medium. Proliferating <it>aprA</it>^-cells show saturable binding of rAprA to 92,000 ± 11,000 cell-surface receptors with a <it>K</it>_{<it>D </it>}of 0.03 ± 0.02 μg/ml. There appears to be one class of binding site, and no apparent cooperativity. Native AprA inhibits the binding of rAprA to <it>aprA</it>^-cells with a <it>K</it>_{<it>i </it>}of 0.03 μg/ml, suggesting that the binding kinetics of rAprA are similar to those of native AprA. The proliferation of cells lacking CrlA, a cAMP receptor-like protein, or cells lacking CfaD are not affected by rAprA. Surprisingly, both cell types still bind rAprA.</p> <p>Conclusion</p> <p>Together, the data suggest that AprA functions as an autocrine proliferation-inhibiting factor by binding to cell surface receptors. Although AprA requires CfaD for activity, it does not require CfaD to bind to cells, suggesting the possibility that cells have an AprA receptor and a CfaD receptor, and activation of both receptors is required to slow proliferation. We previously found that <it>crlA</it>^-cells are sensitive to CfaD. Combined with the results presented here, this suggests that CrlA is not the AprA or CfaD receptor, and may be the receptor for an unknown third factor that is required for AprA and CfaD activity.</p

Genetic monitoring detects an overlooked cryptic species and reveals the diversity and distribution of three invasive Rattus congeners in South Africa

Background: South Africa's long and extensive trade activity has ensured ample opportunities for exotic species introduction. Whereas the rich biodiversity of endemic southern African fauna has been the focus of many studies, invasive vertebrates are generally overlooked despite potential impacts on biodiversity, health and agriculture. Genetic monitoring of commensal rodents in South Africa which uncovered the presence of Rattus tanezumi, a South-East Asian endemic not previously known to occur in Africa, provided the impetus for expanded studies on all invasive Rattus species present. Results: To this end, intensified sampling at 28 South African localities and at one site in Swaziland, identified 149 Rattus specimens. Cytochrome b gene sequencing revealed the presence of two R. tanezumi, seven R. rattus and five R. norvegicus haplotypes in south Africa. Phylogenetic results were consistent with a single, recent R. tanezumi introduction and indicated that R. norvegicus and R. rattus probably became established following at least two and three independent introductions, respectively. Intra- and inter-specific diversity was highest in informal human settlements, with all three species occurring at a single metropolitan township site. Rattus norvegicus and R. rattus each occurred sympatrically with R. tanezumi at one and five sites, respectively. Karyotyping of selected R. rattus and R. tanezumi individuals identified diploid numbers consistent with those reported previously for these cryptic species. Ordination of bioclimatic variables and MaxEnt ecological niche modelling confirmed that the bioclimatic niche occupied by R. tanezumi in south Africa was distinct from that occupied in its naturalised range in south-east Asia suggesting that factors other than climate may influence the distribution of this species. Conclusions: This study has highlighted the value of genetic typing for detecting cryptic invasive species, providing historical insights into introductions and for directing future sampling. The apparent ease with which a cryptic species can become established signals the need for broader implementation of genetic monitoring programmes. In addition to providing baseline data and potentially identifying high-risk introduction routes, the predictive power of ecological niche modelling is enhanced when species records are genetically verified

First measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary–Black-hole Merger GW170814

International audienceWe present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

Erratum: “Searches for Gravitational Waves from Known Pulsars at Two Harmonics in 2015–2017 LIGO Data” (2019, ApJ, 879, 10)

Due to an error at the publisher, in the published article the number of pulsars presented in the paper is incorrect in multiple places throughout the text. Specifically, "222" pulsars should be "221." Additionally, the number of pulsars for which we have EM observations that fully overlap with O1 and O2 changes from "168" to "167." Elsewhere, in the machine-readable table of Table 1 and in Table 2, the row corresponding to pulsar J0952-0607 should be excised as well. Finally, in the caption for Table 2 the number of pulsars changes from "188" to "187.

Searches for gravitational waves from known pulsars at two harmonics in 2015-2017 LIGO data

International audienceWe present a search for gravitational waves from 222 pulsars with rotation frequencies ≳10 Hz. We use advanced LIGO data from its first and second observing runs spanning 2015–2017, which provides the highest-sensitivity gravitational-wave data so far obtained. In this search we target emission from both the l = m = 2 mass quadrupole mode, with a frequency at twice that of the pulsar’s rotation, and the l = 2, m = 1 mode, with a frequency at the pulsar rotation frequency. The search finds no evidence for gravitational-wave emission from any pulsar at either frequency. For the l = m = 2 mode search, we provide updated upper limits on the gravitational-wave amplitude, mass quadrupole moment, and fiducial ellipticity for 167 pulsars, and the first such limits for a further 55. For 20 young pulsars these results give limits that are below those inferred from the pulsars’ spin-down. For the Crab and Vela pulsars our results constrain gravitational-wave emission to account for less than 0.017% and 0.18% of the spin-down luminosity, respectively. For the recycled millisecond pulsar J0711−6830 our limits are only a factor of 1.3 above the spin-down limit, assuming the canonical value of 1038 kg m2 for the star’s moment of inertia, and imply a gravitational-wave-derived upper limit on the star’s ellipticity of 1.2 × 10−8. We also place new limits on the emission amplitude at the rotation frequency of the pulsars

GWTC-1: A Gravitational-Wave Transient Catalog of Compact Binary Mergers Observed by LIGO and Virgo during the First and Second Observing Runs

We present the results from three gravitational-wave searches for coalescing compact binaries with component masses above 1  M⊙ during the first and second observing runs of the advanced gravitational-wave detector network. During the first observing run (O1), from September 12, 2015 to January 19, 2016, gravitational waves from three binary black hole mergers were detected. The second observing run (O2), which ran from November 30, 2016 to August 25, 2017, saw the first detection of gravitational waves from a binary neutron star inspiral, in addition to the observation of gravitational waves from a total of seven binary black hole mergers, four of which we report here for the first time: GW170729, GW170809, GW170818, and GW170823. For all significant gravitational-wave events, we provide estimates of the source properties. The detected binary black holes have total masses between 18.6−0.7+3.2  M⊙ and 84.4−11.1+15.8  M⊙ and range in distance between 320−110+120 and 2840−1360+1400  Mpc. No neutron star-black hole mergers were detected. In addition to highly significant gravitational-wave events, we also provide a list of marginal event candidates with an estimated false-alarm rate less than 1 per 30 days. From these results over the first two observing runs, which include approximately one gravitational-wave detection per 15 days of data searched, we infer merger rates at the 90% confidence intervals of 110−3840  Gpc−3 y−1 for binary neutron stars and 9.7−101  Gpc−3 y−1 for binary black holes assuming fixed population distributions and determine a neutron star-black hole merger rate 90% upper limit of 610  Gpc−3 y−1