464 research outputs found
APOE4 allele-specific associations between diet, multimodal biomarkers, and cognition among Puerto Rican adults in Massachusetts
BackgroundApolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimerâs Disease (AD), and the Îľ4 allele (APOE4) may interact with lifestyle factors that relate to brain structural changes, underlying the increased risk of AD. However, the exact role of APOE4 in mediating interactions between the peripheral circulatory system and the central nervous system, and how it may link to brain and cognitive aging requires further elucidation. In this analysis, we investigated the association between APOE4 carrier status and multimodal biomarkers (diet, blood markers, clinical diagnosis, brain structure, and cognition) in the context of geneâenvironment interactions.MethodsParticipants were older adults from a longitudinal observational study, the Boston Puerto Rican Health Study (BPRHS), who self-identified as of Puerto Rican descent. Demographics, APOE genotype, diet, blood, and clinical data were collected at baseline and at approximately 12th year, with the addition of multimodal brain magnetic resonance imaging (MRI) (T1-weighted and diffusion) and cognitive testing acquired at 12-year. Measures were compared between APOE4 carriers and non-carriers, and associations between multimodal variables were examined using correlation and multivariate network analyses within each group.ResultsA total of 156 BPRHS participants (mean age at imagingâ=â68âyears, 77% female, mean follow-up 12.7âyears) with complete multimodal data were included in the current analysis. APOE4 carriers (nâ=â43) showed reduced medial temporal lobe (MTL) white matter (WM) microstructural integrity and lower mini-mental state examination (MMSE) score than non-carriers (nâ=â113). This pattern was consistent with an independent sample from the Alzheimerâs Disease Neuroimaging Initiative (ADNI) of nâ=â283 non-Hispanic White adults without dementia (mean ageâ=â75, 40% female). Within BPRHS, carriers showed distinct connectivity patterns between multimodal biomarkers, characterized by stronger direct network connections between baseline diet/blood markers with 12-year blood/clinical measures, and between blood markers (especially lipids and cytokines) and WM. Cardiovascular burden (i.e., hypertension and diabetes status) was associated with WM integrity for both carriers and non-carriers.ConclusionAPOE4 carrier status affects interactions between dietary factors, multimodal blood biomarkers, and MTL WM integrity across ~12âyears of follow-up, which may reflect increased peripheral-central systems crosstalk following bloodâbrain barrier breakdown in carriers
Radiative Two Loop Inverse Seesaw and Dark Matter
Seesaw mechanism provides a natural explanation of light neutrino masses
through suppression of heavy seesaw scale. In inverse seesaw models the seesaw
scale can be much lower than that in the usual seesaw models. If terms inducing
seesaw masses are further induced by loop corrections, the seesaw scale can be
lowered to be in the range probed by experiments at the LHC without fine
tuning. In this paper we construct models in which inverse seesaw neutrino
masses are generated at two loop level. These models also naturally have dark
matter candidates. Although the recent data from Xenon100 put stringent
constraint on the models, they can be consistent with data on neutrino masses,
mixing, dark matter relic density and direct detection. These models also have
some interesting experimental signatures for collider and flavor physics.Comment: RevTex 14 pages 3 figures. Several references adde
Multilayer regulatory mechanisms control cleavage factor I proteins in filamentous fungi
Cleavage factor I (CFI) proteins are core components of the polyadenylation machinery that can regulate several steps of mRNA life cycle, including alternative polyadenylation, splicing, export and decay. Here, we describe the regulatory mechanisms that control two fungal CFI protein classes in Magnaporthe oryzae: Rbp35/CfI25 complex and Hrp1. Using mutational, genetic and biochemical studies we demonstrate that cellular concentration of CFI mRNAs is a limited indicator of their protein abundance. Our results suggest that several post-transcriptional mechanisms regulate Rbp35/CfI25 complex and Hrp1 in the rice blast fungus, some of which are also conserved in other ascomycetes. With respect to Rbp35, these include C-terminal processing, RGG-dependent localization and cleavage, C-terminal autoregulatory domain and regulation by an upstream open reading frame of Rbp35-dependent TOR signalling pathway. Our proteomic analyses suggest that Rbp35 regulates the levels of proteins involved in melanin and phenylpropanoids synthesis, among others. The drastic reduction of fungal CFI proteins in carbon-starved cells suggests that the pre-mRNA processing pathway is altered. Our findings uncover broad and multilayer regulatory mechanisms controlling fungal polyadenylation factors, which have profound implications in pre-mRNA maturation. This area of research offers new avenues for fungicide design by targeting fungal-specific proteins that globally affect thousands of mRNAs
Integrated syphilis/HIV screening in China: a qualitative analysis
<p>Abstract</p> <p>Background</p> <p>The last decade has seen enormous advances in HIV treatment and care, but how to implement scaled up HIV testing, prevention, and treatment in low-income areas still presents a formidable public health challenge. South China faces expanding syphilis and sexually transmitted HIV epidemics, but health systems characteristics important for scaling up syphilis and HIV testing have not been defined.</p> <p>Methods</p> <p>A purposive sample to ensure public, private, and public-private hybrid STI clinic inclusion was selected in a South China city. Eight key informant interviews were conducted with the STI clinic manager, followed by eight focus group discussions with physicians. Data collection relied on a semi-structured format that included questions in each of the following domains: 1) clinical facilities; 2) laboratory capacity with a focus on syphilis/HIV diagnosis; 3) clinic personnel; 4) physical space with a focus on locations to disclose confidential results; 5) financial support.</p> <p>Results</p> <p>Public STI clinics had free syphilis testing/treatment and laboratory facilities to perform essential syphilis and HIV tests. However, despite serving a large number of STI patients, private STI clinics lacked nontreponemal syphilis testing, HIV testing, and had fewer connections to the public health infrastructure. Formally trained assistant physicians were 2.5 times as common as physicians at STI clinics. Only one of the 8 sites had onsite voluntary counseling and testing (VCT) services available.</p> <p>Conclusion</p> <p>These STI case studies reveal the potential for expanding integrated syphilis/HIV services at public STI clinics in China. More health services research is needed to guide scale-up of syphilis/HIV testing in China.</p
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Evolutionary development of the plant and spore wall
The article provides an overview of the development and structure of spore and pollen walls in the major plant groups and summarises progress in our understanding of the molecular genetics underpinning spore/pollen evolution and development
Integrin β1 is required for the invasive behaviour but not proliferation of squamous cell carcinoma cells in vivo
Integrin β1 is both overexpressed and in an âactive' conformation in vulval squamous cell carcinomas (VSCCs) compared to matched normal skin. To investigate the significance of integrin β1 deregulation we stably knocked-down integrin β1 expression in the VSCC cell line A431. In vitro analysis revealed that integrin β1 is required for cell adhesion, cell spreading and invasion. However, integrin β1 is not required for cell growth or activation of FAK and ERK signalling in vitro or in vivo. Strikingly, while control tumours were able to invade the dermis, integrin β1 knockdown tumours were significantly more encapsulated and less invasive
Performance and Operation of the CMS Electromagnetic Calorimeter
The operation and general performance of the CMS electromagnetic calorimeter
using cosmic-ray muons are described. These muons were recorded after the
closure of the CMS detector in late 2008. The calorimeter is made of lead
tungstate crystals and the overall status of the 75848 channels corresponding
to the barrel and endcap detectors is reported. The stability of crucial
operational parameters, such as high voltage, temperature and electronic noise,
is summarised and the performance of the light monitoring system is presented
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