265 research outputs found

    The Christian Orthodox Church Fasting Diet Is Associated with Lower Levels of Depression and Anxiety and a Better Cognitive Performance in Middle Life.

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    Lifestyle choices significantly influence mental health in later life. In this study we investigated the effects of the Christian Orthodox Church (COC) fasting diet, which includes long-term regular abstinence from animal-based products for half the calendar year, on cognitive function and emotional wellbeing of healthy adults. Two groups of fasting and non-fasting individuals were evaluated regarding their cognitive performance and the presence of anxiety and depression using the Mini Mental Examination Scale, the Hamilton Anxiety Scale, and the Geriatric Depression Scale (GDS), respectively. Data on physical activity, smoking, and vitamin levels were collected and correlated with mental health scoring. Negative binomial regression was performed to examine differences in the GDS scores between the two groups. Significantly lower levels of anxiety (7.48 ± 4.98 vs. 9.71 ± 5.25; p < 0.001) and depression (2.24 ± 1.77 vs. 3.5 ± 2.52; p < 0.001), along with better cognitive function (29.15 ± 0.79 vs. 28.64 ± 1.27; p < 0.001), were noticed in fasting compared to non-fasting individuals. GDS score was 31% lower (Incidence Rate Ratio: 0.69, 95% Confidence Interval: 0.56-0.85) in the fasting group compared to the control, while vitamin and ferrum levels did not differ. The COC fasting diet was found to have an independent positive impact on cognition and mood in middle-aged and elderly individuals

    Re-evaluating microglia expression profiles using RiboTag and cell isolation strategies

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    Transcriptome profiling is widely used to infer functional states of specific cell types, as well as their responses to stimuli, to define contributions to physiology and pathophysiology. Focusing on microglia, the brain’s macrophages, we report here a side-by-side comparison of classical cell-sorting-based transcriptome sequencing and the ‘RiboTag’ method, which avoids cell retrieval from tissue context and yields translatome sequencing information. Conventional whole-cell microglial transcriptomes were found to be significantly tainted by artifacts introduced by tissue dissociation, cargo contamination and transcripts sequestered from ribosomes. Conversely, our data highlight the added value of RiboTag profiling for assessing the lineage accuracy of Cre recombinase expression in transgenic mice. Collectively, this study indicates method-based biases, reveals observer effects and establishes RiboTag-based translatome profiling as a valuable complement to standard sorting-based profiling strategies

    Optimisation of Biochemical Condition and Substrates In Vitro for Tissue Engineering of Ligament

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    In this work, we analysed the effect of growth factors on in vitro cell proliferation and collagens synthesis by fibroblasts cultured for 72 h on different substrates (silicon sheet with or without 1% gelatin, and glass as control surface) for ligament tissue engineering. A human fibroblast cell line (CRL-2703) was used. The synthesis of type I and type III collagens were evaluated qualitatively and quantitatively by RT-PCR and confocal microscopy, respectively. Cell proliferation was evaluated by two methods: (1) MTT assay (2) cell cycle analysis. It was found that PDGF-AB stimulate the proliferation of fibroblast cultured on gelatin coated silicon sheet in dose dependant manner with a maximum effect at 10 ng ml(−1). The exogenous TGF-β1 induced the expression of type I and type III collagens in a dose and substrate-dependant manner. We deduce from this work that biochemical conditions and substrates have an important impact for optimisation of the tissue neo synthesis

    Dicer Deficiency Differentially Impacts Microglia of the Developing and Adult Brain

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    Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge. After peripheral endotoxin exposure, Dicer-deficient microglia expressed more pro-inflammatory cytokines than wild-type microglia and thereby compromised hippocampal neuronal functions. In contrast, prenatal Dicer ablation resulted in spontaneous microglia activation and revealed a role for Dicer in DNA repair and preservation of genome integrity. Accordingly, Dicer deficiency rendered otherwise radio-resistant microglia sensitive to gamma irradiation. Collectively, the differential impact of the Dicer ablation on microglia of the developing and adult brain highlights the changes these cells undergo with time

    Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity

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    Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent

    TBC1D3, a Hominoid-Specific Gene, Delays IRS-1 Degradation and Promotes Insulin Signaling by Modulating p70 S6 Kinase Activity

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    Insulin/IGF-1 signaling plays a pivotal role in the regulation of cellular homeostasis through its control of glucose metabolism as well as due to its effects on cell proliferation. Aberrant regulation of insulin signaling has been repeatedly implicated in uncontrolled cell growth and malignant transformations. TBC1D3 is a hominoid specific gene previously identified as an oncogene in breast and prostate cancers. Our efforts to identify the molecular mechanisms of TBC1D3-induced oncogenesis revealed the role of TBC1D3 in insulin/IGF-1 signaling pathway. We document here that TBC1D3 intensifies insulin/IGF-1-induced signal transduction through intricate, yet elegant fine-tuning of signaling mechanisms. We show that TBC1D3 expression substantially delayed ubiquitination and degradation of insulin receptor substrate-1 (IRS-1). This effect is achieved through suppression of serine phosphorylation at S636/639, S307 and S312 of IRS-1, which are key phosphorylation sites required for IRS-1 degradation. Furthermore, we report that the effect of TBC1D3 on IRS-1:S636/639 phosphorylation is mediated through TBC1D3-induced activation of protein phosphatase 2A (PP2A), followed by suppression of T389 phosphorylation on p70 S6 kinase (S6K). TBC1D3 specifically interacts with PP2A regulatory subunit B56γ, indicating that TBC1D3 and PP2A B56γ operate jointly to promote S6K:T389 dephosphorylation. These findings suggest that TBC1D3 plays an unanticipated and potentially unique role in the fine-tuning of insulin/IGF-1 signaling, while providing novel insights into the regulation of tumorigenesis by a hominoid-specific protein

    Provable Security Evaluation of Structures against Impossible Differential and Zero Correlation Linear Cryptanalysis

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    Impossible differential and zero correlation linear cryptanalysis are two of the most important cryptanalytic vectors. To characterize the impossible differentials and zero correlation linear hulls which are independent of the choices of the non-linear components, Sun et al. proposed the structure deduced by a block cipher at CRYPTO 2015. Based on that, we concentrate in this paper on the security of the SPN structure and Feistel structure with SP-type round functions. Firstly, we prove that for an SPN structure, if \alpha_1\rightarrow\beta_1 and \alpha_2\rightarrow\beta_ are possible differentials, \alpha_1|\alpha_2\rightarrow\beta_1|\beta_2 is also a possible differential, i.e., the OR | operation preserves differentials. Secondly, we show that for an SPN structure, there exists an r-round impossible differential if and only if there exists an r-round impossible differential \alpha\not\rightarrow\beta where the Hamming weights of both \alpha and \beta are 1. Thus for an SPN structure operating on m bytes, the computation complexity for deciding whether there exists an impossible differential can be reduced from O(2^{2m}) to O(m^2). Thirdly, we associate a primitive index with the linear layers of SPN structures. Based on the matrices theory over integer rings, we prove that the length of impossible differentials of an SPN structure is upper bounded by the primitive index of the linear layers. As a result we show that, unless the details of the S-boxes are considered, there do not exist 5-round impossible differentials for the AES and ARIA. Lastly, based on the links between impossible differential and zero correlation linear hull, we projected these results on impossible differentials to zero correlation linear hulls. It is interesting to note some of our results also apply to the Feistel structures with SP-type round functions

    DLCT: A New Tool for Differential-Linear Cryptanalysis

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    Differential cryptanalysis and linear cryptanalysis are the two best-known techniques for cryptanalysis of block ciphers. In 1994, Langford and Hellman introduced the differential-linear (DL) attack based on dividing the attacked cipher EE into two subciphers E0E_0 and E1E_1 and combining a differential characteristic for E0E_0 with a linear approximation for E1E_1 into an attack on the entire cipher EE. The DL technique was used to mount the best known attacks against numerous ciphers, including the AES finalist Serpent, ICEPOLE, COCONUT98, Chaskey, CTC2, and 8-round DES. Several papers aimed at formalizing the DL attack, and formulating assumptions under which its complexity can be estimated accurately. These culminated in a recent work of Blondeau, Leander, and Nyberg (Journal of Cryptology, 2017) which obtained an accurate expression under the sole assumption that the two subciphers E0E_0 and E1E_1 are independent. In this paper we show that in many cases, dependency between the two subcipher s significantly affects the complexity of the DL attack, and in particular, can be exploited by the adversary to make the attack more efficient. We present the Differential-Linear Connectivity Table (DLCT) which allows us to take into account the dependency between the two subciphers, and to choose the differential characteristic in E0E_0 and the linear approximation in E1E_1 in a way that takes advantage of this dependency. We then show that the DLCT can be constructed efficiently using the Fast Fourier Transform. Finally, we demonstrate the strength of the DLCT by using it to improve differential-linear attacks on ICEPOLE and on 8-round DES, and to explain published experimental results on Serpent and on the CAESAR finalist Ascon which did not comply with the standard differential-linear framework

    Anomalies and Vector Space Search: Tools for S-Box Analysis

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    International audienceS-boxes are functions with an input so small that the simplest way to specify them is their lookup table (LUT). How can we quantify the distance between the behavior of a given S-box and that of an S-box picked uniformly at random? To answer this question, we introduce various "anomalies". These real numbers are such that a property with an anomaly equal to should be found roughly once in a set of 2a2^a random S-boxes. First, we present statistical anomalies based on the distribution of the coefficients in the difference distribution table, linear approximation table, and for the first time, the boomerang connectivity table. We then count the number of S-boxes that have block-cipher like structures to estimate the anomaly associated to those. In order to recover these structures, we show that the most general tool for decomposing S-boxes is an algorithm efficiently listing all the vector spaces of a given dimension contained in a given set, and we present such an algorithm. Combining these approaches, we conclude that all permutations that are actually picked uniformly at random always have essentially the same cryptographic properties and the same lack of structure
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