Effect of FTY720 on Some Physiological Indexes of Non-Obese Diabetic (NOD) Mice

The studies were performed to investigate the physiological characteristics of non-obese diabetic (NOD) mice treated with FTY720. At the age of 12 weeks, each mouse was fed with FTY720 or physiological saline once a day for 10 weeks running, and their blood glucose, weight, anti-GAD antibody and organ indexes were determined. No mouse in group FTY720 (NOD mice treated with FTY720) showed diabetic symptoms. The average content of serum anti-GAD antibody in group FTY720 decreased 48.75% (P < 0.01). It was concluded that the spleen, kidney and liver of NOD mice treated with FTY720 shriveled significantly in the progression of diabetes (P < 0.01 or P < 0.05). The body weight of group FTY720 mice was slightly lower than that of the model control (MC) group and these two groups both had less body weight than the normal control (NC) group (P < 0.01). The result of tests of anti-GAD antibody suggested that FTY720 treatment could suppress the anti-GAD response

Serum vitamin levels in multiple system atrophy: A case-control study

AimThere is increasing evidence suggesting that vitamins may play important roles in the pathogenesis of multiple system atrophy (MSA). The purpose of this study was to detect the changes of serum vitamin levels and investigate their correlation with disease severity in MSA patients.MethodsIn this cross-sectional study, 244 MSA patients, 200 Parkinson’s disease (PD) patients and 244 age-gender matched healthy controls were recruited. Serum vitamin levels were measured, including vitamin A, B1, B2, B9 (folate), B12, C, D, and E. Relevant clinical scales were used to assess the disease severity of MSA patients.ResultsCompared with the healthy controls, decreased serum folate levels and increased serum vitamin A and C levels were detected in MSA patients. Similar differences were also observed in the gender-based subgroup analysis. There were no differences detected between MSA and PD patients. In MSA patients, significant correlation was found between vitamin A, folate, or vitamin C and relevant clinical scales or laboratory findings. In addition, ROC analysis showed potential diagnostic value of the combination of vitamin A, folate, and vitamin C in distinguishing MSA patients from healthy controls.ConclusionThere were significant changes in the blood vitamin spectrums of MSA patients, suggesting that dysregulation of vitamins homeostasis might play an important role in the pathogenesis of MSA

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

The CEP5 Peptide Promotes Abiotic Stress Tolerance, As Revealed by Quantitative Proteomics, and Attenuates the AUX/IAA Equilibrium in Arabidopsis.

Peptides derived from non-functional precursors play important roles in various developmental processes, but also in (a)biotic stress signaling. Our (phospho)proteome-wide analyses of C-TERMINALLY ENCODED PEPTIDE 5 (CEP5)-mediated changes revealed an impact on abiotic stress-related processes. Drought has a dramatic impact on plant growth, development and reproduction, and the plant hormone auxin plays a role in drought responses. Our genetic, physiological, biochemical, and pharmacological results demonstrated that CEP5-mediated signaling is relevant for osmotic and drought stress tolerance in Arabidopsis, and that CEP5 specifically counteracts auxin effects. Specifically, we found that CEP5 signaling stabilizes AUX/IAA transcriptional repressors, suggesting the existence of a novel peptide-dependent control mechanism that tunes auxin signaling. These observations align with the recently described role of AUX/IAAs in stress tolerance and provide a novel role for CEP5 in osmotic and drought stress tolerance

The mixed Lp affine surface areas for functions

In this paper, we propose a definition of a general mixed Lp affine surface area, -n ≠ p ∈ ℝ, for multiple functions. Our denfiition is different from and is "dual" to the one in [11] by Caglar and Ye. In particular, our denfiition makes it possible to establish an integral formula for the general mixed Lp affine surface area of multiple functions (see Theorem 3.1 for more precise statements). Properties of the newly introduced functional are proved such as affine invariance, and related affine isoperimetric inequalities are proved.Mathematics Subject Classification (2010): 52A20, 53A15.Keywords: Affine isoperimetric inequality, affine surface area, functional inequality, Lp affine surface area, Lp geominimal surface area, Blaschke-Santaló inequalit

On k-Mer-Based and Maximum Likelihood Estimation Algorithms for Trace Reconstruction

The goal of the trace reconstruction problem is to recover a string $x\in\{0,1\}^n$ given many independent {\em traces} of $x$, where a trace is a subsequence obtained from deleting bits of $x$ independently with some given probability $p\in [0,1).$ A recent result of Chase (STOC 2021) shows how $x$ can be determined (in exponential time) from $\exp(\widetilde{O}(n^{1/5}))$ traces. This is the state-of-the-art result on the sample complexity of trace reconstruction. In this paper we consider two kinds of algorithms for the trace reconstruction problem. Our first, and technically more involved, result shows that any $k$-mer-based algorithm for trace reconstruction must use $\exp(\Omega(n^{1/5}))$ traces, under the assumption that the estimator requires $poly(2^k, 1/\varepsilon)$ traces, thus establishing the optimality of this number of traces. The analysis of this result also shows that the analysis technique used by Chase (STOC 2021) is essentially tight, and hence new techniques are needed in order to improve the worst-case upper bound. Our second, simple, result considers the performance of the Maximum Likelihood Estimator (MLE), which specifically picks the source string that has the maximum likelihood to generate the samples (traces). We show that the MLE algorithm uses a nearly optimal number of traces, \ie, up to a factor of $n$ in the number of samples needed for an optimal algorithm, and show that this factor of $n$ loss may be necessary under general ``model estimation'' settings