From Complexity to Algebra and Back: Digraph Classes, Collapsibility, and the PGP

Inspired by computational complexity results for the quantified constraint satisfaction problem, we study the clones of idem potent polymorphisms of certain digraph classes. Our first results are two algebraic dichotomy, even "gap", theorems. Building on and extending [Martin CP'11], we prove that partially reflexive paths bequeath a set of idem potent polymorphisms whose associated clone algebra has: either the polynomially generated powers property (PGP), or the exponentially generated powers property (EGP). Similarly, we build on [DaMM ICALP'14] to prove that semi complete digraphs have the same property. These gap theorems are further motivated by new evidence that PGP could be the algebraic explanation that a QCSP is in NP even for unbounded alternation. Along the way we also effect a study of a concrete form of PGP known as collapsibility, tying together the algebraic and structural threads from [Chen Sicomp'08], and show that collapsibility is equivalent to its Pi2-restriction. We also give a decision procedure for k-collapsibility from a singleton source of a finite structure (a form of collapsibility which covers all known examples of PGP for finite structures). Finally, we present a new QCSP trichotomy result, for partially reflexive paths with constants. Without constants it is known these QCSPs are either in NL or Pspace-complete [Martin CP'11], but we prove that with constants they attain the three complexities NL, NP-complete and Pspace-complete

Luminal Ca2+ depletion during the unfolded protein response in Xenopus oocytes: Cause and consequence

The endoplasmic reticulum (ER) is a Ca2+ storing organelle that plays a critical role in the synthesis, folding and post-translational modifications of many proteins. The ER enters into a condition of stress when the load of newly synthesized proteins exceeds its folding and processing capacity. This activates a signal transduction pathway called the unfolded protein response (UPR) that attempts to restore homeostasis. The precise role of ER Ca2+ in the initiation of the UPR has not been defined. Specifically, it has not been established whether ER Ca2+ dysregulation is a cause or consequence of ER stress. Here, we report that partial depletion of ER Ca2+ stores induces a significant induction of the UPR, and leads to the retention of a normally secreted protein Carboxypeptidase Y. Moreover, inhibition of protein glycosylation by tunicamycin rapidly induced an ER Ca2+ leak into the cytosol. However, blockade of the translocon with emetine inhibited the tunicamycin-induced Ca2+ release. Furthermore, emetine treatment blocked elF2α phosphorylation and reduced expression of the chaperone BiP. These findings suggest that Ca2+ may be both a cause and a consequence of ER protein misfolding. Thus, it appears that ER Ca2+ leak is a significant co-factor for the initiation of the UPR.Fil: Paredes, R. Madelaine. University of Texas; Estados UnidosFil: Bollo, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Holstein, Deborah. University of Texas; Estados UnidosFil: Lechleiter, James D.. University of Texas; Estados Unido

Did Ebola emerge in West Africa by a policy-driven phase change in agroecology? Ebola's social context

SCOPUS: no.jinfo:eu-repo/semantics/publishe

Phosphatase Rtr1 Regulates Global Levels of Serine 5 RNA Polymerase II C-Terminal Domain Phosphorylation and Cotranscriptional Histone Methylation

In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1 Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes

High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS) that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes

High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS) that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes

The new 14C chronology for the Palaeolithic site of La Ferrassie, France: the disappearance of Neanderthals and the arrival of Homo sapiens in France

The grand abri at La Ferrassie (France) has been a key site for Palaeolithic research since the early part of the 20th century. It became the eponymous site for one variant of Middle Palaeolithic stone tools, and its sequence was used to define stages of the Aurignacian, an early phase of the Upper Palaeolithic. Several Neanderthal remains, including two relatively intact skeletons, make it one of the most important sites for the study of Neanderthal morphology and one of the more important data sets when discussing the Neanderthal treatment of the dead. However, the site has remained essentially undated. Our goal here is to provide a robust chronological framework of the La Ferrassie sequence to be used for broad regional models about human behaviour during the late Middle to Upper Palaeolithic periods. To achieve this goal, we used a combination of modern excavation methods, extensive geoarchaeological analyses, and radiocarbon dating. If we accept that Neanderthals were responsible for the Châtelperronian, then our results suggest an overlap of ca. 1600 years with the newly arrived Homo sapiens found elsewhere in France