1,025 research outputs found
Effectiveness of additional follow-up telephone counseling in a smoking cessation clinic in Beijing and predictors of quitting among Chinese male smokers
published_or_final_versio
Effectiveness of varenicline and counseling for smoking cessation in an observational cohort study in China
published_or_final_versio
Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.
To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome
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Detection of Oxidation Products of 5-Methyl-2′-Deoxycytidine in Arabidopsis DNA
Epigenetic regulations play important roles in plant development and adaptation to environmental stress. Recent studies
from mammalian systems have demonstrated the involvement of ten-eleven translocation (Tet) family of dioxygenases in
the generation of a series of oxidized derivatives of 5-methylcytosine (5-mC) in mammalian DNA. In addition, these oxidized
5-mC nucleobases have important roles in epigenetic remodeling and aberrant levels of 5-hydroxymethyl-29-deoxycytidine
(5-HmdC) were found to be associated with different types of human cancers. However, there is a lack of evidence
supporting the presence of these modified bases in plant DNA. Here we reported the use of a reversed-phase HPLC coupled
with tandem mass spectrometry method and stable isotope-labeled standards for assessing the levels of the oxidized 5-mC
nucleosides along with two other oxidatively induced DNA modifications in genomic DNA of Arabidopsis. These included 5-
HmdC, 5-formyl-29-deoxycytidine (5-FodC), 5-carboxyl-29-deoxycytidine (5-CadC), 5-hydroxymethyl-29-deoxyuridine (5-
HmdU), and the (59S) diastereomer of 8,59-cyclo-29-deoxyguanosine (S-cdG). We found that, in Arabidopsis DNA, the levels
of 5-HmdC, 5-FodC, and 5-CadC are approximately 0.8 modifications per 106 nucleosides, with the frequency of 5-HmdC
(per 5-mdC) being comparable to that of 5-HmdU (per thymidine). The relatively low levels of the 5-mdC oxidation products
suggest that they arise likely from reactive oxygen species present in cells, which is in line with the lack of homologous Tetfamily
dioxygenase enzymes in Arabidopsis
5-Formylcytosine can be a stable DNA modification in mammals.
5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA modification. These results suggest that 5fC has functional roles in DNA that go beyond being a demethylation intermediate.This work was supported by the Cancer Research UK (C14303/A17197, S.B.), The Wellcome Trust (WT099232, S.B.; WT095645/Z/11/Z, W.R.) and the BBSRC (BB/K010867/1, W.R.).This is the accepted manuscript. It is currently embargoed pending publication
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Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study
The blockchain technology promises to transform finance, money and evengovernments. However, analyses of blockchain applicability and robustness typicallyfocus on isolated systems whose actors contribute mainly by running the consensusalgorithm. Here, we highlight the importance of considering trustless platformswithin the broader ecosystem that includes social and communication networks. Asan example, we analyse the flash-crash observed on 21st June 2017 in the Ethereumplatform and show that a major phenomenon of social coordination led to acatastrophic cascade of events across several interconnected systems. We proposethe concept of “emergent centralisation” to describe situations where a single systembecomes critically important for the functioning of the whole ecosystem, and arguethat such situations are likely to become more and more frequent in interconnectedsocio-technical systems. We anticipate that the systemic approach we propose willhave implications for future assessments of trustless systems and call for the attentionof policy-makers on the fragility of our interconnected and rapidly changing world
Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.
BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721
Quantum physics in inertial and gravitational fields
Covariant generalizations of well-known wave equations predict the existence
of inertial-gravitational effects for a variety of quantum systems that range
from Bose-Einstein condensates to particles in accelerators. Additional effects
arise in models that incorporate Born reciprocity principle and the notion of a
maximal acceleration. Some specific examples are discussed in detail.Comment: 25 pages,1 figure,to appear in "Relativity in Rotating Frame
Profiling of the perturbed metabolomic state of mouse spleen during acute and chronic toxoplasmosis
Background
Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases. Given the parasite ability to influence host immunity and metabolism, understanding of the metabolic alterations in the host’s immune organs during T. gondii infection may enhance the understanding of the molecular mechanisms that define the pathophysiology of T. gondii infection.
Methods
We investigated the global metabolic changes in the spleen of BALB/c mice at early and late stage of infection with T. gondii using LC-MS/MS-based metabolomics. Multivariate data analysis methods, principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were used to identify metabolites that are influenced by T. gondii infection.
Results
Multivariate analyses clearly separated the metabolites of spleen of infected and control mice. A total of 132 differential metabolites were identified, 23 metabolites from acutely infected versus control mice and 109 metabolites from chronically infected versus control mice. Lipids, hormones, lactones, acids, peptides, antibiotics, alkaloids and natural toxins were the most influenced chemical groups. There were 12 shared differential metabolites between acutely infected versus control mice and chronically infected versus control mice, of which 4,4-Dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol was significantly upregulated and ubiquinone-8 was significantly downregulated. Major perturbed metabolic pathways included primary bile acid biosynthesis, steroid hormone biosynthesis, biotin metabolism, and steroid biosynthesis, with arachidonic acid metabolism being the most significantly impacted pathway. These metabolic changes suggest a multifactorial nature of the immunometabolic responses of mouse spleen to T. gondii infection.
Conclusions
This study demonstrated that T. gondii infection can cause significant metabolomic alterations in the spleen of infected mice. These findings provide new insights into the molecular mechanisms that underpin the pathogenesis of T. gondii infection
Higgs boson production in photon-photon collision at ILC: a comparative study in different little Higgs models
We study the process \gamma\gamma->h->bb_bar at ILC as a probe of different
little Higgs models, including the simplest little Higgs model (SLH), the
littlest Higgs model (LH), and two types of littlest Higgs models with T-parity
(LHT-I, LHT-II). Compared with the Standard Model (SM) prediction, the
production rate is found to be sizably altered in these little Higgs models
and, more interestingly, different models give different predictions. We find
that the production rate can be possibly enhanced only in the LHT-II for some
part of the parameter space, while in all other cases the rate is suppressed.
The suppression can be 10% in the LH and as much as 60% in both the SLH and the
LHT-I/LHT-II. The severe suppression in the SLH happens for a large \tan\beta
and a small m_h, in which the new decay mode h->\eta\eta (\eta is a light
pseudo-scalar) is dominant; while for the LHT-I/LHT-II the large suppression
occurs when f and m_h are both small so that the new decay mode h->A_H A_H is
dominant. Therefore, the precision measurement of such a production process at
the ILC will allow for a test of these models and even distinguish between
different scenarios.Comment: Version in JHEP (h-g-g & h-gamma-gamma expressions added
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