University of Minnesota

About: University of Minnesota is a education organization based out in Minneapolis, Minnesota, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 117432 authors who have published 257986 publications receiving 11944239 citations. The organization is also known as: University of Minnesota, Twin Cities & University of Minnesota-Twin Cities.

Detection of microRNA Expression in Human Peripheral Blood Microvesicles

Abstract: Background: MicroRNAs (miRNA) are small non-coding RNAs that regulate translation of mRNA and protein. Loss or enhanced expression of miRNAs is associated with several diseases, including cancer. However, the identification of circulating miRNA in healthy donors is not well characterized. Microvesicles, also known as exosomes or microparticles, circulate in the peripheral blood and can stimulate cellular signaling. In this study, we hypothesized that under normal healthy conditions, microvesicles contain miRNAs, contributing to biological homeostasis. Methodology/Principal Findings: Microvesicles were isolated from the plasma of normal healthy individuals. RNA was isolated from both the microvesicles and matched mononuclear cells and profiled for 420 known mature miRNAs by realtime PCR. Hierarchical clustering of the data sets indicated significant differences in miRNA expression between peripheral blood mononuclear cells (PBMC) and plasma microvesicles. We observed 71 miRNAs co-expressed between microvesicles and PBMC. Notably, we found 33 and 4 significantly differentially expressed miRNAs in the plasma microvesicles and mononuclear cells, respectively. Prediction of the gene targets and associated biological pathways regulated by the detected miRNAs was performed. The majority of the miRNAs expressed in the microvesicles from the blood were predicted to regulate cellular differentiation of blood cells and metabolic pathways. Interestingly, a select few miRNAs were also predicted to be important modulators of immune function. Conclusions: This study is the first to identify and define miRNA expression in circulating plasma microvesicles of normal subjects. The data generated from this study provides a basis for future studies to determine the predictive role of peripheral blood miRNA signatures in human disease and will enable the definition of the biological processes regulated by these miRNA.

Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes

Abstract: Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (P52) genes1. The mutant APPK670N,M67M transgenic line, Tg2576, shows markedly elevated amyloid β-protein (AP) levels at an early age and, by 9–12 months, develops extracellular AD-type Ap deposits in the cortex and hippocampus2. Mutant PS1 transgenic mice do not show abnormal pathology, but do display subtly elevated levels of the highly amyloidogenic 42- or 43-amino acid peptide Aβ342(43) (ref. 3). Here we demonstrate that the doubly transgenic progeny from a cross between line Tg2576 and a mutant PS1M46L transgenic line develop large numbers of fibrillar Aβ deposits in cerebral cortex and hippocampus far earlier than their singly transgenic Tg2576 litter-mates. In the period preceding overt Aβ deposition, the doubly transgenic mice show a selective 41% increase in Aβ42(43) in their brains. Thus, the development of AD-like pathology is substantially enhanced when a P51 mutation, which causes a modest increase in Aβ42(43), is introduced into Tg2576-derived mice. Remarkably, both doubly and singly transgenic mice showed reduced spontaneous alternation performance in a “Y” maze before substantial Aβ deposition was apparent. This suggests that some aspects of the behavioral phenotype in these mice may be related to an event that precedes plaque formation.

A simple and general parameterization quantifying performance in fading channels

Abstract: We quantify the performance of wireless transmissions over random fading channels at high signal-to-noise ratio (SNR). The performance criteria we consider are average probability of:error and outage probability. We show that as functions of the average SNR, they can both be characterized by two parameters: the diversity and coding gains. They both exhibit identical diversity orders, but their coding gains in decibels differ by a constant. The diversity and coding gains are found to depend on the behavior of-the random SNR's probability density function only at the origin, or equivalently, on the decaying order of the corresponding moment generating function (i.e., how fast the moment generating function goes to zero as its argument goes to infinity). Diversity and coding gains for diversity combining systems are expressed in terms of the diversity branches' individual diversity and coding gains, where the branches can come from any diversity technique such as space, time, frequency, or, multipath. The proposed analysis offers a simple and unifying approach to evaluating the performance of uncoded and (possibly space-time) coded transmissions over fading channels, and the method applies to almost all digital modulation schemes, including M-ary phaseshift keying, quadrature amplitude modulation, and frequency-shift keying with coherent or noncoherent detection.

Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement

Abstract: Description: Update of the 2002 U. S. Preventive Services Task Force (USPSTF) recommendation statement on screening for breast cancer in the general population. Methods: The USPSTF examined the evidence on the efficacy of 5 screening modalities in reducing mortality from breast cancer: film mammography, clinical breast examination, breast self-examination, digital mammography, and magnetic resonance imaging in order to update the 2002 recommendation. To accomplish this update, the USPSTF commissioned 2 studies: 1) a targeted systematic evidence review of 6 selected questions relating to benefits and harms of screening, and 2) a decision analysis that used population modeling techniques to compare the expected health outcomes and resource requirements of starting and ending mammography screening at different ages and using annual versus biennial screening intervals. Recommendations: The USPSTF recommends against routine screening mammography in women aged 40 to 49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient's values regarding specific benefits and harms. (Grade C recommendation) The USPSTF recommends biennial screening mammography for women between the ages of 50 and 74 years. (Grade B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of clinical breast examination beyond screening mammography in women 40 years or older. (I statement) The USPSTF recommends against clinicians teaching women how to perform breast self-examination. (Grade D recommendation) The USPSTF concludes that the current evidence is insufficient to assess additional benefits and harms of either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer. (I statement)

Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis

Abstract: Summary Background Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. Methods We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. Findings We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8–6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500–340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600–282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600–193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400–234 300), with 135 900 (75%; [95% CI 93 900–163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10–19). Interpretation Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. Funding None.