54 research outputs found
Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity
DNA Dynamics Is Likely to Be a Factor in the Genomic Nucleotide Repeats Expansions Related to Diseases
Trinucleotide repeats sequences (TRS) represent a common type of genomic DNA
motif whose expansion is associated with a large number of human diseases. The
driving molecular mechanisms of the TRS ongoing dynamic expansion across
generations and within tissues and its influence on genomic DNA functions are
not well understood. Here we report results for a novel and notable collective
breathing behavior of genomic DNA of tandem TRS, leading to propensity for large
local DNA transient openings at physiological temperature. Our Langevin
molecular dynamics (LMD) and Markov Chain Monte Carlo (MCMC) simulations
demonstrate that the patterns of openings of various TRSs depend specifically on
their length. The collective propensity for DNA strand separation of repeated
sequences serves as a precursor for outsized intermediate bubble states
independently of the G/C-content. We report that repeats have the potential to
interfere with the binding of transcription factors to their consensus sequence
by altered DNA breathing dynamics in proximity of the binding sites. These
observations might influence ongoing attempts to use LMD and MCMC simulations
for TRS–related modeling of genomic DNA functionality in elucidating the
common denominators of the dynamic TRS expansion mutation with potential
therapeutic applications
A thioacetamide-induced hepatic encephalopathy model in C57BL/6 mice: a behavioral and neurochemical study
Metformin mitigates the impaired development of skeletal muscle in the offspring of obese mice
Background: Maternal obesity is linked with offspring obesity and type 2 diabetes. Skeletal muscle (SM) insulin resistance is central to the development of diabetes. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is inhibited in SM of fetuses born to obese mothers
The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells
The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNα treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2α and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNα combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug
Renal ageing: Changes in the cellular mechanism of energy metabolism and oxidant handling (Review Article)
Would you mind forking this process? A denial of service attack on Android (and some countermeasures
We present a previously undisclosed vulnerability of Android OS which can be exploited by mounting a Denial-of-Service attack that makes devices become totally unresponsive. We discuss the characteristics of the vulnerability – which affects all versions of Android – and propose two different fixes, each involving little patching implementing a few architectural countermeasures. We also provide experimental evidence of the effectiveness of the exploit as well as of the proposed countermeasures.
Intrusion-Resilience via the Bounded-Storage Model
We introduce a new method of achieving intrusion-resilience in the cryptographic protocols. More precisely we show how to preserve security of such protocols, even if a malicious program (e.g. a virus) was installed on a computer of an honest user (and it was later removed). The security of our protocols relies on the assumption that the amount of data that the adversary can transfer from the infected machine is limited (however, we allow the adversary to perform any efficient computation on user's private data, before deciding on what to transfer). We focus on two cryptographic tasks, namely: authenticated key exchange and entity authentication. Our method is based on the results from the Bounded-Storage Model
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