The Effelsberg survey of FU Orionis and EX Lupi objects I. -- Host environments of FUors/EXors traced by NH3_3

FU Orionis (FUor) and EX Lupi (EXor) type objects represent two small, but rather spectacular groups of low-mass, young eruptive stars. Outbursts of several magnitudes are observed, attributed to enhanced accretion from the circumstellar disk onto the central protostar. The host molecular environments of FUors/EXors are poorly explored due to the scarcity of systematic molecular line observations. We carried out the first dedicated survey of the molecular environments of a large sample of FUors/EXors, observing a total of 51 sources with the aim of studying the ammonia (NH$_3$) emission in their host environments. We observed the ammonia (J,K)=(1,1), (2,2), and (3,3) inversion transitions using the Effelsberg 100-m radio telescope. We derived H$_2$ column densities and dust temperatures using archival Herschel SPIRE data. We detected the (1,1) transition toward 28 sources and the (2,2) transition toward 12 sources, while the (3,3) transition was detected toward only two sources. We find kinetic temperatures between ~12 K and 21 K, ammonia column densities from $5.2\times10^{13}\,cm^{-2}$ to $3.2\times10^{15}\,cm^{-2}$, and fractional ammonia abundances with respect to H$_{2}$ from $4.7\times10^{-9}$ to $1.5\times10^{-7}$. The results are comparable to those found in infrared dark clouds (IRDCs). Kinetic analysis suggests that most of the eruptive stars in our sample reside in rather quiescent (sonic or transonic) host environments. Our NH$_3$ observations and analysis of the SPIRE dust-based H$_2$ column density maps confirm the presence of dense material toward 7 sources in our sample; additional sources might also harbour dense gas based on their NH$_2$ (2,2) detections, might indicate an earlier phase than originally classified. Based on our results, we suggest observations targeting additional molecular lines would help to refine the evolutionary classification of eruptive stars.Comment: 20 pages, 2 figures, accepted for publication in A&

The Effelsberg survey of FU~Orionis and EX~Lupi objects II. H2O maser observations

Funding: Zs.M.Sz. acknowledges funding from a St Leonards scholarship from the University of St Andrews. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 716155 (SACCRED).Context. FU Orionis (FUor) and EX Lupi (EXor) type objects are two groups of peculiar and rare pre-main sequence low-mass stars that are undergoing powerful accretion outbursts during their early stellar evolution. Although water masers are widespread in star-forming regions and serve as powerful probes of mass accretion and ejection on small scales, little is known about the prevalence of water masers toward FUors and EXors. Aims. We aim to perform the first systematic search for the 22.2 GHz water maser line in FUors and EXors in order to determine its overall incidence in these eruptive variables and to facilitate high angular-resolution follow-up observations. Methods. We used the Effelsberg 100-m radio telescope to observe the H2O (616 – 523) transition at 22.2GHz toward a sample of 51 eruptive young stellar objects. Results. We detected a total of five water masers in our survey; three are associated with eruptive stars, equivalent to a detection rate of ~6% for our sample of eruptive sources. These detections include one EXor, V512 Per (also known as SVS 13 or SVS 13A), and two FUors, Z CMa, and HH 354 IRS. This is the first reported detection of water maser emission towards HH 354 IRS. We also detected water maser emission in our pointing towards the FUor binary RNO 1B/1C, which most likely originates from the nearby deeply embedded source IRAS 00338+6312 (~4″ from RNO 1B/1C). Emission was also detected from H2O(B), (also known as SVS 13C), a Class 0 source ~30″ from the EXor V512 Per. The peak flux density of H2O(B) in our observations, 498.7 Jy, is the highest observed to date, indicating that we have serendipitously detected a water maser flare in this source. In addition to the two non-eruptive Class 0 sources (IRAS 00338+6312 and H2O(B)/SVS 13C), we detected maser emission towards one Class 0/I (HH 354 IRS) and two Class I (V512 Per/SVS 13A and Z CMa) eruptive stars. Conclusions. Despite the low detection rate, we demonstrate the presence of 22.2 GHz water maser emission in both FUor and EXor systems, paving the way to radio interferometric observations to study the environments of these eruptive stars on small scales. Comparisons of our data with historical observations spanning several decades suggest that multiple water maser flares have occurred in both V512 Per and H2O(B).Publisher PDFPeer reviewe

Cyclic AMP-Dependent Protein Kinase A Regulates the Alternative Splicing of CaMKIIδ

Ca2+/calmodulin-dependent protein kinase (CaMK) IIδ is predominantly expressed in the heart. There are three isoforms of CaMKIIδ resulting from the alternative splicing of exons 14, 15, and 16 of its pre-mRNA, which is regulated by the splicing factor SF2/ASF. Inclusion of exons 15 and 16 or of exon 14 generates δA or δB isoform. The exclusion of all three exons gives rise to δC isoform, which is selectively increased in pressure-overload-induced hypertrophy. Overexpression of either δB or δC induces hypertrophy and heart failure, suggesting their specific role in the pathogenesis of hypertrophy and heart failure. It is well known that the β-adrenergic-cyclic AMP-dependent protein kinase A (PKA) pathway is implicated in heart failure. To determine the role of PKA in the alternative splicing of CaMKIIδ, we constructed mini-CaMKIIδ genes and used these genes to investigate the regulation of the alternative splicing of CaMKIIδ by PKA in cultured cells. We found that PKA promoted the exclusion of exons 14, 15, and 16 of CaMKIIδ, resulting in an increase in δC isoform. PKA interacted with and phosphorylated SF2/ASF, and enhanced SF2/ASF's activity to promote the exclusion of exons 14, 15, and 16 of CaMKIIδ, leading to a further increase in the expression of δC isoform. These findings suggest that abnormality in β-adrenergic-PKA signaling may contribute to cardiomyopathy and heart failure through dysregulation in the alternative splicing of CaMKIIδ exons 14, 15, and 16 and up-regulation of CaMKIIδC

Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Aβ42 Uptake and Lysosomal Trafficking

Alzheimer's disease (AD) is characterized by the presence of early intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular amyloid deposition in vulnerable brain regions. It has been hypothesized that endosomal/lysosomal dysfunction might be associated with the pathological accumulation of intracellular Abeta42 in the brain. Our previous findings suggest that the LDL receptor-related protein 1 (LRP1), a major receptor for apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain. However, direct evidence of neuronal endocytosis of Abeta42 through LRP1 is lacking.Here we show that LRP1 endocytic function is required for neuronal Abeta42 uptake. Overexpression of a functional LRP1 minireceptor, mLRP4, increases Abeta42 uptake and accumulation in neuronal lysosomes. Conversely, knockdown of LRP1 expression significantly decreases neuronal Abeta42 uptake. Disruptions of LRP1 endocytic function by either clathrin knockdown or by removal of its cytoplasmic tail decreased both uptake and accumulation of Abeta42 in neurons. Finally, we show that LRP1-mediated neuronal accumulation of Abeta42 is associated with increased cellular toxicity.These results demonstrate that LRP1 endocytic function plays an important role in the uptake and accumulation of Abeta42 in neuronal lysosomes. These findings emphasize the central function of LRP1 in neuronal Abeta metabolism

Vanin-1 Pantetheinase Drives Smooth Muscle Cell Activation in Post-Arterial Injury Neointimal Hyperplasia

The pantetheinase vanin-1 generates cysteamine, which inhibits reduced glutathione (GSH) synthesis. Vanin-1 promotes inflammation and tissue injury partly by inducing oxidative stress, and partly by peroxisome proliferator-activated receptor gamma (PPARγ) expression. Vascular smooth muscle cells (SMCs) contribute to neointimal hyperplasia in response to injury, by multiple mechanisms including modulation of oxidative stress and PPARγ. Therefore, we tested the hypothesis that vanin-1 drives SMC activation and neointimal hyperplasia. We studied reactive oxygen species (ROS) generation and functional responses to platelet-derived growth factor (PDGF) and the pro-oxidant diamide in cultured mouse aortic SMCs, and also assessed neointima formation after carotid artery ligation in vanin-1 deficiency. Vnn1−/− SMCs demonstrated decreased oxidative stress, proliferation, migration, and matrix metalloproteinase 9 (MMP-9) activity in response to PDGF and/or diamide, with the effects on proliferation linked, in these studies, to both increased GSH levels and PPARγ expression. Vnn1−/− mice displayed markedly decreased neointima formation in response to carotid artery ligation, including decreased intima:media ratio and cross-sectional area of the neointima. We conclude that vanin-1, via dual modulation of GSH and PPARγ, critically regulates the activation of cultured SMCs and development of neointimal hyperplasia in response to carotid artery ligation. Vanin-1 is a novel potential therapeutic target for neointimal hyperplasia following revascularization

Review of risk factors for human echinococcosis prevalence on the Qinghai-Tibet Plateau, China: a prospective for control options

Objective: Echinococcosis is a major parasitic zoonosis of public health importance in western China. In 2004, the Chinese Ministry of Health estimated that 380,000 people had the disease in the region. The Qinghai-Tibet Plateau is highly co-endemic with both alveolar echinococcosis (AE) and cystic echinococcosis (CE). In the past years, the Chinese government has been increasing the financial support to control the diseases in this region. Therefore, it is very important to identify the significant risk factors of the diseases by reviewing studies done in the region in the past decade to help policymakers design appropriate control strategies. Review: Selection criteria for which literature to review were firstly defined. Medline, CNKI (China National Knowledge Infrastructure), and Google Scholar were systematically searched for literature published between January 2000 and July 2011. Significant risk factors found by single factor and/or multiple factors analysis were listed, counted, and summarized. Literature was examined to check the comparability of the data; age and sex specific prevalence with same data structures were merged and used for further analysis. A variety of assumed social, economical, behavioral, and ecological risk factors were studied on the Plateau. Those most at risk were Tibetan herdsmen, the old and female in particular. By analyzing merged comparable data, it was found that females had a significant higher prevalence, and a positive linearity relationship existed between echinococcosis prevalence and increasing age. In terms of behavioral risk factors, playing with dogs was mostly correlated with CE and/or AE prevalence. In terms of hygiene, employing ground water as the drinking water source was significantly correlated with CE and AE prevalence. For definitive hosts, dog related factors were most frequently identified with prevalence of CE or/and AE; fox was a potential risk factor for AE prevalence only. Overgrazing and deforestation were significant for AE prevalence only. Conclusion: Tibetan herdsmen communities were at the highest risk of echinococcosis prevalence and should be the focus of echinococcosis control. Deworming both owned and stray dogs should be a major measure for controlling echinococcosis; treatment of wild definitive hosts should also be considered for AE endemic areas. Health education activities should be in concert with the local people's education backgrounds and languages in order to be able to improve behaviors. Further researches are needed to clarify the importance of wild hosts for AE/CE prevalence, the extent and range of the impacts of ecologic changes (overgrazing and deforestation) on the AE prevalence, and risk factors in Tibet

Large-Scale Cortical Functional Organization and Speech Perception across the Lifespan

Aging is accompanied by substantial changes in brain function, including functional reorganization of large-scale brain networks. Such differences in network architecture have been reported both at rest and during cognitive task performance, but an open question is whether these age-related differences show task-dependent effects or represent only task-independent changes attributable to a common factor (i.e., underlying physiological decline). To address this question, we used graph theoretic analysis to construct weighted cortical functional networks from hemodynamic (functional MRI) responses in 12 younger and 12 older adults during a speech perception task performed in both quiet and noisy listening conditions. Functional networks were constructed for each subject and listening condition based on inter-regional correlations of the fMRI signal among 66 cortical regions, and network measures of global and local efficiency were computed. Across listening conditions, older adult networks showed significantly decreased global (but not local) efficiency relative to younger adults after normalizing measures to surrogate random networks. Although listening condition produced no main effects on whole-cortex network organization, a significant age group x listening condition interaction was observed. Additionally, an exploratory analysis of regional effects uncovered age-related declines in both global and local efficiency concentrated exclusively in auditory areas (bilateral superior and middle temporal cortex), further suggestive of specificity to the speech perception tasks. Global efficiency also correlated positively with mean cortical thickness across all subjects, establishing gross cortical atrophy as a task-independent contributor to age-related differences in functional organization. Together, our findings provide evidence of age-related disruptions in cortical functional network organization during speech perception tasks, and suggest that although task-independent effects such as cortical atrophy clearly underlie age-related changes in cortical functional organization, age-related differences also demonstrate sensitivity to task domains

Wnt signaling in triple-negative breast cancer

Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease

Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature

Background The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. Conclusions Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies